Neuroanatomy deals with the structure of the nervous system.

All nervous systems consist of

astonishingly similar elements, the nerve cells or neurons. Despite this fact, nervous systems of
different animal classes can be organized in strikingly different ways, and in individual brains
different anatomical structures can be made out that are obviously related to different functions.
In some of these brain parts, one can easily draw conclusions from their particular structure
onto the particular kind of information processing in them.
Contents
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1 Macroscopic neuroanatomy

2 Kinds of nervous systems

3 The neuron

4 Glia cells

5 Microscopic neuroanatomy
o

5.1 Architectonics

5.2 Visualization of individual neurons

5.3 The Neuropil

5.4 Activity stains

5.5 Tracing distant connections

6 Quantitative neuroanatomy

7 Some essential aspects of connectivity

o

7.1 Excitation and inhibition

7.2 Divergence and convergence

7.3 Specificity

7.4 Dendritic spines

7.5 Spatially focused vs. diffuse projections

8 Some examples of connectivity schemes

9 References

10 External links

11 See also

Macroscopic neuroanatomy
There are two major subdivisions in the vertebrate nervous system: the central nervous system,
consisting of the brain and spinal cord, and the peripheral nervous systemwhich connects the
central nervous system via nerves to the sensory receptors and the effectors (muscles, glands).
In humans, 31 pairs of spinal nerves emanate from the spinal cord, providing the extremities
and the trunk with sensory and motor nerve fibers. The head region is provided by 12 pairs of

nerves emanating from the brain. One of them, the vagus nerve, also descends to the trunk and
innervates inner organs, together with fibers coming from the spinal cord. The two most
anterior nerves, the olfactory and the optic tract, carry already pre-processed sensory
information from the olfactory bulb and the eye, respectively, and are considered not as part of
the peripheral nervous system but as a part of the brain (central tracts) itself.
A functional distinction, involving both the central and the peripheral nervous system, can be
made between the so-called somatic and the vegetative or visceral nervous system. The first
deals with the interaction of the animal with the external world, while the vegetative nervous
system is involved in the regulation of the body organs (homeostasis of the internal milieu).
Based on embryological criteria the vertebrate brain has been subdivided into five main regions:
telencephalon, diencephalon, mesencephalon, metencephalon and myelencephalon (Fig. 1).

Figure 2: Two neurons (pyramidal cells) from the cortex of a monkey; Golgi stain. The axon can usually be
distinguished from the dendrites by its smaller diameter and by the conical shape of its initial segment. In
addition, the dendrites of pyramidal cells and of some other types of neurons are densely studded with
dendritic spines. A few axonal ramifications are marked by white arrows.

Kinds of nervous systems

The first nervous systems can be found in Coelenterates where they form loose nets over
extended regions of the body. In the course of evolution an increasing tendency of nerve cells to
conglomerate into lumps of nervous tissue can be found, often clearly associated with special
tasks in the neural computation underlying behavior. The resulting differentiation of a central
nervous system is strikingly different in different groups of animals (e.g. vertebrates,

cephalopods, arthropods). In each group, however, a general scheme can be recognized in every
single species, suggesting common principles in the control of behavior.
Loose nerve nets are also found around the inner organs of vertebrates as part of the vegetative
nervous system.

Figure 3: Neuron (pyramidal cell) from the cortex of a rat, stained by intracellular injection with biocytin; dark
field illumination. Several dendrites, studded with dendritic spines, emanate from the cell body (black) and
ramify in the upper cortical layers. The axon descends into the opposite direction towards the white matter and
ramifies loosely. Synaptic boutons, arranged like pearls on a string, can be recognized along its ramifications.
From: Hellwig B. (2000) A quantitative analysis of the local connectivity betweenpyramidal neurons in layers
2/3 of the rat visual cortex. Biol. Cybern. 82, 111-121,(C)Springer-Verlag Berlin Heidelberg, with kind
permission of Springer Science and Business Media

The neuron
Nerve cells (Figs. 2 and 3) consist of a cell body (soma) and two kinds of cell
processes: dendrites (usually more than one) and one axon (some axonless cells do, however,
exist). Both dendrites and axons may have many ramifications. The dendrites are the recipients
of signals which they convey towards the cell body in the form of a change in the electrical
polarization of the cell membrane. If this change is a depolarization strong enough to reach a
certain electrical threshold at the place where the axon leaves the cell body, a new kind of signal
arises, theaction potential which is propagated along the axon into all its ramifications.

The signal on the axon, unlike that on the dendrites, is conducted with undiminished strength.
The axon can therefore be very long and connect distant parts of the nervous system with each
other or reach distant muscles anywhere in the body. Long axons are often surrounded by
a myelin sheath which consists of several layers of glial cell membrane wrapped around the
axon. This prevents ions from crossing the axonal membrane and, by virtue of a "saltatory"
conduction from one so-called node of Ranvier(short interruption of the myelin sheath) to the
next, makes signal conduction faster than in a naked axon.

Figure 4: Electron microscopic picture of two synapses from the cerebral cortex of the mouse. Membranes of
cellular and subcellular structures are stained with osmium. The arrows point to the dense material that
characterizes the postsynaptic membrane. In A) the postsynaptic element is a dendritic spine (S); in B) it is a
dendrite (D), cut transversally and showing the regular arrangement of microtubuli, as well as two
mitochondria (m). In the axonal part, (Ax) synaptic vesicles can be seen (V). The synapse in A) is excitatory,
recognizable by the thick postsynaptic density (asymmetric or Gray type-I-synapse) and the round vesicles. The
synapse in B) has a thin postsynaptic density (symmetric or Gray type-II-synapse) and more elongated vesicles
- features that characterize inhibitory synapses in the cerebral cortex.

There are a number of interesting differences between neurons in the central nervous system
and sensory neurons of the peripheral nervous system. One example is the neurons which
conduct signals from the skin to the spinal cord. Their cell bodies are located close to the spinal
cord in the so-called spinal ganglia, i.e. far away from the skin. In these neurons, the dendritic
cell process which leads sensory signals in the direction of the cell body has axonal properties: it
is very long, conducts action potentials and can be surrounded by a myelin sheath. The neutral
term nerve fiber refers to both these sensory cell processes and the axons of motor neurons.
The two kinds of processes often run together in the same peripheral nerve.

Different neurons form synapses with each other, structural specializations of the membrane
which can be seen under the electron microscope (Fig.4) and at which the signals are
transmitted from the axon of one neuron, the presynaptic neuron, onto a dendrite or cell body
of another one, the postsynaptic neuron. (More rarely one finds synapses between axon and
axon or dendrite and dendrite). Synaptic transmission usually involves a chemical step.
Thetransmitter substance required is contained in the vesicles visible on the presynaptic side
(Fig.4).
The location of synapses on dendrites and axons can sometimes already be recognized in the
light microscope. In some types of neurons synapses are located on excrescences of the dendritic
membrane (dendritic spines; Fig.2). Also, on axonal ramifications, small swellings (synaptic
boutons) may indicate the presence of synapses (Fig.3). In the central nervous system,
individual neurons often carry many synapses (sometimes tens of thousands), distributed along
their dendrites (input synapses) and axonal ramifications (output synapses). Thus, the
ramification patterns of neurons are powerful indicators of connectivity patterns. They show
where a neuron can receive signals and to where it can distribute them. No synapses are found
where an axon is myelinated.

Figure 5: Cell bodies of some neurons (N), nucleus of an astroglia cell (A) and nuclei of some oligodendroglia
cells (O). Nissl stain of the human cerebral cortex. The cell bodies of nerve cells consist of a large, round, light
nucleus surrounded by cytoplasm. Furthermore, the nucleus contains a well discernible, darkly stained
nucleolus. In glia cells, the cytoplasm is not stained, and the nucleus is smaller and relatively dark, particularly
in oligodendrocytes.

Glia cells
Nervous tissue also contains various kinds of Glia cells. These also consist of a cell body from
which cell processes emanate, but they are usually much smaller than neurons (Fig. 5). Glia cells
are loosely interspersed between the nerve cells and perform supportive functions. In the central
nervous system, the main types are Astroglia, Oligodendroglia and Microglia. The processes
of Astrogliacells fill interstices between nerve cell processes and surround blood vessels. They
contribute to the formation of the blood-brain barrier, supply nerve cells with nutritive
substances and are involved in keeping up the ionic balance in the tissue. Microglia is involved
in the repair of tissue damage and seems to be rare in healthy tissue. In the central nervous

system, oligodendroglia forms the myelin sheath around axons. In the peripheral nervous
system, the myelin sheath is part of so-called Schwann-cells.

Microscopic neuroanatomy

Figure 6: Nissl stain of the visual cortex of the mouse. Layers I to VI can be delineated on the basis of
differences in cell density and cell size. WM: white matter.
From: Braitenberg and Schz (1998), Cortex: Statistics and Geometry of Neuronal Connectivity, (C)SpringerVerlag Berlin Heidelberg, with kind permission of Springer Science and Business Media.

Architectonics
Within the central nervous system of vertebrates, one can even distinguish regions of different
shading with the naked eye on unstained cuts through the brain. The so-called grey
matter contains the cell bodies, dendrites and axonal ramifications of neurons and the synapses
between them. It is the place where neurons interact. The white matter is a cable system,
mediating the interactions between various parts of the grey matter. It contains axons, but no
other neuronal structures. Many of these axons are myelinated, the fatty myelin being
responsible for the light color of the white matter, in contrast to the grey matter which is much
poorer in myelin.
With the aid of histological staining methods a more detailed classification of brain structures
can be made.
The cytoarchitectonic parcellation of the brain is based on the staining of cell bodies with the
aid of basic dyes (Nissl-stain; Fig.6). These stains show local variations in the density and size of
cell bodies, thus enabling the delineation of layers or groups of cells, so-called nuclei, in the
various parts of the brain.

Similar maps, largely coincident with the cytoarchitectonic ones can be delineated on
preparations stained for myelin (myeloarchitectonics). They show regions of white matter and
fiber tracts (see Figure 3 in the article Brain), well distinguished by the arrangement, density
and orientation of myelinated axons. Myelin stains also show interesting patterns of myelinated
fibers within the grey matter, such as in the different areas of the cerebral cortex.

Figure 7: Staining of blood vessels in thehypothalamus of the mouse; Golgi stain. The paraventricular nucleus
(center of the picture) stands out by a particularly dense vascularization.

Another method which reveals some striking local differences of architectonics is the staining of
blood vessels (angioarchitectonics). The main difference is found between grey and white
matter, the grey matter being more richly vascularized. A few particularly densely vascularized
nuclei can be found in the hypothalamus (Fig. 7).
In addition to these traditional histological methods, a variety of histochemical and immunohistochemical techniques are available today, showing the distribution of particular molecules in
the brain (chemoarchitectonics). This enables us to investigate the distribution of subtypes of
neurons or of particular transmitter substances or of postsynaptic receptor molecules under the
microscope (e.g. Amunts et al. 2002). With these methods, we are therefore coming closer to an
understanding of the functional mechanisms in different regions of the brain.
A method which is particularly useful for the delineation of cortical areas in the adult human
brain is the so-calledpigmentoarchitectonics, based on the staining of lipofuscin granules which
accumulate in the soma of nerve cells with age (Braak, 1980).

Visualization of individual neurons

Individual neurons with all their cell processes can be isolated from the tissue by the so-called
Golgi-method (Fig. 2). With this method, only a small number of neurons are stained, the
selection of which seems to be largely random. In the hands of Santiago Ramn y Cajal (1911)
and of others, this method has provided us with most of the basic knowledge on connectivity
patterns. Later, it became possible to fill individual neurons by intracellular injection of dyes

(Fig. 3). This procedure enables us, at the highest level of detail, to visualize neurons, the
physiological properties of which had been investigated beforehand.

Figure 8: Electron micrograph of the cortex of the mouse, showing the density of cell processes in the neuropil.
Membranes of cellular and subcellular structures are stained with osmium. N nucleus of a nerve cell; - C cytoplasm surrounding the nucleus. Most of the other structures are pieces of axons and dendrites and a few
are glia cell processes, some of which are marked by G. D dendritic pieces which receive a synapse on this
section, S spine heads which receive a synapse on this section. A indicates a group of cross sections of very thin
axons.

The Neuropil
The cell processes of the neurons form a dense felt, the so-called neuropil, which fills the space
between the cell bodies and the blood vessels. In the mouse, the neuropil occupies about 84% of
the cortical grey matter (Schz and Palm, 1989). In the electron microscope one can distinguish
the various components: axons, dendrites, dendritic spines, as well as some glia cell processes.
Together, they form a compact mass (Fig. 8) leaving very little extracellular space between the
individual elements and allowing for a high density of synapses of about 7 x 10 8/mm3.

Figure 9: Deoxyglucose stain of a rat brain; coronal section, color coded autoradiography. One whisker was
stimulated for 45 min. before the animal was sacrificed. The high accumulation of deoxyglucose (white spot) in
the right hemisphere reveals the representation of this whisker in the primary somatosensory cortex.

Activity stains
Regions in the brain which have been particularly active during life time can be shown postmortem with the so-called cytochrome oxidase stain. Regions which have been particularly
active during the last hour before the death of the animal can be visualized with
thedeoxyglucose method (Fig. 9). Similar (though not identical) results can be achieved by
staining of the protein c-Fos, an immediate early gene product (e.g. Sadananda and Bischof,
2006; Staiger, 2006).

Tracing distant connections

Various methods exist for tracing distant connections in the brain. In the early years of
neurohistology these connections were mainly investigated on autopsy material of brains in
which localized lesions (due to a stroke or other brain injuries) led to a degeneration of injured
fibers. The degenerated pathways could be followed in histological preparations. Nowadays, socalled tracer substances are used which after injection into the brain of an anesthetized animal
- are taken up by the neurons and transported along the axons. Anterograde tracers are taken
up by the cell bodies at the injection site and transported towards the terminal fields of their
axons; they answer the question: where do the neurons at the injection site project to (Fig.
10)? Retrograde tracers are taken up by the axon terminals and transported towards the cell
bodies. They answer the question: where are the neurons located whose axons reach the
injection site (Fig.11)?

Figure 10: Coronal section through the mouse brain, showing anterograde staining with the tracer biotinylated
dextran amine (BDA). The injection site is located in the cerebral cortex (thick arrow). Axonal projections
emanate from the injection site within the grey matter, and distant projections to the cortex of both
hemispheres (long grey arrows) can be seen, as well as to the thalamus (white arrow). From: Schz A.,
Chaimow D., Liewald D. and M. Dortenmann Quantitative aspects of corticocortical connections: a tracer study
in the mouse. Cerebral cortex 2006, 16 (10), 1474-1486, by kind permission of Oxford University Press.

Figure 11: Retrograde staining of cell bodies of cortico-spinal neurons (band of black cell bodies in layer V) after
injection of the tracer horseradish peroxidase into the spinal cord. Coronal section through a rat brain, showing
the motor cortex of one cortical hemisphere. CC corpus callosum.
From Braitenberg and Schz (1998), Cortex: Statistics and Geometry of Neuronal Connectivity,(C)SpringerVerlag Berlin Heidelberg, with kind permission of Springer Science and Business Media.

With the aid of these methods, many of the connections between the various parts of the brain
have been revealed, as well as many of the connections between the various areas of the cerebral
cortex (e.g. Young et al., 1995).
For more details on tracing and other neuroanatomical methods, see for example Zborsky et al.
(2006) and the previous volumes (Heimer and RoBards, 1981; Heimer and Zborsky, 1989).

Quantitative neuroanatomy
Since one of the scopes of neuroanatomy is to provide a reasonable basis for functional models,
a quantitative assessment of the tissue elements is of importance. One of the difficulties in
measuring and counting structures under the microscope is related to the fact that the
histological sections are often thinner than the structures under investigation. For example,
electron microscopic sections have a thickness of about 60 nm, while synapses (i.e. their discshaped membrane specializations) have diameters of around 350 nm. Light microscopic
sections have thicknesses of 100 m and below, while dendritic trees and terminal axonal arbors
can ramify over several hundred micrometer.
Quantification of neuronal elements therefore makes assumptions about the extension of
structures in the third dimension necessary and/or sophisticated methods of correlation of
neighboring sections. The mathematical-geometrical techniques involved in this (see for
example Russ and Dehoff, 2000) go by the name of stereology.
In the mouse cortex, the density of neurons is about 9 x 10 4/mm3 and the number of synapses
per cortical neuron is about 8000. The total length of dendrite in one mm 3 of cortex is several
hundred meters, while the total length of axon in one mm3 of cortical grey matter is several
kilometers (Braitenberg and Schz, 1998).

Some essential aspects of connectivity

Excitation and inhibition

There are two kinds of neurons: excitatory neurons, the kind where a signal in the presynaptic
neuron activates the postsynaptic neurons, and inhibitory neurons, in which a signal in the
presynaptic neuron diminishes or suppresses the activity of the postsynaptic neurons. By the
combination of electrophysiological, histochemical and neuroanatomical methods, much
knowledge has accumulated on the anatomical appearance of excitatory and inhibitory neurons
and of the two kinds of synapses (Fig. 4). In many parts of the brain it is therefore now possible
to investigate the distribution of these two populations under the microscope.
Individual neurons receive usually both excitatory and inhibitory synapses. These may have a
characteristic distribution on the receiving neuron: in the cerebral and thecerebellar cortex, as
well as the striatum, excitatory synapses are mainly located on dendritic spines, while inhibitory
synapses are mainly located on dendritic shafts and cell bodies.
On the presynaptic side, all the synapses of an individual neuron carry the same transmitter
substance (in some neurons, it is a mixture of several substances) and are either excitatory or
inhibitory. For an overview of the distribution of GABA (gamma-amino butyric acid), the main
inhibitory transmitter in most parts of the brain, see the atlas by Mugnaini and Oertel (1985).

Divergence and convergence

Neurons make usually more than one synapse and many of them make and receive hundreds or
thousands of synapses. In some cases, an axon makes all of its synapses onto one or a few
postsynaptic neurons (e.g. climbing fibers onto Purkinje cells in the cerebellum). In other cases,
an axon may distribute its synapses onto thousands of different neurons (e.g. pyramidal cells in
the cerebral cortex). Dendritic trees can differ in the degree of convergence of the signals that
they receive: all or many of the synapses on a dendritic tree can come from different neurons, or
from only a few. The patterns of ramification may be taken as indicators of the degree of
divergence and convergence between neurons (see also article Brain).

Specificity
Connectivity schemes can differ in the degree to which they are predetermined. Exactly
predetermined connectivity between individual neurons can be found in invertebrate nervous
systems, such as for example the connectivity between the visual receptors in the compound eye
of flies and the first visual ganglion. In large pieces of grey matter, the connectivity is
predetermined on a coarser level, such as by a specificity between neuronal types
(e.g. chandelier cells in the cerebral cortex), or simply by the statistics of the elements in the
neuropil, given by the number and arrangement of neurons of different types and their
ramification patterns. Such a coarsely predetermined connectivity may then be later refined by
learning.

Dendritic spines
It is still unclear why some postsynaptic structures are located on dendritic spines while others
on the same neuron are located directly on the dendrites. There is evidence, however, that
the spine synapses in particular are involved in the refinement of connectivity by learning. One
indication is the fact that synaptic plasticity has been shown for neurons which are densely

studded with spines (pyramidal cells in the cerebral cortex, Purkinje cells in the cerebellum,
medium spiny cells in the striatum).

Spatially focused vs. diffuse projections

Neurons can make relatively circumscribed projections to one or a few other points in the brain,
or they can make wide axonal ramifications that extend over large regions of the brain. These
two patterns go along with an important functional distinction: focused projections are a feature
of neurons involved in the information processing proper, while highly diffuse connections are a
feature of neural systems which provide the background on which information processing is
carried out, related, for instance toemotions or attention. These systems are characterized by
particular transmitter substances (e.g. dopamine, noradrenalin, serotonin, acetylcholine), and
their cell bodies are mainly located in small nuclei in the brain stem or at the basis of the
telencephalon (substantia nigra, locus coeruleus, raphe nuclei, nucleus basalis of Meynert,
respectively). For an anatomical survey see for example Nieuwenhuys (1985) and Fallon and
Laughlin (1987).

Figure 12: Highly abstract schemes of some basic types of connectivity in the mammalian brain. For each of the
four parts of the brain, only the quantitatively dominant and/or most characteristic type of neuron is shown. In
A) pyramidal cells are connected with each other both within the grey matter and via the white matter, forming
a large excitatory network, with only few inhibitory neurons interspersed (not shown here); in B) medium spiny
stellate cells form an inhibitory network among themselves; in C) granule cells (circles) do not form synapses
with each other, but relay their excitation only onto Purkinje cells (triangles) and other inhibitory neurons; in
D) the (excitatory) thalamic relay neurons seem not to form synapses with each other, but only with inhibitory
thalamic interneurons (not shown here). The external arrows indicate the sign of the inputs and outputs. All
four parts of the brain receive excitatory inputs. The outputs are also excitatory in case of the cerebral cortex
and the thalamus. The basal ganglia and the cerebellar cortex have inhibitory outputs, arising from the medium

spiny neurons in B) and from the Purkinje cells in C). Modified from: Schz A. (2001) What can the cerebral
cortex do better than other parts of the brain? In: Brain, Evolution and Cognition. (C) Wiley and Sons, New
York, and Spektrum Akademischer Verlag, Heidelberg, pp. 491-500, with kind permission.

Some examples of connectivity schemes

How parts of the brain can differ in their internal connectivity is sketched in Fig.12 for the four
largest parts of the brain. (These sketches show only the quantitatively dominant and/or the
most characteristic type of neurons).
The neurons in the cerebral cortex (Fig.12 a) form a rich network among themselves. The
number of synapses coming from input fibers are only a small percentage of all synapses in the
cortex. The neurons in the striatum (Fig. 12 b) also form a network among themselves. However,
one fundamental difference between these two parts of the brain is the fact that most of the
neurons in the cerebral cortex, the pyramidal cells, are excitatory, while most of the neurons in
the striatum are inhibitory.
In both the thalamus (Fig.12 d) and the cerebellar cortex (Fig.12 c), just as in the cerebral cortex,
most of the neurons are excitatory. However, in contrast to the cerebral cortex, the excitatory
neurons of the cerebellar cortex do not form a network among themselves, and the same seems
to be true for the relay neurons in the thalamus (Steriade et al., 1990). The excitatory neurons of
the thalamus relay their activity mainly directly to their target structure, the cerebral cortex, and
to a certain extent also to inhibitory neurons within the thalamus, while those in the cerebellar
cortex (the granule cells) project exclusively onto the various kinds of inhibitory neurons within
the cerebellar cortex. Another outstanding feature of the cerebellar cortex is the particular
geometry of its neurons which leads to a one-dimensional spread of excitation in latero-lateral
direction only.
For more detailed information on the connectivity of these brain structures and for a functional
interpretation see for example Steriade et al. (1990), Braitenberg et al. (1997), Braitenberg and
Schz (1998), Miller (2007).

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