See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/11442266

Functional circuitry of the avian basal ganglia:

implications for basal ganglia organization in
stem amniotes

Article in Brain Research Bulletin February 2002

DOI: 10.1016/S0361-9230(01)00667-0 Source: PubMed

CITATIONS READS

55 88

1 author:

Anton Reiner
The University of Tennessee Health Science Center
248 PUBLICATIONS 16,938 CITATIONS

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Long term effects of TBI View project

Drug therapy for Huntington's Disease View project

All content following this page was uploaded by Anton Reiner on 08 October 2017.

The user has requested enhancement of the downloaded file.


PII S0361-9230(01)00667-0
Functional circuitry of the avian basal ganglia:
Implications for basal ganglia organization
in stem amniotes
Anton Reiner*
Department of Anatomy and Neurobiology, University of Tennessee-Memphis, Memphis, TN, USA
ABSTRACT: Histochemical, pathway tracing, and neuropep-
tide/neurotransmitter localization studies in birds, reptiles and
mammals during the 1970s and 80s clearly showed that the
telencephalon in all amniotes consists of a prominent ventrally
situated subpallial region termed the basal ganglia, and a large
overlying region involved in higher order information process-
ing termed the pallium or cortex. These studies also showed
that the basal ganglia in all extant amniote groups possessed
neurochemically and hodologically distinct striatal and pallidal
territories. More recently, studies of the localization of genes
controlling regional brain development have confirmed the ho-
mology of the basal ganglia among amniotes. In our ongoing
studies, we have identified several aspects of the functional
organization of the basal ganglia that birds also share with
mammals. These include: (1) an extensive glutamatergic cor-
tico-striatal input and distinctive, cell-type specific localization
of glutamate receptor subtypes; (2) an extensive, presumptively
glutamatergic intralaminar thalamic input to striatal neurons; (3)
an extensive dopaminergic input from the midbrain targeting
both substance P (SP) type and enkephalin (ENK) type striatal
projection neurons, with SP-type striatal neurons seemingly
richer in the D-1 type dopamine receptor; and (4) SP and
ENK striatal outputs giving rise to functionally distinct so-
called direct and indirect motor output pathways, with the di-
rect pathway having a pallido-thalamo-motor cortex loop and
the indirect pathway relaying back to the direct circuit via the
subthalamic nucleus. These findings suggest that the major
aspects of the cellular organization and functional circuitry of
the basal ganglia in stem amniotes were already as observed in
living amniotes, as therefore presumably was its key role in
movement control. Because the organization of the basal gan-
glia of anamniotes is clearly less elaborate than in amniotes,
and because the basal ganglia and cortex in amniotes are
clearly extensively interconnected structures, it seems likely
that stem amniotes were characterized by a major step forward
in the grade of telencephalic organization of both the basal
ganglia and the pallium. 2002 Elsevier Science Inc.
KEY WORDS: Striatum, Pallidum, Birds, Mammals, Cortex, Evo-
lution.
INTRODUCTION
Histochemical studies, pathway tracing studies, and neuropeptide/
neurotransmitter localization studies in birds, reptiles, and mam-
mals during the 1970s and 80s clearly showed that the telenceph-
* Address for correspondence: Anton Reiner, Ph.D., Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee-
Memphis, 855 Monroe Avenue, Memphis, TN 38163, USA. Fax: 1-(901)-448-7193; E-mail: areiner@utmem.edu
513
Brain Research Bulletin, Vol. 57, Nos. 3/4, pp. 513528, 2002
Copyright 2002 Elsevier Science Inc.
Printed in the USA. All rights reserved
0361-9230/02/$see front matter
alon in all amniotes consists of a prominent ventrally situated
subpallial region termed the basal ganglia, and a large overlying
region involved in higher order information processing termed the
pallium [115]. These studies further showed that the basal ganglia
in amniotes typically possess a dorsal or somatic part related to
sensorimotor functions, and a ventral or visceral/limbic part related
to limbic functions. Dorsal and ventral basal ganglia are each
divided into distinct striatal and pallidal territories (Fig. 1). In the
present review we will focus on the dorsal basal ganglia, and in
using the terms basal ganglia, striatum, and pallidum it should be
taken that we are referring to the dorsal, somatic part of each.
The studies during the 70s and 80s revealed that the basal
ganglia in all extant amniotes possess a number of neurochemi-
cally distinct cell types and inputs that impart to the striatum and
pallidum histochemically unique characteristics by which they can
be recognized. For example, in all amniotes the striatal part of the
basal ganglia is rich in medium-sized neurons with spiny dendrites
[115], and it can be readily distinguished from the overlying pallial
areas because its neuropil is rich in acetylcholinesterase (AChE)
and choline acetyltransferase (CHAT), as well as in processes
containing substance P (SP), enkephalin (ENK), and dopamine
[47,64,80,84,88,94,95,112,114,115,131,149]. The abundance of
AChE in the neuropil reflects the numerous cholinergic terminals
arising from intrinsic striatal cholinergic neurons (which give rise
to a rich intrastriatal cholinergic CHAT neuropil), while the
dopaminergic terminals arise from the tegmental dopaminergic
neurons. The SP and ENK processes are the dendrites and
local axon collaterals of striatal SP and ENK neurons. The
pallidum in all amniotes contains sparsely packed large neurons
that are rich in -aminobutyric acid (GABA), its synthetic enzyme
glutamic acid decarboxylase and the neurotensin-related neuropep-
tide LANT6 [47,105,109,110,115,143], and it is distinct from the
striatum because it is rich in densely packed SP and ENK
fibers that terminate on the pallidal neurons, and relatively poor in
dopaminergic fibers and AChE [47,50,81,95,112,115,116].
More recently, studies of the localization of genes regulating
regional brain development have provided strong support for the
homologies of the tegmental dopaminergic neurons among am-
niotes and of the basal ganglia among amniotes [101,123]. Nu-
merous studies have now indicated that the brain in all vertebrates
develops in a segmental fashion [16,65,103,141], with homeobox
genes and other regulatory genes playing an important role in the
514
FIG. 1. Diagrams of frontal sections through the basal ganglia of the right telencephalic hemisphere in a
representative mammalian species (a rat) and a representative avian species (pigeon). The basal ganglia in both
consists of a striatum and a pallidum and is located in the central and/or basal telencephalon, beneath the cortical
regions. Abbreviations: AC, anterior commissure; DVR, dorsal ventricular ridge; OC, optic chiasm.
regionalization of the brain during development [18,76,123]. For
example, the nigral dopamine neurons in all amniotes, despite any
dissimilarities in their appearance and distribution, span the teg-
mental part of what has been identified as the three caudalmost of
six forebrain sectors termed prosomeres, the one mesencephalic
segment, and the one isthmic segment (as defined by various
embryological and gene expression traits) [85,100,132]. The basal
ganglia primordia (i.e., the lateral and medial ganglionic emi-
nence) in embryonic mouse are characterized by the expression of
the homeobox genes Dlx1 and Dlx2 (which are vertebrate homo-
logues of the Drosophila Distal-less gene) [18,98,99,101,123],
with the pallidal part of the basal ganglia distinguished by the
additional expression of Nkx2.1. Similarly, the region containing
the developing basal ganglia in the chick embryo specifically
expresses Dlx1/2 genes, and the pallidal field expresses Nkx2.1
[104].
AVIAN BASAL GANGLIA ORGANIZATIONINPUTS
The various studies summarized above resolved a number of
key issues about the basal ganglia in mammals, birds and reptiles.
First, they unambiguously demonstrated the location and extent of
the basal ganglia and its parts. Critical to this for birds and reptiles
was the corollary demonstration of an extensive pallial territory
within the telencephalon that had heretofore been thought by most
authors to be a portion of the basal ganglia [63,83,90,112]. Thus,
the studies of the 70s and 80s, as confirmed by the recent
molecular neuorembryology, established that the basal ganglia in
all amniotes consisted of large pallial and basal ganglia sectors
(Fig. 1). Secondly, these prior studies established that the basal
ganglia among amniotes possessed considerable similarities in
their constituent cell types and the neurochemical and hodological
identity of these cell types [94,112]. Finally, these studies showed
that the basal ganglia in all amniotes is distinguished by a striatal
sector receiving prominent input from the pallium and from the
dopaminergic neurons of the midbrain. Since the time of these
various seminal findings, we have investigated in more detail the
functional organization of the basal ganglia in birds and its simi-
larities to basal ganglia functional organization in mammals as it
REINER
has come to be understood in terms of the recent so-called direct
and indirect pathway model of basal ganglia function [1,33]. Our
goal was to determine if the structural similarities in basal ganglia
among amniotes extended to the level of functional organization
and circuitry. Our findings, as reviewed below, suggest that the
basis of the structural similarities in the basal ganglia among
amniotes is the evolutionary advancement in stem amniotes of
basal ganglia functional organization beyond that in anamniotes,
and the subsequent conservation of this organization in sauropsid
and mammalian lineages [57,115].
Cortical Input
In mammals, the cortical input to the striatum is massive and
arises from all cortical regions, including somatosensory, visual,
auditory, premotor, and motor areas [29]. In each cortical region
projecting to the striatum in mammals, two major types of corti-
costriatal projection neurons have been identified, a type that
projects to the striatum as well as other cortical regions but does
not project to the brainstem (non-pyramidal tract type) and a type
that projects to the hindbrain and the spinal cord and whose striatal
projection arises as a collateral of this descending projection
(pyramidal tract type) [29,45,153]. While it has been known for
some time that the cortex-like parts of the avian pallium project to
the striatum in birds [15,64], our recent work has shown that this
input is as extensive as the corticostriatal projection in mammals
(Fig. 2) and arises from all major parts of the pallium (i.e., the
dorsomedially situated Wulst and the more ventrolaterally situated
dorsal ventricular ridge [DVR]) [148]. Further, our work shows
that it arises from the same two major cell types as in mammalsa
pyramidal tract type neuron also projecting to brainstem and a
non-pyramidal tract type with projections limited to striatum and
other cortical areas [148]. The regions containing pyramidal
tract neurons in birds are located at the rostrodorsomedial (Wulst)
and ventrocaudolateral aspects of the telencephalic pallium (the
archistriatum, which is typically considered part of the DVR) (Fig.
3). The non-pyramidal tract neurons are located in the broad
expanse intervening between the Wulst and the archistriatum,
which we have referred to collectively as the pallium externum
AVIAN BASAL GANGLIA 515

FIG. 2. Schematic illustrations of transverse sections through the right hemisphere of the pigeon telencephalon showing the location of the striatum
and its major sources of cortical input. The striatum is shaded in black and it receives input from the striped area along the outer rind of the
pallium. This pallial region includes the hyperstriatum accessorium (HA) region of the Wulst, the pallium externum (PE) of the dorsolateral
pallium, and the archistriatum (ARCH) of the posterior basal pallium. The sections are in a rostrocaudal series (AC), and medial is to the left and
dorsal to the top in all three. Abbreviations: Dien, diencephalon; DVR, dorsal ventricular ridge; Hp, hippocampal complex; PP, paleostriatum
primitivum; S, septum.

(PE) (Fig. 3). Visceral/limbic regions such as the pyriform cortex,
the hippocampal complex, and the ventroposterior archistriatum
also contain corticostriatal projection neurons in birds, and these
regions project mainly to such visceral/limbic striatal structures as
the olfactory tubercle, the nucleus accumbens and the bed nucleus
of the stria terminalis. In contrast, the Wulst, the PE, and the
dorsointermediate archistriatum are somatic regions that contain
specialized higher order sensory or motor areas, and they mainly
project to the dorsal striatum. Thus, in terms of both its extent and
cellular origins, the corticostriatal systems of birds and mam-
mals closely resemble one another, and it is clear that in both birds
and mammals the telencephalic input must play a major role in
providing the striatum with the information needed for the role of
the basal ganglia in movement control.
To further examine the similarities between corticostriatal pro-
jection neurons in birds and mammals, we have [118] recorded
intracellularly from PE neurons, identified corticostriatal neurons
by antidromic stimulation from the ipsilateral rostral medial stri-
atum, characterized these neurons physiologically and then filled
them with biocytin. These studies show that: (1) the conduction
velocity of PE corticostriatal neurons in birds is slow (about 0.2
m/s), as in mammals; (2) the responses of avian PE corticostriatal
neurons to intracellular current pulses resemble those of mamma-
lian corticostriatal neurons; (3) avian PE corticostriatal neurons
closely resemble mammalian corticostriatal neurons in their rest-
ing membrane fluctuations and in the tendency for action poten-
tials to arise from an up state of the membrane potential; and (4)
avian corticostriatal neurons within PE resemble non-pyramidal
tract type corticostriatal neurons in mammals in that they project to
both striatum and to other regions of cortex. While avian cortico-
striatal neurons lack the apical dendrite characteristic of mamma-
lian corticostriatal neurons (and mammalian cortical pyramidal
neurons in general), they are, nonetheless, in the above major
respects similar in their behavior to mammalian corticostriatal
neurons [29].
In mammals, the striatal projection of both types of corticos-
triatal neurons ends on the dendritic spines of striatal projection
neurons, as well as on the smooth dendrites of some interneurons
[41]. The corticostriatal terminals themselves contain small round
vesicles and form asymmetric contacts with their targets, which is
characteristic of excitatory type terminals. Anatomical and physi-
ological studies have directly confirmed that the corticostriatal
system in mammals utilizes the excitatory amino acid neurotrans-
mitter glutamate [41], and the striatal target neurons of this input
have been shown to be enriched in glutamate receptors [25,26].
Our studies of the ultrastructural morphology of the corticostriatal
projection from two avian cortical regions, the Wulst and the PE,
using BDA10k revealed that the intrastriatal terminals of the
corticostriatal axons from both contain many round vesicles, and
form asymmetric synaptic contacts with spine heads and with the
dendrites of striatal neurons, suggesting that they too have an
excitatory input to striatal projection neurons [144]. Csillag et al.
[30] have directly shown by electron microscopic (EM) double-
labeling that the pyramidal tract neuron type projections from the
archistriatum to the medial striatum in chick (labeled with Phaseo-
lus vulgaris leucoagglutinin) do contain glutamate. Thus, in mam-
mals and birds both, the corticostriatal projection system appears
to be glutamatergic.
Because of the evidence that the corticostriatal input to striatum
in birds and mammals is glutamatergic, we carried out studies to
characterize the cell type-specific localization of these receptors. In
pigeons, we found by single-label light microscopic (LM) immu-
nohistochemistry that striatal projection neuron perikarya are rich
in GluR2/3 -amino-3-hydroxy-5-methyl-isoxazole-4-propionic
acid (AMPA) type subunits [145], and our prior autoradiographic
studies of MK801 binding showed the presence of N-methyl-D-
aspartate (NMDA) receptors in the avian striatum [125]. LM and
EM studies showed that while few striatal projection neuron
perikarya possessed GluR1 subunits in birds, the spines and den-
drites of the projection neurons were rich in GluR1 subunits
[145,146]. EM studies confirmed that GluR2/3 subunits are also
abundant in the dendrites and spines of striatal projection neurons
[27,146]. The localization of these AMPA subunits to dendritic
spines, the major target of the corticostriatal projection, supports
516 REINER

FIG. 3. In mammals and birds, the input to striatum arises from two main types of corticostriatal neurons: (1) neurons whose main axon projects to the
brainstem and whose striatal projection arises as a collateral off this axon; and (2) neurons that project to the striatum and various cortical areas but not
to the brainstem. Because the latter type has been shown to also project to other parts of the cortex in mammals, we will refer to it as the
intratelencephalically projecting (IT) or non-pyramidal tract (PT) type of corticostriatal neuron. The two types of corticostriatal projection neurons are
located in different sublayers of cortical layer 5 in mammals, while in birds they are segregated to different telencephalic regions. Note that PT type
neurons in birds are found in the Wulst and the archistriatum (ARCH), while IT type neurons are found in the pallium externum.

the view that the corticostriatal projection is glutamatergic. GluR4
appeared to be absent from projection neurons in birds, while
interneurons resembling the PARV/GABA interneurons were rich
in GluR1 and GluR4 subunits. The same features of NMDA and
AMPA-type glutamate receptor localization as in birds appears to
be true in turtles [38]. Our immunohistochemical double-label
studies and single-cell reverse transcription-polymerase chain re-
action (RT-PCR) in rats detected differences between projection
neurons and interneurons in AMPA receptor subunits similar to
those found in birds [25, 27,135]. In particular, we found that the
parvalbuminergic interneurons tended to be rich in the GluR1 and
GluR4 AMPA type subunits and poor in the GluR2 and GluR3
AMPA subunits, while projection neurons are rich in GluR1,
GluR2 and GluR3. EM studies revealed that, as in birds, the
majority of striatal projection neurons in rats preferentially insert
GluR1 subunits into their dendrites and spines, but not their
perikarya [25,27]. NMDA receptors are known to be abundant in
the mammalian striatum, particularly on projection neurons [26].
These various results suggest that the basic features of corti-
costriatal circuitry and the associated cell type-specific postsynap-
tic receptor mechanisms had evolved in the telencephalon as of the
stem amniotes. It is of interest that cortical inputs to the striatum
in anamniotes appear to be meager [46,78,115], and glutamate
receptors and intracellular signaling mechanisms linked to gluta-
mate receptors (such as D1-type dopamine receptor-linked and
NMDA receptor-linked phosphoprotein DARPP32) are reportedly
sparse and/or absent in the striatum in anamniotes [12,53]. Thus,
the anamnioteamniote transition appears to have been marked by
a major expansion of the cortex and the corticostriatal projec-
tion, as well as of the cellular response mechanisms associated
with this input.
Thalamic Input
In mammals and birds, a group of dorsal thalamic nuclei
projects to the striatum [20,41,49,115,147,150]. In mammals, the
major thalamic input arises from the intralaminar thalamic nuclei,
which receive sensory and motor information from diverse cortical
regions, as well as subcortical regions that include the spinal cord,
the cholinergic pedunculopontine and laterodorsal tegmental nu-
clei, the central cerebellar nuclei, the superior colliculus, the tha-
lamic reticular nucleus, and the ventral pallidum [20,49]. The
intralaminar thalamic nuclei provide a major input not only to the
striatum, but also to much of the cerebral cortex [20,21,49]. In
mammals, the intralaminar thalamic nuclei reside within a field
that also includes the mediodorsal and midline thalamic nuclear
complex (IMMC). In birds, several dorsomedial thalamic nuclei
project to the striatum and have widespread projections to cortical
areas, such as the Wulst and parts of DVR [147,150]. In birds, this
dorsomedial thalamic zone (DTZ) includes the dorsomedial and
AVIAN BASAL GANGLIA 517

FIG. 4. Drawings of cross sections illustrating the comparability of the avian dorsal thalamic zone (DTZ) and the mammalian intralaminar,
mediodorsal, and midline thalamic nuclear complex (IMMC). The left column shows schematic transverse sections through the pigeon DTZ at a
rostral (A) and a caudal level (C), while the right column presents schematic transverse sections through the rat IMMC at a rostral (B) and a caudal
level (D). The three different shading patterns indicate comparable regions of the avian DTZ and the mammalian IMMC, based on connections and
neurotransmitter features discussed in Veenman et al. [147]. Note that Korzeniewska and Gunturkun [70] have suggested that the DLP corresponds
to the mammalian posterior thalamic nucleus. Abbreviations: CL, centrolateral thalamic nucleus; CM, central medial thalamic nucleus; DIP, nucleus
dorsointermedius posterior thalami; DLM, nucleus dorsolateralis anterior thalami, pars medialis; DLP, nucleus dorsolateralis posterior thalami; DMA,
nucleus dorsomedialis anterior thalami; DMP, nucleus dorsomedialis posterior thalami; FRf, fasciculus retroflexus; Hb, habenular nuclei; IMD,
intermediodorsal nucleus; LHb, lateral habenular nucleus; MD, mediodorsal nucleus; MHb, medial habenular nucleus; PC, paracentral thalamic
nucleus; PF, parafascicular thalamic nucleus; PV, nucleus paraventricularis; Re, reuniens thalamic nucleus; Rh, rhomboid thalamic nucleus; SHL,
lateral subhabenular nucleus; SPC, nucleus superficialis parvocellularis.

dorsolateral thalamic nuclei, as well as the dorsointermediate pos-
terior nucleus (DIP), and the DTZ zone seems comparable to the
IMMC of mammals (Fig. 4). The distribution of several neuropep-
tides and transmitters within this thalamic region and topographic
considerations (such as the relationship of DIP to fasciculus ret-
roflexus, which closely resembles that of the parafascicular nu-
cleus to that of fasciculus retroflexus) bolster the interpretation that
the avian DTZ contains a field resembling the mammalian in-
tralaminar thalamic nuclei [147]. The inputs of these neuronal
populations also resemble those of the intralaminar thalamic nuclei
in mammals. For example, the avian DTZ receives input from a
variety of cortical regions [70,147,156], and a variety of subcor-
tical regions that include the spinal cord, the cholinergic pedun-
culopontine and laterodorsal tegmental cell groups, the lateral
cerebellar nucleus, the optic tectum, and the ventral pallidum
[10,68,69,70,80,82,152]. These results support the view that an
intralaminar thalamic input to striatum is an ancestral trait of the
basal ganglia for amniotes.
Additional studies indicate the specific similarity of at least part
of the avian DTZ to the mammalian intralaminar thalamic nuclei.
For example, some portions of the DTZ and IMMC have been
shown to receive pallidal input, namely the DIP and parafascicular
nucleus, respectively [82,147]. In addition, some regions of the
DTZ and IMMC have an excitatory input to the striatum that ends
on the spines of striatal projection neurons and it is known that
these thalamic neurons also utilize neuropeptides, including mem-
bers of the neurotensin family [147]. Because thalamostriatal pro-
jections are well developed in anamniotes, it seems likely that the
stem amniotes possessed an intralaminostriatal projection that they
inherited from amphibians.
Nigral Input
In birds and mammal, the striatum receives a massive input
from tegmental dopaminergic cell groups that include the ventral
tegmental area (the A10 catecholaminergic cell group), the sub-
stantia nigra pars compacta (the A9 catecholaminergic cell group),
and the retrorubral field (the A8 catecholaminergic cell group)
518
[36,41,56,69,94,106,114,154]. The ventral tegmental area also tar-
gets the ventral striatum. Although these tegmental dopaminergic
cell groups have typically been considered as located in the mid-
brain, recent analysis indicates that they are located in a tegmental
field that spans the diencephalon (prerubral, posterior tubercle and
retromammillary regions of what has been termed prosomeres 13
by Puelles and coworkers), the midbrain and the isthmic region
[100,102]. This point has aided in confirming the homology of the
dopaminergic cell groups among amniotes and for aiding in their
identification in anamniotes [132].
The major source of dopaminergic input to the dorsal striatum
is the substantia nigra, pars compacta (SNc). This projection
accounts for the dense dopaminergic innervation observed in the
striatum of amniotes [94,106,114]. Within the striatum of both
birds and mammals, the dopaminergic input typically ends on the
spine necks of striatal projection neurons [17,39,40,59,60,62]. It
has been further shown for birds and mammals, that this input
targets both SP and ENK striatal neurons [59,60,71,72], and in
birds it has been shown that there are no major differences between
SP and ENK neurons in the abundance of this input at the
single neuron level [61]. Consistent with the occurrence of dopa-
minergic input to both major types of striatal projection neurons in
birds and mammals, DARPP32 (a marker of dopaminoceptive
neurons) is present in the vast majority of projection neurons in the
mammalian and avian striatum [37,53,117,128], and both SP and
ENK type projection neurons have been shown to possess
DARPP32 in rats and pigeons [7,117].
The signaling mechanisms employed by striatal neurons in
response to the dopaminergic input appear similar in birds and
mammals. Dopamine acts on striatal neurons via D1-type and
D2-type type dopamine receptors (the two pharmacologically de-
fined dopamine receptor types), which are both present in conspic-
uously high levels in the striatum in birds and mammals [11,13,
35,51,52,119,127,128]. As assessed by autoradiographic methods,
the D1-type and D2-type dopamine receptors in birds show the
same binding characteristics for several subtype specific ligands as
in mammals, suggesting that they are structurally similar to their
counterparts in mammals [28,119]. Molecular biological studies
support the apparent similarity of dopamine receptors in birds and
mammals. For example, molecular biological studies have shown
that a number of different genes code for distinct types of D1-type
and D2-type dopamine receptors in mammals [19,31,32,44,134,
137,138,142,157]. D1-type receptors as defined by pharmacology
and gene structure include what have come to be called the D1 and
the D5 receptors (termed the D1A and D1B receptors in mammals
by some investigators) [89]. By contrast, three different genes have
been found to code for D2 type dopamine receptors in mammals,
and these are called the D2, D3, and D4 receptors (which some
authors have termed the D2A, D2B, and D2C receptors, respec-
tively) [140]. Recently, three distinct D1-like dopamine receptor
genes have been identified in domestic chicken, and characterized
as D1-like by their gene sequences and pharmacology [34]. They
have been termed D1A, D1B, and D1D. The D1A receptor appears
to be the avian equivalent of the mammalian D1 receptor, based on
a close similarity in nucleotide sequence. The avian D1B receptor
appears to possess close pharmacological and sequence similarity
to the mammalian D5 receptor and therefore be the avian equiv-
alent of the mammalian D5. The avian D1D receptor appears to be
similar to both the mammalian D1 and D5 receptors, with a closer
similarity to the D5. Because of the latter feature and because of its
D5-like pharmacology, the avian D1D appears to be a second D5
receptor-equivalent in birds, one that seemingly is absent as such
in mammals.
In situ hybridization histochemistry (ISHH) has been used to
determine which of these D1- and D2-type receptors are found on
REINER
neurons of caudate and putamen in mammals. These ISHH studies
and single-cell RT-PCR studies have shown that while D3, D4,
and D5 are expressed in striatum, the D1 and D2 receptors are the
most common types of D1-type and D2-type receptors in striatum
in mammals [42,43,74,75,140]. The ISHH studies and single-cell
RT-PCR studies together with immunohistochemical studies for
the dopamine receptors indicate that D1 and D2 receptors in the
striatum largely reside postsynaptically on striatal projection neu-
rons, which (as noted) are the major striatal targets of dopaminer-
gic terminals [41,54,79,139]. In mammalian striatum, dopamine
D1 receptors appear to be more abundant on substance P-type
projection neurons, while D2 receptors appear to be more abundant
on enkephalin-type projection neurons [42, 43,74,75,139,140]. By
contrast, the D3 and D4 receptors seem more common on limbic
striatal neurons, while D5 levels are relatively low in both limbic
and somatic striatum [75,77,120].
We recently examined the distribution and cellular localization
of dopamine D1A and D1B receptor mRNAs in the forebrain and
midbrain of the domestic chick, using ISHH with 35(S)-dATP
labeled oligonucleotide probes and both film and emulsion auto-
radiography [136]. These studies showed that D1A receptors are
extremely abundant in the medial and lateral striatum of chick,
while D1B receptors are somewhat abundant in medial and lateral
striatum (Fig. 5). At the cellular level, about 60 75% of neurons
in chick striatum were labeled for D1A receptor mRNA, while
about 20 40% of the neurons in the striatum were labeled for D1B
receptor mRNA. The data suggest that, as in mammals, D1A
receptors primarily mediate the D1-type dopaminergic responses
of somatic striatal neurons in birds to dopaminergic input from the
midbrain.
While our data for chick do not establish which type of striatal
projection neuron possesses D1-type receptors, given that SP
neuron abundance is about 60% [6,8], our findings are at least
consistent with the localization of D1A to the SP striatal pro-
jection neurons. Pharmacological data are further consistent with
this notion [6,108]. Systemic administration of dopamine receptor
agonists in mammals produces pharmacologically specific stereo-
typic behavior, such as licking, biting, or grooming in rodents, and
dopamine receptor antagonist administration (or dopamine deple-
tion or the loss of dopaminergic neurons) yields bradykinesia/
akinesia [1]. Similarly, stimulation of dopamine receptors by sys-
temic injection of agonists such as apomorphine produces
stereotypic pecking and/or vocalization in birds [91]. This effect is
pharmacologically specific to dopamine receptors since it can be
blocked by dopamine receptor antagonists [91]. Conversely, do-
pamine antagonists cause tonic immobility and catalepsy in chicks
and pigeons [126,155], and depletion of the pigeon striatum of
dopamine by the destruction of A9 results in bradykinesia and
akinesia [155]. In mammals and birds, activation of dopamine
receptors by nonspecific agonists such as apomorphine increases
the levels of SP protein and/or mRNA in SP striatal neurons,
while it decreases the levels of ENK protein and/or mRNA in
ENK striatal neurons [ 6,41,108]. Conversely, blockade of do-
pamine receptors with a nonspecific antagonist such as haloperidol
or removal of the dopamine input to the striatum by 6-hydroxy-
dopamine lesions of the tegmental dopaminergic neurons results in
the opposite effects. These findings have been taken to suggest that
dopamine, in general, stimulates SP striatal neurons and inhibits
ENK striatal neurons [41], and in mammals these effects have
been attributed to the prevalence of D1 receptors on SP neurons
and the prevalence of D2 receptors on ENK neurons [41]. Given
that the SP and ENK striatal neurons in birds respond to
dopaminergic manipulations as they do in mammals, it seems
likely that they show a differential cellular localization of D1 and
D2 receptors similar to that in mammals.
AVIAN BASAL GANGLIA 519

FIG. 5. In situ hybridization film autoradiograms showing D1A and D1B receptor mRNA distribution in
coronal sections through the mid-telencephalon of chick. D1A receptor mRNA expression is prominent
in the MSt and LSt, while D1B receptor mRNA is abundant in the HV and the striatum. Scale bar: 1 mm.
Abbreviations: E, ectostriatum: DP, dorsal pallidum; HA, hyperstriatum accessorium; Hp, hippocampus;
HV, hyperstriatum ventrale; LSt, lateral striatum; MSt, medial striatum; N, neostriatum.

AVIAN BASAL GANGLIA ORGANIZATIONOUTPUTS
A Pallido-VA/VL-Motor Cortex Pathway in Birds
In mammals, the internal pallidal segment (GPi) projects to the
ventral anterior and ventral lateral nuclei (VA/VL) of the thalamic
ventral tier, which in turn project to motor-related cortices, pro-
viding a route by which the mammalian basal ganglia may influ-
ence cortical control of movement [1,33]. We recently discovered
that a thalamic center comparable to mammalian VA/VL appears
to be present in the dorsal thalamus of birds, and we have termed
the region containing an apparent VA/VL homologue in birds the
ventrointermediate area (VIA) [86]. We have shown that the dorsal
part of VIA receives pallidal input and projects to the rostral part
of the Wulst, which appears comparable in its location, and in its
inputs and outputs to mammalian primary somatosensory-somato-
motor cortex (Fig. 6) [152]. In addition to the input from the
pallidum, dorsal VIA also receives input from the SNr of birds and
the lateral and medial cerebellar nuclei. By these various traits, the
dorsal part of avian VIA resembles the VA/VL nuclei of the
mammalian ventral tier. As suggested by others, the avian nucleus
dorsalis intermedius ventralis anterior (DIVA), which is dorsally
adjacent to VIA, seems to be comparable to the somatosensory part
of the mammalian ventral tier (the caudal ventroposterolateral
nucleus) on the basis of location and connections [70,151,152].
The organization of pallido-VIA projections, the inputs to VIA
from SNr and the cerebellum, and the projection from VIA to the
rostral Wulst all point to this circuit as the avian homologue of the
mammalian GPi-VA/VL-motor and premotor cortex circuit. Func-
tional data are consistent with our finding that a correspondent of
the mammalian GPi-VA/VL-motor/premotor cortex circuit is
likely to exist in birds. Loss or hypofunction of the SP striato-
GPi neurons in mammals results in akinesia and bradykinesia. This
symptom occurs in humans in late stage Huntingtons disease due
to degeneration of SP neurons of the striatum [1,111], while in
Parkinsons disease these symptoms occur due to the degeneration
of dopaminergic nigral neurons and the consequent loss of their
apparently excitatory input to SP striatal neurons [1]. The basis
of such hypokinesia appears to be the increased inhibition of
VA/VL neurons due to heightened activity of GPi neurons upon
the loss or hypofunction of the SP striato-GPi neurons. In birds,
similar symptoms can be produced by destruction of tegmental
dopaminergic neurons by intranigral or intraperitoneal injection of
either 6-hydroxydopamine or MPTP [48,121]. Such hypokinesia is
likely to have its basis in an abnormality in the activity of striato-
pallido-thalamic circuitry similar to that which occurs in mam-
mals. SP striatopallidal neurons are highly abundant in birds, and
it seems likely that they must have access to motor circuitry for
promoting desired movement. The striato-pallido-VIA-Wulst cir-
cuit appears likely to be one such substrate.
Subthalamic Nucleus and Functional Organization
Finally, we have found that, as in mammals, the SP and
ENK striatal projection neurons in birds are the sources of the
functionally distinct so-called direct and indirect output pathways,
respectively, by which the basal ganglia appear to execute their
role in motor functions (Fig. 6). In mammals, the external pallidal
segment (GPe) projects to the subthalamic nucleus (STN) [1,41,
47], which projects heavily to the GPi and the substantia nigra,
pars reticulata (SNr), with the STN projections utilizing the exci-
tatory amino acid glutamate [1,41,66,67]. Because both the GPi
and the SNr project to the thalamic VA/VL region that projects to
premotor and motor cortex, the pallidal pathway to the STN is in
a position to play an important role in basal ganglia functions [1].
Activation of ENK striato-GPe neurons produces inhibition of
GPe neurons, therefore producing a disinhibition of glutamatergic
neurons of the STN that provide an excitatory input to the GPi and
SNr. The end result of this is that activation of ENK striato-GPe
neurons leads to enhanced inhibition of thalamic ventral tier neu-
rons by GPi and SNr. It is presumed that this circuit promotes
suppression of unwanted movements because the GPi and SNr
neurons whose activity is indirectly enhanced by ENK striatal
neuron activation appear to be those that suppress movements
potentially conflicting with the movements being promoted by the
520 REINER

FIG. 6. Circuit diagram of the functional organization of the basal ganglia in birds. The pluses and minuses indicate
whether specific projections are excitatory () or inhibitory (). The characteristic transmitter used by each major type
of projection neuron is shown. As in mammals, the striatal and pallidal output circuitry of birds appears to be organized
into direct SP striatal outputs to pallidal neurons promoting movement and ENK striatal outputs to pallidal neurons
inhibiting conflicting movement. The pallidal neurons of the indirect pathway have direct outputs to the targets of the SP
striatal neurons (i.e., GPi, SNr, and SpL) and indirect outputs to these same targets via ALa (i.e., the subthalamic nucleus
of birds). In mammals, SP neurons target two populations of pallidal-type neurons (GPi and SNr), while in birds three
are targeted (GPi, SNr, and SpL). It is not yet certain, however, for birds whether ALa projections and GPe-type pallidal
projection neurons (i.e., receiving ENK input) specifically project to GPi type neurons (i.e., receiving SP input) within the
dorsal pallidum. The latter projection has been demonstrated in mammals [115]. Abbreviations: ALa, anterior nucleus of
the ansa lenticularis; ENK, enkephalin; GABA, -aminobutyric acid; GLUT, glutamate; GPe, external segment of globus
pallidus; GPi, internal segment of globus pallidus; SNr, substantia nigra pars reticulata; SP, substance P; SpL, nucleus
spiriformis lateralis; TeO, optic tectum; VIA, ventrointermediate thalamic area.
AVIAN BASAL GANGLIA 521

FIG. 7. Images from transverse sections showing anterogradely labeled fibers in the anterior nucleus of the ansa
lenticularis (ALa) and a few neurons showing light retrograde labeling following a BDA10k injection into the dorsal
pallidum, at a low and high magnification (A,B). The arrows in (A) and (B) indicate the same retrogradely labeled
neuron. Also shown are images from transverse sections showing neuronal perikarya in ALa immunolabeled for
glutamate (C) and retrogradely labeled by BDA3k injection into the dorsal pallidum (D). Note that ALa overlaps the
medial edge of the ansa lenticularis (AL). Medial is to the left and dorsal to the top in all images. Images (C) and (D)
are at the same magnification.

SP striato-GPi circuit [2,111]. Ablation of STN or hypofunction
of the striato-GPe-STN circuit results in hyperkinesia [1,33]. Thus,
concomitant activation of SP striato-GPi/SNr and ENK striato-
GPe neurons (which would presumably occur in a normal basal
ganglia) should promote desired movement and inhibit movements
potentially conflicting with ongoing planned movements.
Critical to our conclusion that the functional organization of the
basal ganglia in birds is also characterized by direct and indirect
striatal motor outputs is our recent identification of the avian
subthalamic nucleus, which in birds has been recognized by the
name the anterior nucleus of the ansa lenticularis (ALa) [57]. As
true of many structures in birds that have now-evident homologues
in mammals (such as the striatum and pallidum), the homology had
been obscured by the cytoarchitectonic dissimilarities between the
mammalian subthalamic nucleus and the avian ALa. Nonetheless,
embryological, hodological, neurochemical, and functional evi-
dence point firmly to the conclusion that the two are homologous.
For example, it has been shown in recent years that the neural
tube in vertebrates becomes parcellated into conserved transverse,
segmental divisions (called neuromeres) as well as into longitudi-
nal divisions (such as the alar and basal plates) during develop-
ment [16,65,103,101,123,124,129,130,141]. The boundaries defin-
ing such regionalization of the brain during development can be
used to more rigorously assess than previously possible if puta-
tively homologous structures share a common developmental his-
tory, and thereby provide evidence for or against such a claim of
homology. In mammals, STN neurons first develop within the
mammillary area [4,5,65], which is located within the basal plate
of the sector that has been termed the fourth prosencephalic
neuromere by Puelles and coworkers [101,123,124]. The STN
neurons appear to subsequently migrate dorsally to their adult
position close to the alar plate basal plate boundary near the
cerebral peduncle. In pigeons and chickens, ALa lies medial to the
fibers of the ansa lenticularis (AL), which contains the output
fibers of the dorsal pallidum, and it appears to originate in the
hypothalamic basal plate near the prospective mammillary body,
and it gradually migrates dorsally to a position near the alar plate
in the same segment. The developmental history and final position
of ALa therefore closely resemble those of the mammalian STN.
The similarities between STN and ALa indicated by these
developmental findings is reinforced by the similarities of their
connections and by the similarities of the neurotransmitters used in
these connections (Figs. 7 and 8). We have found that ALa
receives input from dorsal pallidal neurons that themselves receive
input from ENK striatal neurons. Both the pallidal neurons
projecting to ALa and the ENK neurons projecting to the pal-
lido-ALa neurons appear to be GABAergic, as do the vast majority
if not all pallidal and striatal projection neurons in birds [109,143].
This is also the case for the homologous neurons in mammals,
because the pallidal input to STN arises from GABAergic neurons
522 REINER

FIG. 8. Pallidal neurons projecting to anterior nucleus of the ansa lenticularis (Ala) were retrogradely labeled with BDA and
visualized using a rhodamine-conjugated anti-biotin. In some sections containing rhodamine-labeled pallido-ALa neurons,
enkephalin (ENK) terminals were labeled with fluorescein (A and B pair, C and D pair), while in other sections containing
rhodamine-labeled pallido-ALa neurons, substance P (SP) terminals were labeled with fluorescein (E and F pair). The images
of labeling for ENK or SP with respect to the rhodamine-labeled pallido-ALa perikarya shown were captured using confocal
laser scanning microscopy. The two pairs of images showing BDA-ENK double-labeling (A and B, C and D) show two separate
BDA-labeled pallido-ALa neurons. Note that both of these are surrounded and contacted by ENK terminals. By contrast, the
BDA-labeled pallido-ALa neuron in the SP-labeled tissue was not observed to receive SP terminals (E,F), and none of the SP
striatal terminals in the field contact the BDA-labeled pallidal neuron. The location of the BDA perikarya in (A), (C), and (E)
is shown by asterisks in (B), (D), and (F). The magnification is the same in all images.
AVIAN BASAL GANGLIA
of GPe, which receive their striatal input predominantly from
ENK GABAergic neurons [1,108]. We also have shown that
ALa neurons are glutamatergic and project back to neurons of the
avian dorsal pallidum, which are themselves enriched in specific
AMPA-type glutamate receptor subunits, notably GluR4. In these
respects, the ALa-pallidal projection resembles the projection from
STN to GPi in mammals [1,14,93,96,133]. The avian dorsal pal-
lidum, however, is not organized into segments and pallidal neu-
rons receiving either SP (i.e., GPi-type) or ENK (i.e., GPe-
type) striatal input are intermixed in a single dorsal pallidal field
[81,86,87,115]. Our available data suggest it is likely that ALa
targets within this mixed pallidal field include SP-recipient dorsal
pallidal neurons that project to VIA, i.e., GPi-like neurons [57].
Additionally, we have found that, as true of STN, ALa projects
to the lateral part of substantia nigra, whose neurons are GABAer-
gic and therefore correspond to those of mammalian SNr [143].
These nigral neurons also receive SP striatal input [9] and
possess AMPA-type glutamate receptor subunits, notably GluR4.
In these respects, the lateral nigral (SNr-like) neurons in birds
resemble SNr and GPi neurons in mammals [6,14,87,93,96]. Be-
cause both GPi and SNr of mammals project to VA/VL, both the
SP striato-GPi and the SP striato-SNr pathways are considered
parts of the direct motor output system of the basal ganglia in
mammals [1,3,33]. The avian ALa also projects to a cell group
within the pretectum termed the lateral spiriform nucleus (SpL).
While a mammalian homologue of SpL has not been definitively
identified [23,73,112,115], several lines of evidence indicate that
SpL in birds is the target of an additional direct striatal output and
is thereby similar to mammalian GPi and SNr in connectivity and
likely to be analogous therefore in function [87,112,115]. As true
of the GPi-like cell groups in mammals (i.e., GPi itself and SNr),
SpL neurons are GABAergic, receive input from SP striatal
neurons as well as from dorsal pallidal neurons that receive ENK
striatal input (i.e., GPe-like pallidal neurons), and are notably
enriched in GluR4 [64,82,87,93,112,113,143]. The SpL itself
projects to the tectal layers containing the perikarya and dendrites
of neurons with projections to brainstem motor and premotor areas
[81,87,112,113,115]. Thus, in both birds and mammals the motor
output of the striatum consists of: (1) output circuits arising from
SP striatal neurons having input to GPi-like pallidal-type neu-
rons that exert a direct influence on thalamocortical or tectobulbar
motor circuits; and (2) output circuits arising from ENK striatal
neurons having input to GPe-like pallidal-type neurons that exert
an indirect effect on thalamocortical or tectobulbar motor circuits
via an STN/ALa input to GPi-like neurons of the direct pathways.
Our behavioral studies further support the view that STN and
ALa are homologous [57]. In contrast to the sustained contralateral
hemiballism resulting from large unilateral STN lesions in pri-
mates [1,24], STN lesions in rats produce only transient contralat-
eral hyperkinesia and rotation [58,97]. As in rats, we found that
large unilateral lesions of ALa transiently produce contraversive
hyperkinesia and spontaneous rotation in pigeons. Additionally,
our results indicate that acute apomorphine treatment of birds with
unilateral ALa lesions causes the birds to rotate to the side of the
lesion. Rats with STN lesions also exhibit rotation to the side of the
lesion after acute apomorphine treatment [58,97]. The contralateral
hemiballism in mammals appears to occur because the cortical
motor areas receiving input from the ipsilateral basal ganglia
control contralateral limbs. The spontaneous movement toward the
limb affected by the STN lesion may occur because the ballism on
that side impairs motor output on that side, leaving it less able to
counterbalance the normal movement output of the opposite limb
controlled by the intact basal ganglia. The similar behavioral
effects of STN lesions in rats and ALa lesions in pigeons suggest
a similar functional role of STN and ALa in suppression of
523
unwanted movements and a similar interplay between the direct
and indirect pathways in effecting basal ganglia-mediated influ-
ences on movement [57,87,115].
SUMMARY AND IMPLICATIONS
In living anamniotes, the basal ganglia are generally poorly
developed, and it is likely this was the case in the anamniotes from
which amniotes arose [46,78]. Although there is some variation in
basal ganglia organization among anamniotes, the dopaminergic
input to the striatum tends to be sparse. Additionally, it appears
that the major source of sensory information to the basal ganglia in
anamniotes arises from the thalamus and not from the cortex.
Thus, pallio-striatal connections and thalamo-pallial pathways
were likely to have been absent or meager in stem anamniotes, and
a pallido-thalamo-cortical motor circuit was unlikely to have been
present. These considerations for anamniotes, the findings we
describe here for birds, and findings in reptiles similar to those in
birds [38,115] suggest that the stem amniotes were characterized
by a major advance in the size and cellular abundance of both the
pallium and subpallium over that observed in anamniotes. For
example, it seems likely that the major aspects of the cellular
organization of the basal ganglia, as well as the glutamatergic and
dopaminergic inputs to striatal projection neurons and the related
receptors and signaling mechanisms employed by specific types of
striatal neurons in stem amniotes were already as observed in
living amniotes. Whether the direct-indirect dual striatal output
pathway organization is and was present in anamniotes is yet
uncertain, but clearly such an organization must have been present
in the stem amniotes, since it is characteristic of the avian and
mammalian basal ganglia.
Thus, the cortical and basal ganglia constituents of the telen-
cephalon must have undergone a great increase in neuron number,
size, and complexity during the anamniote-amniote transition. The
changes that occurred included the appearance of prominent mo-
dality-specific sensory thalamocortical pathways, cortical informa-
tion processing and motor planning areas, and major corticostriatal
pathways. Such changes appear to have been part of an increased
involvement of the forebrain in processing sensory information
and in behavioral planning in amniotes. As part of this, the cortex
appears to have become the major source of the information that
the striatum requires for its role in movement control. The increase
in the size of the basal ganglia appears to have been accompanied
by an increase in the number and rostrocaudal extent of dopami-
nergic neurons projecting to the striatum, and by a massive in-
crease in the abundance of the dopaminergic input to the striatum
[132].
What was the significance of the increased complexity of the
basal ganglia in stem amniotes? The shift from a freshwater
semi-aquatic habitat to a fully terrestrial habitat brought with it the
need to deal with a more complex and variable environment, which
required a more complex and adaptable behavioral repertoire of
food procurement and predator avoidance. Increased complexity of
the peripheral visual and auditory apparatus may have helped
promote such changes. Additionally, changes in musculoskeletal
anatomy in the direction of more sophisticated movement and
locomotor capabilities occurred [22,55,122], and may have re-
quired commensurate enhancements in the neural substrate for
movement control. Increased basal ganglia sophistication may
have allowed early amniotes to achieve control over the more
complex movement and behavioral repertoire allowed by the mus-
culoskeletal changes and elaborations in the thalamocortical cir-
cuitry, and by the newly emerged pallial centers subserving per-
ception, learning and motor planning. Such basal ganglia
elaboration may have been necessary to make it possible to suc-
524 REINER

FIG. 9. The close functional linkage of basal ganglia in amniotes with the pallium suggests that the great expansion of the basal ganglia at the
anamniote-amniote transition must also have been accompanied by a parallel expansion of the pallial fields processing sensory information and having
input to the striatum. This figure depicts such a transformation, using a transverse section of frog telencephalon from Northcutt and Kicliter [92] to
depict the amphibian condition (left) and a hypothetical transverse section of the stem amniote telencephalon (created by modifying an image of a
Nissl-stained section through turtle telencephalon, using Adobe Photoshop image editing). The image of the frog telencephalon shows a line drawing
juxtaposed to a high-contrast Nissl-stained section of the same level, with the olfactory bulb projection area shown by the closely spaced dots in the
line drawing. The amphibian ancestors of stem amniotes are assumed to have lacked a true dorsal cortex, but have possessed an extensive laterally
situated olfactory (i.e., lateral) pallium. This anamnioteamniote transition depicted infers from the data for existing amniotes that the basal ganglia
achieved a level of organization similar to that in living amniotes. Further, olfactory pallial organization similar to that in anamniotes must have been
inherited by stem amniotes, and a cytoarchitonically simple dorsal cortex and proto-dorsal ventricular ridge (DVR) receiving sensory thalamic input
are inferred to have emerged [107]. Differing views of the subsequent evolutionary histories of the dorsal cortex and proto-DVR in the sauropsid and
mammalian lineages have been proposed [104,107]. Abbreviations: dp, dorsal pallium; ds, dorsal striatum; lp, lateral pallium; ls, lateral septum; mot,
medial olfactory tract; mp, medial pallium; ms, medial septum; na, nucleus accumbens; vs, ventral striatum.

cessfully promote the desired and inhibit the nondesired move-
ments from among the now richer repertoire of learned and ste-
reotypic behaviors and movements. In this light then, the major
changes in basal ganglia organization occurring during the evolu-
tion of stem amniotes from amphibians may have been one among
the many key events contributing to the success of early amniotes,
and helped to ensure their successful invasion of a fully terrestrial
habitat.
Finally, it seems important to note that the close functional
linkage of basal ganglia in amniotes with the pallium suggests that
the great expansion of the basal ganglia at the anamniote-amniote
transition must also have been accompanied by a parallel expan-
sion of the pallial fields processing sensory information and having
input to the striatum (Fig. 9). The precise form this pallial expan-
sion may have taken is currently the topic of intense interest
[104,107].
ACKNOWLEDGEMENTS
I thank my many various collaborators over the years who have made
the research presented here possible. I also particularly thank Drs. Harvey
Karten, Bill Hodos, Glenn Northcutt, Steve Brauth, Loreta Medina, Luis
Puelles, and Ann Butler for their many stimulating conversations and ideas
about telencephalic evolution. This work was supported by NS-19620
(A.R.), NS-28721 (A.R.), EY-05298 (A.R.), the Neuroscience Center for
Excellence of the University of Tennessee, Memphis (L.M.), and the
Spanish Ministry of Education and Science (L.M.), to all of whom we are
grateful.
REFERENCES
1. Albin, R. L.; Young, A. B.; Penney, J. B. The functional anatomy of
basal ganglia disorders. Trends Neurosci. 12:366 375; 1989.
2. Albin, R. L.; Reiner, A.; Anderson, K. D.; Penney, J. B.; Young,
A. B. Striatal and nigral neuron subpopulations in rigid Huntingtons
disease: Implications for the functional anatomy of chorea and rigid-
ity-akinesia. Ann. Neurol. 27:357365; 1990.
3. Alexander, G. E.; Crutcher, M. D. Functional architecture of basal
ganglia circuits: Neural substrates of parallel processing. Trends
Neurosci. 13:266 271; 1990.
4. Altman, J.; Bayer, S. A. Development of the diencephalon in the rat.
I. Autoradiographic study of the time of origin and settling patterns of
neurons of the hypothalamus. J. Comp. Neurol. 182:945972; 1978.
5. Altman, J.; Bayer, S. A. Development of the diencephalon in the rat.
II. Correlation of the embryonic development of the hypothalamus
with the time of origin of its neurons. J. Comp. Neurol. 182:973994;
1978.
6. Anderson, K. D.; Reiner, A. The extensive co-occurrence of sub-
stance P and dynorphin in striatal projection neurons: An evolution-
arily conserved feature of basal ganglia organization. J. Comp. Neu-
rol. 295:339 369; 1990.
7. Anderson, K. D.; Reiner, A. Immunohistochemical localization of
DARPP-32 in striatal projection neurons and striatal interneurons:
Implications for the localization of D1-like dopamine receptors on
different types of striatal neurons. Brain Res. 568:235243; 1991.
8. Anderson, K. D.; Reiner, A. Striatonigral projection neurons: A
retrograde labeling study of the percentages that contain substance P
or enkephalin. J. Comp. Neurol. 303:658 673; 1991.
AVIAN BASAL GANGLIA
9. Anderson, K. D.; Karle, E. J.; Reiner, A. Ultrastructural single- and
double-label immunohistochemical studies of substance P-containing
terminals and dopaminergic neurons in the substantia nigra in pi-
geons. J. Comp. Neurol. 309:341362; 1991.
10. Arends, J. J. A.; Zeigler, H. P. Organization of the cerebellum in the
pigeon (Columba livia): II. Projections of the cerebellar nuclei.
J. Comp. Neurol. 306:245272; 1991.
11. Ball, G. F.; Casto, J. M.; Balthazart, J. Autoradiographic localization
of D1-like dopamine receptors in the forebrain of male and female
Japanese quail and their relationship with immunoreactive tyrosine
hydroxylase. J. Chem. Neuroanat. 9:121133; 1995.
12. Barnes, J. M.; Henley, J. M. Autoradiographic distribution of gluta-
matergic ligand binding sites in Xenopus brain: Evidence for intra-
cellular [3H]AMPA binding sites. Brain Res. 626:259 264; 1993.
13. Beckstead, R. M. Association of dopamine D1 and D2 receptors with
specific cellular elements in the basal ganglia of the cat: The uneven
topography of dopamine receptors in the striatum is determined by
intrinsic striatal cells, not nigrostriatal axons. Neuroscience 27:851
863; 1988.
14. Bernard, V.; Gardiol, A.; Fachueux, B.; Bloch, B.; Agid, Y.; Hirsch,
E. C. Expression of glutamate receptors in the human and rat basal
ganglia: Effect of the dopaminergic denervation on AMPA receptor
gene expression in the striatopallidal complex in Parkinsons disease
and rat with 6OHDA lesion. J. Comp. Neurol. 368:553568; 1996.
15. Brauth, S. E.; Ferguson, J. L.; Kitt, C. A. Prosencephalic pathways
related to the paleostriatum of the pigeon (Columba livia). Brain Res.
147:205221; 1978.
16. Bergquist, H.; Kallen, B. Notes on the early histogenesis and mor-
phogenesis of the central nervous system in vertebrates. J. Comp.
Neurol. 100:627 659; 1954.
17. Bouyer, J. J.; Park, D. H.; Joh, T. H.; Pickel, V. M. Chemical and
structural analysis of the relation between cortical inputs and tyrosine
hydroxylase-containing terminals in rat neostriatum. Brain Res. 302:
267275; 1984.
18. Bulfone, A.; Puelles, L.; Porteus, M. H.; Frohman, M. A.; Martin,
G. R.; Rubenstein, J. L. R. Spatially restricted expression of Dlx-1,
Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse
forebrain defines potential transverse and longitudinal segmental
boundaries. J. Neurosci. 13:31553172; 1993.
19. Bunzow, J. R.; Van Tol, H. H. M.; Grandy, D. K.; Albert, P.; Salon,
J.; McDonald, C.; Machida, C. A.; Neve, K. A.; Civelli, O. Cloning
and expression of a rat D2 dopamine receptor cDNA. Nature 336:
783787; 1988.
20. Butler, A. B. The evolution of the dorsal thalamus of jawed verte-
brates, including mammals: Cladistic analysis and a new hypothesis.
Brain Res. Rev. 19:29 65; 1994.
21. Butler, A. B. The evolution of the dorsal pallium in the telencephalon
of amniotes: Cladistic analysis and a new hypothesis. Brain Res. Rev.
19:66 101; 1994.
22. Butler, A. B.; Hodos, W. Comparative vertebrate neuroanatomy
Evolution and adaptation. New York: Wiley-Liss; 1996.
23. Caballero-Bleda, M.; Fernandez, B.; Puelles, L. The pretectal com-
plex of the rabbit: Distribution of acetylcholinesterase and reduced
nicotinamide adenine dinucleitide diaphorase activities. Acta Anat.
144:716; 1992.
24. Carpenter, M. B.; Whittier, J. R.; Mettler, F. A. Analysis of choreoid
hyperkinesia in rhesus monkey. Surgical and pharmacological anal-
ysis of hyperkinesia resulting after lesions in the subthalamic nucleus
of Luys. J. Comp. Neurol. 92:293331; 1950.
25. Chen, Q.; Veenman, C. L.; Reiner, A. Cellular expression of iono-
tropic glutamate receptor subunits on specific striatal neuron types
and its implication for striatal vulnerability in glutamate receptor-
mediated excitotoxicity. Neuroscience 73:715731; 1996.
26. Chen, Q.; Reiner, A. Cellular distribution of the NMDA receptor
NR2A/2B subunits in the rat striatum. Brain Res. 743:346 352;
1996.
27. Chen, Q.; Veenman, C. L.; Knopp, K.; Yan, Z.; Medina, L.; Song,
W. J.; Surmeier, D. J.; Reiner, A. Evidence for the preferential
localization of GluR1 subunits of AMPA receptors to the dendritic
spines of medium spiny neurons in rat striatum. Neuroscience 83:
749 761; 1998.
28. Covelli, V.; Memo, M.; Spano, P. F.; Trabucchi, M. Characterization
525
of dopamine receptors in various species of invertebrates and verte-
brates. Neuroscience 6:20772079; 1981.
29. Cowan, R. L.; Wilson, C. J. Spontaneous firing patterns and axonal
projections of single corticostriatal neurons in the rat medial agranu-
lar cortex. J. Neurophysiol. 71:1732; 1994.
30. Csillag, A.; Szekely, A. D.; Stewart, M. G. Synaptic terminals im-
munolabeled against glutamate in the lobus parolfactorius of domes-
tic chicks in relation to afferents from archistriatum. Brain Res.
750:171179; 1997.
31. Dal Toso, R.; Sommer, B.; Ewert, M.; Herb, A.; Pritchett, D. B.;
Bach, A.; Shivers, B. D.; Seeburg, P. H. The dopamine D2 receptor:
Two molecular forms generated by alternative splicing. EMBO J.
8:4025 4034; 1989.
32. Dearry, A.; Gingrich, J. A.; Falardeau, P.; Fremeau, R. T. Jr.; Bates,
M. D.; Caron, M. G. Molecular cloning and expression of the gene
for a human D1 dopamine receptor. Nature 347:7276; 1990.
33. DeLong, M. R. Primate models of movement disorders of basal
ganglia origin. Trends Neurosci. 13:281285; 1990.
34. Demchyshyn, L. L.; Sugamori, K. S.; Lee, F. J. S.; Hamadanizadeh,
S. A.; Niznik, H. B. The dopamine D1D receptor. Cloning and
characterization of three pharmacologically distinct D1-like receptors
from Gallus domesticus. J. Biol. Chem. 270:4005 4012; 1995.
35. Dietl, M. M.; Palacios, J. M. Neurotransmitter receptors in the avian
brain. I. Dopamine receptors. Brain Res. 439:354 359; 1988.
36. Dube, L.; Parent, A. The monoamine-containing neurons in avian
brain: 1. A study of the brain stem of the chicken (Gallus domesticus)
by means of fluorescence and acetylcholinesterase histochemistry.
J. Comp. Neurol. 196:695708; 1981.
37. Durstewitz, D.; Kroner, S.; Hemmings, H. C.; Gunturkun, O. The
dopaminergic innervation of the pigeon telencephalon: Distribution
of DARPP-32 and co-occurrence with glutamate decarboxylase and
tyrosine hydroxylase. Neuroscience 83:763779; 1998.
38. Fowler, M.; Medina, L.; Reiner, A. Immunohistochemical localiza-
tion of NMDA and AMPA type glutamate receptor subunits in the
basal ganglia of red-eared turtles. Brain Behav. Evol. 54:276 289;
1999.
39. Freund, T. F.; Powell, J. F.; Smith, A. D. Tyrosine hydroxylase-
immunoreactive boutons in synaptic contact with identified striatoni-
gral neurons, with particular reference to dendritic spines. Neuro-
science 13:1189 1215; 1984.
40. Gerfen, C. R. Synaptic organization of the striatum. J. Electron
Microscopic Techniques 10:265281; 1988.
41. Gerfen, C. R. The neostriatal mosaic: Multiple levels of compart-
mental organization in the basal ganglia. Ann. Rev. Neurosci. 15:
285320; 1992.
42. Gerfen, C. R.; Engber, T. M.; Mahan, L. C.; Susel, Z.; Chase, T. N.;
Monsma, F. J. Jr.; Sibley, D. R. D1 and D2 dopamine receptor-
regulated gene expression of striatonigral and striatopallidal neurons.
Science 250:1429 1432; 1990.
43. Gerfen, C. R.; Keefe, K. A.; Steiner, H. D1 and D2 dopamine
receptor-mediated gene regulation in the striatum. In: Merchant, K.,
ed. Pharmacological regulation of gene expression in the CNS. Boca
Raton, FL: CRC Press; 1996:324.
44. Grandy, D. K.; Marchionni, M. A.; Makam, H.; Stofko, R. E.; Alfano,
M.; Frothingham, L.; Fischer, J. B.; Burke-Howie, K. J.; Bunzow,
J. R.; Server, A. C.; Civelli, O. Cloning of the cDNA and gene for a
human D2 dopamine receptor. Proc. Natl. Acad. Sci. USA 86:9762
9766; 1989.
45. Goldman-Rakic, P.; Selemon, L. D. Topography of corticostriatal
projections in nonhuman primates and implications for functional
parcellation of the neostriatum. In: Jones, E. G.; Peters, A., eds.
Cerebral cortex, vol. 5. New York: Plenum Press; 1986:447 466.
46. Gonzalez, A.; Smeets, W. J. A. J.; Marn, O. Evidences for shared
features in the organization of the basal ganglia in tetrapods: Studies
in amphibians. Eur. J. Morphol. 37:151154; 1999.
47. Graybiel, A. M. Neurotransmitters and neuromodulators in the basal
ganglia. Trends Neurosci. 13:244 253; 1990.
48. Greenberg, N.; Font, E.; Switzer, R. C. The reptilian striatum revis-
ited: Studies on Anolis lizards. In: Schwerdtfeger, W. K.; Smeets,
W. J. A. J., eds. The forebrain of reptiles. Current concepts of
structure and function. Basel, Switzerland: S. Karger Press; 1988:
162177.
526
49. Groenewegen, H. J.; Berendse, H. W. The specificity of the nonspe-
cific midline and intralaminar thalamic nuclei. Trends Neurosci.
17:5257; 1994.
50. Haber, S. N.; Nauta, W. J. H. Ramifications of the globus pallidus in
the rat as indicated by patterns of immunohistochemistry. Neuro-
science 9:245260; 1983.
51. Harrison, M. B.; Wiley, R. G.; Wooten, G. F. Selective localization
of striatal D1 receptors to striatonigral neurons. Brain Res. 528:317
322; 1990.
52. Harrison, M. B.; Wiley, R. G.; Wooten, G. F. Changes in D2 but not
D1 receptor binding in the striatum following a selective lesion of
striatopallidal neurons. Brain Res. 590:305310; 1992.
53. Hemmings, H. C. Jr.; Nairn, A. C.; Bibb, J. A.; Greengard, P. Signal
transduction in the striatum: DARPP32, a molecular integrator of
multiple signaling pathways. In: Ariano, M. A.; Surmeier, D. J., eds.
Molecular and cellular mechanisms of neostriatal function. Berlin,
Germany: Springer-Verlag; 1995:283297.
54. Hersch, S. M.; Ciliax, B. J.; Gutekunst, C. A.; Rees, H. D.; Heilman,
C. J.; Yung, K. K. L.; Bolam, J. P.; Ince, E.; Yi, H.; Levey, A. I. EM
analysis of D1 and D2 dopamine receptor proteins in the dorsal
striatum and their synaptic relationships with motor corticostriatal
afferents. J. Neurosci. 15:52225237; 1995.
55. Hildebrand, M.; Bramble, D. M.; Liem, K. F.; Wake, D. B. Func-
tional vertebrate morphology. Cambridge, MA: Harvard University
Press; 1985.
56. Hokfelt, T.; Martensson, R.; Bjorklund, A.; Kleinau, S.; Goldstein,
M. Distributional maps of tyrosine hydroxylase-immunoreactive neu-
rons in the rat brain. In: Bjorklund, A.; Hokfelt, T., eds. Handbook of
chemical neuroanatomy, vol. 2. Classical transmitter in the CNS. Part
I. Amsterdam: Elsevier Science Publishers; 1984:277379.
57. Jiao, Y.; Medina, L.; Veenman, C. L.; Toledo, C.; Puelles, L.; Reiner,
A. Identification of the anterior nucleus of the ansa lenticularis in
birds as the homologue of the mammalian subthalamic nucleus.
J. Neurosci. 20:6998 7010; 2000.
58. Kafetzopoulos, E.; Papadopoulos, G. Turning behavior after unilat-
eral lesion of the subthalamic nucleus in the rat. Behav. Brain Res.
8:217223; 1983.
59. Karle, E. J.; Anderson, K. D.; Reiner, A. Ultrastructural double-
labeling demonstrates synaptic contacts between dopaminergic ter-
minals and substance P-containing striatal neurons in pigeons. Brain
Res. 572:303309; 1992.
60. Karle, E. J.; Anderson, K. D.; Reiner, A. Dopaminergic terminals
form synaptic contacts with enkephalinergic striatal neurons in pi-
geons: An electron microscopic study. Brain Res. 646:149 156;
1994.
61. Karle, E. J.; Anderson, K. D.; Reiner, A. Comparison of dopaminer-
gic input to ENK vs. SP striatal neurons at the EM level. Soc.
Neurosci. Abst. 20:783; 1994.
62. Karle, E.; Anderson, K. D.; Medina, L.; Reiner, A. Light and electron
microscopic immunohistochemical study of dopaminergic terminals
in pigeon striatum using antisera against tyrosine hydroxylase and
dopamine. J. Comp. Neurol. 369:109 124; 1996.
63. Karten, H. J. The organization of the avian telencephalon and some
speculations on the phylogeny of the amniote telencephalon. In:
Noback, C.; Petras, J., eds. Comparative and evolutionary aspects of
the vertebrate central nervous system. Ann. N.Y. Acad. Sci. 167:
146 179; 1969.
64. Karten, H. J.; Dubbeldam, J. L. The organization and projections of
the paleostriatal complex in the pigeon (Columba livia). J. Comp.
Neurol. 148:6190; 1973.
65. Keyser, A. The development of the diencephalon of the Chinese
hamster. An investigation of the validity of the criteria of subdivision
of the brain. Acta Anat. (Basel) 83(suppl. 59):1178; 1972.
66. Kita, H.; Kitai, S. T. Efferent projections of the subthalamic nucleus
in the rat: Light and electron microscopic analysis with the PHA-L
method. J. Comp. Neurol. 260:435 452; 1987.
67. Kita, H.; Kitai, S. T. Glutamate decarboxylase immunoreactive neu-
rons in rat neostriatum: Their morphological types and populations.
Brain Res. 447:346 352; 1988.
68. Kitt, C. A.; Brauth, S. E. Telencephalic projections from midbrain
and isthmal cell groups in the pigeon. I. Locus coeruleus and subco-
eruleus. J. Comp. Neurol. 247:69 91; 1986.
REINER
69. Kitt, C. A.; Brauth, S. E. Telencephalic projections from midbrain
and isthmal cell groups in the pigeon. II. The nigral complex.
J. Comp. Neurol. 247:92110; 1986.
70. Korzeniewska, E.; Gunturkun, O. Sensory properties and afferents of
the n. dorsolateralis posterior thalami of the pigeon. J. Comp. Neurol.
292:457 479; 1990.
71. Kubota, Y.; Inagaki, S.; Kito, S. Innervation of substance P neurons
by catecholaminergic terminals in the neostriatum. Brain Res. 375:
163167; 1986.
72. Kubota, Y.; Inagaki, S.; Kito, S.; Takagi, H.; Smith, A. D. Ultra-
structural evidence of dopaminergic input to enkephalinergic neurons
in rat neostriatum. Brain Res. 367:374 378; 1986.
73. Lagares, C.; Caballero-Bleda, M.; Fernandez, B.; Puelles, L. Recip-
rocal connections between the rabbit suprageniculate pretectal nu-
cleus and the superior colliculus: Tracer study with horseradish
peroxidase and fluorogold. Vis. Neurosci. 11:347353; 1994.
74. Le Moine, C.; Bloch, B. Anatomical and cellular analysis of dopa-
mine receptor gene expression in striatal neurons. In: Ariano, M. A.;
Surmeier, D. J., eds. Molecular and cellular mechanisms of neostria-
tal function. Berlin, Germany: Springer-Verlag; 1995:4557.
75. Le Moine, C.; Bloch, B. D1 and D2 dopamine receptor gene expres-
sion in the rat striatum: Sensitive cRNA probes demonstrate promi-
nent segregation of D1 and D2 mRNAs in distinct neuronal popula-
tions of the dorsal and ventral striatum. J. Comp. Neurol. 355:418
426; 1995.
76. Lumsden, A.; Keynes, R. Segmental patterns of neuronal develop-
ment in the chick hindbrain. Nature 337:424 428; 1989.
77. Mansour, A.; Watson, S. J. Jr.. Dopamine receptor expression in the
central nervous system. In: Bloom, F. E.; Kupfer, D. J., eds. Psycho-
pharmacology: The fourth generation of progress. New York: Raven
Press; 1995:207219.
78. Marn, O.; Smeets, W. J. A. J.; Gonzalez, A. Evolution of the basal
ganglia in terapods: A new perspective based on recent studies in
amphibians. Trends Neurosci. 21:487 494; 1998.
79. Meador-Woodruff, J. H.; Mansour, A.; Healy, D. J.; Kuehn, R.;
Zhou, Q. Y.; Bunzow, J. R.; Akil, H.; Civelli, O.; Watson, S. J.
Comparison of distributions of D1 and D2 dopamine receptor mR-
NAs in rat brain. Neuropsychopharmacology 5:231242; 1991.
80. Medina, L.; Reiner, A. Distribution of choline acetyltransferase immu-
noreactivity in the pigeon brain. J. Comp. Neurol. 342:497537; 1994.
81. Medina, L.; Reiner, A. Neurotransmitter organization and connectiv-
ity of the basal ganglia in vertebrates: Implications for the evolution
of the basal ganglia. Brain Behav. Evol. 46:235258; 1995.
82. Medina, L.; Reiner, A. The efferent projections of the dorsal and
ventral pallidal parts of the pigeon basal ganglia, studied with bio-
tinylated dextran amine. Neuroscience 81:773 802; 1997.
83. Medina, L.; Reiner, A. Do birds possess homologues of mammalian
primary visual, somatosensory and motor cortices? Trends Neurosci.
23:112; 2000.
84. Medina, L.; Smeets, W. J. A. J.; Hoogland, P. V.; Puelles, L. Distribution
of choline acetyltransferase immunoreactivity in the brain of the lizard
Gallotia galloti. J. Comp. Neurol. 331:261285; 1993.
85. Medina, L.; Puelles, L.; Smeets, W. J. A. J. Development of cate-
cholamine systems in the brain of the lizard Gallotia galloti. J. Comp.
Neurol. 350:41 62; 1994.
86. Medina, L.; Veenman, C. L.; Reiner, A. Evidence for a possible avian
dorsal thalamic region comparable to the mammalian ventral anterior,
ventral lateral, and oral ventroposterolateral nuclei. J. Comp. Neurol.
384:86 108; 1997.
87. Medina, L.; Jiao, Y.; Reiner, A. The functional anatomy of the basal
ganglia in birds. Eur. J. Morphol. 37:160 165; 1999.
88. Molnar, M.; Casini, G.; Davis, B. M.; Bagnoli, P.; Brecha, N.
Distribution of proenkephalin mRNA in the chicken and pigeon
telencephalon. J. Comp. Neurol. 348:419 432; 1994.
89. Monsma, F. J. Jr.; Mahan, L. C.; McVittie, L. D.; Gerfen, C. R.;
Sibley, D. R. Molecular cloning and expression of a D1 dopamine
receptor linked to adenylyl cyclase activation. Proc. Natl. Acad. Sci.
USA 87:6723 6727; 1990.
90. Nauta, W. J. H.; Karten, H. J. A general profile of the vertebrate
brain, with sidelights on the ancestry of cerebral cortex. In: Schmitt,
F. O., ed. The neurosciences: Second study program. New York: The
Rockefeller University Press; 1970:726.
AVIAN BASAL GANGLIA
91. Nistico, G.; Rotiroti, D.; Stephenson, J. D. Neurotransmitters and
stereotyped behavior in birds. In: Nistico, G.; Bolis, L., eds. Progress
in nonmammalian brain research, vol. 2. Boca Raton, FL: CRC Press;
1983:89 105.
92. Northcutt, R. G.; Kicliter, E. Organization of the amphibian telen-
cephalon. In: Ebbesson, S. O. E., ed. Comparative neurology of the
telencephalon. New York: Plenum; 1980:203255.
93. Paquet, M.; Smith, Y. Differential localization of AMPA glutamate
receptor subunits in the two segments of the globus pallidus and the
substantia nigra reticulata in the squirrel monkey. Eur. J. Neurosci.
8:229 233; 1996.
94. Parent, A. Comparative neurobiology of the basal ganglia. New
York: John Wiley & Sons; 1986.
95. Parent, A.; Olivier, A. Comparative histochemical study of the corpus
striatum. J. Hirnforschung 12:74 81; 1970.
96. Petralia, R. S.; Wenthold, R. J. Light and electron immunocytochem-
ical localization of AMPA-selective glutamate receptors in the rat
brain. J. Comp. Neurol. 318:329 354; 1992.
97. Piallat, B.; Benazzouz, A.; Benabid, A. L. Subthalamic nucleus lesion
in rats prevents dopaminergic nigral neuron degeneration after striatal
6-OHDA injection: Behavioral and immunohistochemical studies.
Eur. J. Neurosci. 8:1408 1414; 1996.
98. Porteus, M. H.; Bulfone, A.; Liu, J. K.; Puelles, L.; Lo, L. C.;
Rubenstein, J. L. R. DLX-2, MASH-1, and MAP-2 expression and
bromodeoxyuridine incorporation define molecularly distinct cell
populations in the embryonic mouse forebrain. J. Neurosci. 14:6370
6383; 1994.
99. Price, M.; Lemaistre, M.; Pischetola, M.; DiLauro, R.; Duboule, D. A
mouse gene related to Distal-less shows a restricted expression in the
developing forebrain. Nature 351:748 751; 1991.
100. Puelles, L.; Medina, L. Development of neurons expressing tyrosine
hydroxylase and dopamine in the chicken brain: A comparative segmen-
tal analysis. In: Smeets, W. J. A. J.; Reiner, A., eds. Phylogeny and
development of catecholamine systems in the CNS of vertebrates. Cam-
bridge, UK: Cambridge University Press; 1994:381 404.
101. Puelles, L.; Rubenstein, J. L. R. Expression patterns of homeobox and
other putative regulatory genes in the embryonic mouse forebrain sug-
gest a neuromeric organization. Trends Neurosci. 16:472 479; 1993.
102. Puelles, L.; Verney, C. Early neuromeric distribution of tyrosine-
hydroxylase immunoreactive neurons in human embryos. J. Comp.
Neurol. 394:283308; 1998.
103. Puelles, L.; Amat, J. A.; Martnez-de-la-Torre, M. Segment-related,
mosaic neurogenetic pattern in the forebrain and mesencephalon of
early chick embryos: I. Topography of AChE-positive neuroblasts up
to stage HH18. J. Comp. Neurol. 266:247268; 1987.
104. Puelles, L.; Kuwana, E.; Puelles, E.; Bulfone, A.; Shimamura, K.;
Keleher, J.; Smiga, S.; Rubinstein, J. L. R. Pallial and subpallial
derivative in the embryonic chick and mouse telencephalon, traced by
the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6 and Tbr-1.
J. Comp. Neurol. 424:409 438; 2000.
105. Reiner, A. A LANT6-like peptide that is distinct from Neuromedin N
is present in striatal and pallidal neurons in the monkey basal ganglia.
Brain Res. 422:186 191; 1987.
106. Reiner, A. Catecholaminergic innervation of the basal ganglia in
mammals. In: Smeets, W. J. A. J.; Reiner, A., eds. Phylogeny and
development of catecholamine systems in the CNS of vertebrates.
Cambridge, UK: Cambridge University Press; 1994:247272.
107. Reiner, A. A hypothesis as to the organization of cerebral cortex in
the common reptile ancestor of modern reptiles and mammals. In:
Bock, G. R.; Cardew, G., eds. Evolutionary developmental biology of
the cerebral cortex. London: Novartis; 2000:83102.
108. Reiner, A.; Anderson, K. D. The patterns of neurotransmitter and
neuropeptide co-occurrence among striatal projection neurons: Con-
clusions based on recent findings. Brain Res. Rev. 15:251265; 1990.
109. Reiner, A.; Anderson, K. D. Co-occurrence of GABA, parvalbumin
and the neurotensin-related hexapeptide LANT6 in pallidal, nigral
and striatal neurons in pigeons and monkeys. Brain Res. 624:317
325; 1993.
110. Reiner, A.; Carraway, R. E. Immunohistochemical and biochemical
studies on Lys8-Asn9-Neurotensin8-13 (LANT6)-related peptides in
the basal ganglia of pigeons, turtles and hamsters. J. Comp. Neurol.
257:453 476; 1987.
527
111. Reiner, A.; Albin, R. L.; Anderson, K. D.; DAmato, C. J.; Penney, J. B.;
Young, A. B. Differential loss of substance P-containing striatopallidal
and enkephalin-containing striatopallidal projections in Huntingtons
Disease. Proc. Natl. Acad. Sci. USA 85:57335737; 1988.
112. Reiner, A.; Brauth, S. E.; Karten, H. J. Evolution of the amniote basal
ganglia. Trends Neurosci. 7:320 325; 1984.
113. Reiner, A.; Brecha, N. C.; Karten, H. J. Basal ganglia pathways to the
tectum: The afferent and efferent connections of the lateral spiriform
nucleus of pigeons. J. Comp. Neurol. 208:16 36; 1982.
114. Reiner, A.; Karle, E. J.; Anderson, K. D.; Medina, L. Catecholamin-
ergic perikarya and fibers in the avian nervous system. In: Smeets,
W. J. A. J.; Reiner, A., eds. Phylogeny and development of catechol-
amine systems in the CNS of vertebrates. Cambridge, UK: Cam-
bridge University Press; 1994:135181.
115. Reiner, A.; Medina, L.; Veenman, C. L. Structural and functional
evolution of the basal ganglia in vertebrates. Brain Res. Rev. 28:235
284; 1998.
116. Reiner, A.; Medina, L.; Haber, S. N. The distribution of dynorphin-
ergic terminals in striatal target regions in comparison to the distri-
bution of substance P-containing and enkephalinergic terminals in
monkeys and humans. Neuroscience 88:775793; 1999.
117. Reiner, A.; Perera, M.; Paullus, R.; Medina, L. Immunohistochemical
localization of DARPP-32 in striatal projection neurons and striatal
interneurons in pigeons. J. Chem. Neuroanat. 16:1733; 1998.
118. Reiner, A.; Stern, E. A.; Wilson, C. J. Morphology and physiology of
intratelencephalicallly projecting corticostriatal neurons in pigeons as
revealed by intracellular recording and cell filling. Soc. Neurosci.
Abst. 24:662; 1998.
119. Richfield, E. K.; Young, A. B.; Penney, J. B. Comparative distribu-
tion of D-1 and D-2 receptors in the basal ganglia of turtles, pigeons,
rats, cats, and monkeys. J. Comp. Neurol. 262:446 463; 1987.
120. Ridray, S.; Griffon, N.; Mignon, V.; Souil, E.; Carboni, S.; Diaz, J.;
Schwartz, J. C.; Sokoloff, P. Coexpression of dopamine D1 and D3
receptors in islands of Calleja and shell of nucleus accumbens of the
rat: Opposite and synergistic functional interactions. Eur. J. Neurosci.
10:1676 1686; 1998.
121. Rieke, G. L. Movement disorders and lesions of pigeon brainstem
analogues of basal ganglia. Physiol. Behav. 26:379 384; 1981.
122. Romer, A. S. The vertebrate body. Philadelphia: W.B. Saunders &
Co.; 1970.
123. Rubenstein, J. L. R.; Martinez, S.; Shimamura, K.; Puelles, L. The
embryonic vertebrate forebrain: The prosomeric model. Science 266:
578 580; 1994.
124. Rubenstein, J. L. R.; Shimamura, K.; Martinez, S.; Puelles, L. Re-
gionalization of the prosencephalic neural plate. Ann. Rev. Neurosci.
21:445 477; 1998.
125. Sakuri, S. Y.; Albin, R. L.; Reiner, A.; Young, A. B. 3H-MK801
binding in pigeon forebrain. Soc. Neurosci. Abst. 16:90; 1990.
126. Sanberg, P. R.; Mark, R. F. The effect of striatal lesions in the chick
on haloperidol-potentiated tonic immobility. Neuropharmacology 22:
253257; 1983.
127. Schnabel, R.; Braun, K. Development of dopamine receptors in the
forebrain of the domestic chick in relation to auditory imprinting. An
autoradiography study. Brain Res. 720:120 130; 1996.
128. Schnabel, R.; Metzger, M.; Jiang, S.; Memmings, H. C.; Greengard,
P.; Braun, K. Localization of dopamine D1 receptors and dopamino-
ceptive neurons in the chick forebrain. J. Comp. Neurol. 388:146
168; 1997.
129. Shimamura, K.; Hartiga, D. J.; Martinez, S.; Puelles, L.; Rubenstein,
J. L. R. Longitudinal organization of the anterior neural plate and
neural tube. Development 121:39233933; 1995.
130. Shimamura, K.; Martinez, S.; Puelles, L.; Rubenstein, J. L. R. Pat-
terns of gene expression in the neural plate and neural tube subdivide
the embryonic forebrain into transverse and longitudinal domains.
Dev. Neurosci. 19:88 96; 1997.
131. Smeets, W. J. A. J. Catecholamine systems in the CNS of reptiles:
Structure and functional correlations. In: Smeets, W. J. A. J.; Reiner,
A., eds. Phylogeny and development of catecholamine systems in the
CNS of vertebrates. Cambridge, UK: Cambridge University Press;
1994:103133.
132. Smeets, W. J. A. J.; Reiner, A. Catecholamines in the CNS of
vertebrates: Current concepts of evolution and functional signifi-
528 REINER

cance. In: Smeets, W. J. A. J.; Reiner, A., eds. Phylogeny and 148. Veenman, C. L.; Wild, J. M.; Reiner, A. Organization of the avian
development of catecholamine systems in the CNS of vertebrates. corticostriatal projection system: A retrograde and anterograde
Cambridge, UK: Cambridge University Press; 1994:463 481. pathway tracing study in pigeons. J. Comp. Neurol. 354:87126;
133. Smith, Y.; Parent, A. Neurons of the subthalamic nucleus in primates 1995.
display glutamate but not GABA immunoreactivity. Brain Res. 453: 149. Wachtler, K. Observations on the evolution of the cholinergic system
353356; 1988. in the telencephalon of vertebrates. Comp. Biochem. Physiol. 72C:
134. Sokoloff, P.; Giros, B.; Martres, M. P.; Bouthenet, M. L.; Schwartz, 357361; 1982.
J. C. Molecular cloning and characterization of a novel dopamine 150. Wild, J. M. Thalamic projections of the paleostriatum and neostria-
receptor (D3) as a target for neuroleptics. Nature 347:146 151; 1990. tum in the pigeon (Columba livia). Neuroscience 20:305327; 1987.
135. Stefani, A.; Chen, Q.; Flores-Hernandez, J.; Jiao, Y.; Reiner, A.; 151. Wild, J. M. The avian somatosensory system: Connections of regions
Surmeier, D. J. Physiological and molecular properties of AMPA/KA of body representation in the forebrain of the pigeon. Brain Res.
receptors expressed by striatal medium spiny neurons. Dev. Neurosci. 412:205223; 1987.
20:242252; 1998. 152. Wild, J. M. Avian somatosensory system: II. Ascending projections
136. Sun, Z.; Reiner, A. Localization of dopamine D1A and D1B receptor of the dorsal column and external cuneate nuclei in the pigeon.
mRNAs in the forebrain and midbrain of the domestic chick. J. Comp. Neurol. 287:118; 1989.
J. Chem. Neuroanat. 19:211224; 2000. 153. Wilson, C. J. Morphology and synaptic connections of crossed cor-
137. Sunahara, R. K.; Niznik, H. B.; Weiner, D. M.; Stormann, T. M.; ticostriatal neurons in the rat. J. Comp. Neurol. 263:567580; 1987.
Brann, M. R.; Kennedy, J. L.; Gelernter, J. E.; Rozmahel, R.; Yang, 154. Wynne, B.; Gunturkun, O. Dopaminergic innervation of the telen-
Y. L.; Israel, Y.; et al. Human dopamine D1 receptor encoded by an cephalon of the pigeon (Columba livia): A study with antibodies
intronless gene on chromosome 5. Nature 347:80 83; 1990. against tyrosine hydroxylase and dopamine. J. Comp. Neurol. 357:
138. Sunahara, R. K.; Guan, H. C.; ODowd, B. F.; Seeman, P.; Laurier, 446 464; 1995.
L. G.; Ng, G.; George, S. R.; Torchia, J.; Van Tol, H. M. M.; Niznik, 155. Yanai, J.; Silverman, W. F.; Shamir, D. An avian model for the
H. B. Cloning of the gene for a human dopamine D5 receptor with reversal of 6-hydroxydopamine induced rotating behavior by neural
higher affinity for dopamine than D1. Nature 350:614 619; 1991. grafting. Neurosci. Lett. 187:153156; 1995.
139. Surmeier, D. J.; Reiner, A.; Levine, M. S.; Ariano, M. A. Are 156. Zeier, H.; Karten, H. J. The archistriatum of the pigeon: Organization
neostriatal dopamine receptors co-localized. Trends Neurosci. 16: of afferent and efferent connections. Brain Res. 31:313332; 1971.
299 305; 1993. 157. Zhou, Q. Y.; Grandy, D. K.; Thambi, L.; Kushner, J. A.; Van Tol,
140. Surmeier, D. J.; Song, W. J.; Yan, Z. Coordinated expression of H. H. M.; Cone, R.; Pribnow, D.; Salon, J.; Bunzow, J. R.; Civelli, O.
dopamine receptors in neostriatal medium spiny neurons. J. Neurosci. Cloning and expression of human and rat D1 dopamine receptors.
16:6579 6591; 1996. Nature 347:76 80; 1990.
141. Vaage, S. The segmentation of the primitive neural tube in chick
embryos (Gallus domesticus). A morphological, histochemical and LIST OF ABBREVIATIONS
autoradiographical investigation. Adv. Anat. Embryol. Cell Biol.
41:1 88; 1969. AChE, acetylcholinesterase
142. Van Tol, H. H. M.; Bunzow, J. R.; Guan, H. C.; Sunahara, R. K.; ALa, anterior nucleus of the ansa lenticularis
Seeman, P.; Niznik, H. B.; Civelli, O. Cloning of the gene for a CHAT, choline acetyltransferase
human dopamine D4 receptor with high affinity for the antipsychotic DIP, dorsointermediate posterior nucleus
clozapine. Nature 350:610 614; 1991. DIVA, nucleus dorsalis intermedius ventralis anterior
143. Veenman, C. L.; Reiner, A. The distribution of GABA-containing DTZ, dorsomedial thalamic zone
neurons and fibers in the forebrain and midbrain of pigeons, with
particular reference to the basal ganglia and its projection targets.
DVR, dorsal ventricular ridge
J. Comp. Neurol. 339:209 250; 1994. ENK, enkephalin
144. Veenman, C. L.; Reiner, A. Ultrastructural morphology of synapses GPe, external pallidal segment
formed by corticostriatal terminals in the avian striatum. Brain Res. GPi, internal pallidal segment
707:112; 1996. IMMC, intralaminar, mediodorsal, midline thalamic nuclear
145. Veenman, C. L.; Chen, Q.; Reiner, A. Glutamate receptor (GluR) complex
subunit localization in pigeon telencephalon. Soc. Neurosci. Abst. ISHH, in situ hybridization histochemistry
20:996; 1994. SNc, substantia nigra, pars compacta
146. Veenman, C. L.; Medina, L.; Chen, Q.; Reiner, A. Ultrastructural SNr, substantia nigra, pars reticulata
localization of GluR1 glutamate receptor subunit in striatal projection
neurons. Soc. Neurosci. Abst. 22:1201; 1996.
SP, substance P
147. Veenman, C. L.; Medina, L.; Reiner, A. Avian homologues of the SpL, lateral spiriform nucleus
mammalian intralaminar, mediodorsal and midline thalamic nuclei: STN, subthalamic nucleus
Immunohistochemical and hodological evidence. Brain Behav. Evol. VA/VL, ventral anterior and ventral lateral nuclei
49:78 98; 1997. VIA, ventrointermediate area

View publication stats