The Nervous System
3 Main Functions
1. gathering of sensory information from external
stimuli
2. synthesizing information
3. responding to stimuli
Components
I. Central Nervous System (CNS)
II. Peripheral Nervous System (PNS)
Central Nervous System (CNS)
A. Parts
1. Brain – main data center
a. Cerebrum
b. Cerebellum
c. Brain stem
a. Cerebrum
• Its nerve centers are responsible for coordinating
sensory and motor systems in the body, and
perform higher mental functions (consciousness,
thought, reason, emotion, and memory)
• Lobes
1. Frontal - controls specialized motor control,
learning, planning, and speech
2. Parietal - controls somatic or voluntary
sensory functions
3. Occipital - controls vision
4. Temporal - controls hearing and some other
speech
b. Cerebellum
• Responsible for perception, fine motor output,
balance, and posture. Its main function is
maintaining coordination throughout the body.
c. Brain stem
• Controls lower-level functioning such as
respiration and digestion
• Parts
a. Midbrain
– regulates motor function and allows
motor and sensory information to pass from
the brain to the rest of the body
b. Pons
– houses the control centers for respiration
and inhibitory functions
– relays information between higher
regions of the brain and the cerebellum,
processes sensory information and helps
coordinate movement.
c. Medulla
– conduit for fibers running between the
spinal cord and higher regions of the brain,
it contains control centers for involuntary
functions such as blood pressure, breathing,
swallowing and vomiting
– Also helps regulate respiration, as well as
cardiovascular and digestive functioning
d. Diencephalon
– consists of three structures:
1. Thalamus – processes and integrates all
sensory information going to the higher regions
of the brain
2. Hypothalamus – critical for homeostasis, the
maintenance of the body's internal environment
(master regulator of endocrine function by its
control over the pituitary gland -
neuroendocrine regulation)
3. Epithalamus
(These structures effectively enclose the third
ventricle)
2. Spinal cord
• connects the brain and the body's main
receptors
• serves as a conduit for signals for motor
output
• connects the brain and brain stem to all of
the major nerves in the body
Anatomic features common to brain and
spinal cord:
• Jelly-like consistency
• Encased in bone (cranium and spinal
column)
• Bathed in a cerebrospinal fluid (CSF), a
colorless fluid produced by choroid plexus in
the brain and provides a special chemical
environment and protection
• Blood-brain barrier, a membrane of
capillaries that maintains special chemical
environment of nervous tissue
B. Coverings
• Bony and fibrous (cranium and vertebrae)
• Meninges (dura matter, arachnoid matter and pia
matter)
• Cerebrospinal fluid (CSF) serving as protection
and circulatory vehicle:
a. Choroid Plexus – generates fluid
(together with the brain capillaries
form the BLOOD-CSF BARRIER
and the BBB)
b. Arachnoid Villi and Perineural
Spaces of the nerves penetrating the
cribriform plate – remove the fluid to
maintain balance
C. Functions
 • Main control center of the body:
- receives sensory information
- organizes and synthesizes data
- gives instructions for motor output to the
rest of the body
- regulates everything from organ function to
high-level thought to purposeful body
movement)
• Contribute to life and behavior of the organism
(in coordination with the PNS)
D. Types of tissue in CNS
• Gray matter – consists of nerve cell bodies,
dendrites, and axons (neurons are arranged in
layers - cortex, or as clusters - nuclei)
• White matter – consists mostly of axons, and
appears white due to myelin sheathing
E. Major levels of CNS function
1. the spinal cord level
2. the lower brain or subcortical level
3. the higher brain or cortical level
1. The Spinal Cord Level
• A conduit for signals from the periphery of the body
to the brain, or in the opposite direction from the brain
back to the body
• The spinal cord is able to perform highly organized
functions even if it is isolated from the brain (neck cord
transection)
• Neuronal circuits in the cord can cause:
(1) walking movements
(2) reflexes that withdraw portions of the body
from painful objects
(3) reflexes that stiffen the legs to support the body
against gravity
(4) reflexes that control local blood vessels,
gastrointestinal movements, or urinary excretion.
• Cord centers can perform functions by simply
following commands from the upper levels of the
nervous system
2. Lower Brain Or Subcortical Level
• Responsible for most of subconscious activities of the
body that are controlled in the lower areas of the brain-
in the medulla, pons, mesencephalon, hypothalamus,
thalamus, cerebellum, and basal ganglia
- subconscious control of arterial pressure and
respiration—medulla and pons
- control of equilibrium -- combined function of
the cerebellum and the reticular substance of
the medulla, pons, and mesencephalon
- feeding reflexes (salivation and licking of the
lips in response to the taste of food) -- by areas
in the medulla, pons, mesencephalon,
amygdala, and hypothalamus
- anger, excitement, sexual response, reaction to
pain and pleasure (still occur even after
destruction of much of the cortex)
3. Higher Brain Or Cortical Level
• The cerebral cortex is essential for most of thought
processes and extremely large memory storehouse, yet
it cannot function by itself
• The cortex never functions alone but always in
association with lower centers of the nervous system
(for precise function or operation by using information
stored). It is the lower brain centers that initiate
wakefulness in the cerebral cortex, thus opening its
bank of memories
Processing of Information: The "Integrative" Function of
The Nervous System
• somatosensory center – receives & distributes sensory
data
• Synthesis/processing of incoming information in
different cortical centers so that appropriate mental and
motor responses can occur
• More than 99% of the sensory information is regarded by
the brain as irrelevant and unimportant (contact with
clothing worn, attention focus only to an occasional object
in one's field of vision, and noise of the surroundings is
usually relegated to the subconscious)
• Only important sensory information excites the mind, and
these are channeled to different integrative and motor
regions to cause desired response
PERIPHERAL NERVOUS SYSTEM  Responsible for the involuntary and automatic control
Components of all musculature, such as muscle tone, balance,
1. Cerebrospinal nervous system posture and locomotion.
- somatic component of the PNS, which includes 12  Subdivisions:
pairs of cranial nerves and 31 pairs of spinal nerves vestibulospinal
- innervates somatic structures of the head and neck, reticulospinal tracts (do not decussate -
limbs and body wall, and mediates somatic sensory and providing ipsilateral innervation
motor functions rubrospinal and tectospinal tracts do decussate,
2. Peripheral autonomic nervous system and therefore provide contralateral innervation
- The visceral component of the peripheral nervous
system (includes the visceral or splanchnic nerves that are AUTONOMIC PERIPHERAL NERVOUS SYSTEM
connected to the CNS through the somatic nerves) A. Sympathetic fibres: Originate from the thoracic
- It innervates the viscera, glands, blood vessels and spinal nerves and the L1 and L2
non-striated muscles, and mediates the visceral functions. --The sympathetic nervous system (in fight, escape
and overcome the conditions - “fight and flight”
Spinal Reflexes - involuntary response that occurs at a B. Parasympathetic nerves: Come from the S2, S3,
subconscious level in response to a sensory stimulus and S4 spinal nerves to supply the pelvic and lower
abdominal viscera
Components of Reflex Pathways: --The parasympathetic nervous system (“rest and
a. Afferent neurons relaying sensory information digest” system and working opposite order to the
from sensory receptors to the CNS sympathetic). It does NOT actually stop the
b. Efferent neurons conveying the motor stimulus sympathetic process in the body but activates the
back to the effector muscle or gland more tranquil functions of the body and help
c. Interneurons are also present between the afferent maintain a healthy, long-term balance.
and efferent neurons, in all but the simplest The remainder come from extensions of the cranial nerves
reflexes. into the thoracic and abdominal cavities
Roles of the interneuron:
 Stimulatory - in withdrawal reflex (stimulate Neurons
muscle to contract for withdrawal action) 1. Sensory neurons - have sensory receptors which
 Inhibitory - in reciprocal innervation recognize external and internal information that is
 To involve the brain - for inhibitory or received by their dendrites
stimulatory control of reflex actions 2. Motor neuron - located in the motor pathway,
A. Monosynaptic - one synapse in the spinal cord. where information can go either through the
- Only in the simplest of reflexes somatic (voluntary) or autonomic (involuntary)
- Faster than the polysynaptic nervous systems.
- - Soma, dendrites, axon, myelin sheath, node of
B. Polysynaptic reflex (two or more synapses): Ranvier

Descending pathways in motor control: Molecular make-up of the cell

A. Pyramidal Tracts *ECF --- sodium, chloride
 Derive their name from the medullary pyramids of the *ICF --- potassium, phosphate
medulla oblongata which the tracts pass through Generally: larger molecules in the outside and smaller
 Responsible for the voluntary control of the molecules in the inside, therefore inside molecules can
musculature of the body and face move to either direction across the membrane
 Subdivisions:
Corticospinal tracts – supplies the musculature of Signal conduction
the body. a. ACTION POTENTIAL
Corticobulbar tracts – supplies the musculature of Relative positivity and negativity of the intracellular fluid
the head and neck. and the extracellular fluid:
B. Extrapyramidal Tracts ICF: Cation - Potassium
 Originate in the brainstem, carrying motor fibres to the ECF: Cation – Sodium
spinal cord --The signal from sensory receptors initiates the action
potential  Change in ionic concentration outside and
inside of the axon
 An action potential is a rapid, all-or-none change (a
stimulus either produces a full-sized action potential or
fails to do so) in the membrane potential followed by a
return to the resting membrane potential.
Basis: Voltage-dependent ion channels in the plasma
membrane (subthreshold stimulus?)
 Propagated AP:
-has the same shape and size along the entire length of
an axon; usually initiated at the proximal (initial)
segment of the axon; basis of the signal-carrying ability
of nerve cells
-The patterns of conducted AP encode the information
conveyed by nerve cells.
*saltatory conduction - due to sudden rush of sodium ions
through the nodes of ranvier (facilitated)
b. RESTING POTENTIAL (without signal or
stimulus)
Synaptic transmission:
a. axon to denrites
b. neuromuscular junction
The AP reaches the motor axonal ends (telodendria) >
motor endplate (20nm, the junctional gap or synaptic cleft)
> depolarization > calcium channel activation > 4 million
molecules of acetylcholine into the cleft (in the presence of
calcium) > binding to the receptors on the motor endplate
> release and binding of acetylcholine molecules bind to a
postsynaptic nicotinic receptor on the muscle > excitatory
postsynaptic end-plate potential > muscle action potential
> muscle contraction > return to precontractile state once
acetylcholine is broken down by acetylcholinesterase
 Four steps in synaptic transmission
a. Synthesis of the neurotransmitters (acetylcholine,
dopamine, GABA, serotonin, etc.)
b. Release of neurotransmitters from the terminal to
the synaptic cleft as soon as the action potential
arrives
c. Recognition of the neurotransmitter by selective
receptors on the postsynaptic cell to be able to
initiate an action potential
d. Inactivation of the neurotransmitter to avoid
continued of the postsynaptic cell and free the
receptor sites (eg. acetylcholinesterase splits
acetylcholine to acetate and choline)
Diffusion of CSF
The arachnoid granulations act as one-way valves
CSF diffuses from its higher pressure in the arachnoid
space into the venous system of the superior sagittal sinus
It has been suggested that the endothelial cells of the
venous sinus create vacuoles of CSF, which move through
the cell and out into the blood.
HISTOLOGY OF THE NERVOUS SYSTEM: CELLS
OF THE NERVOUS SYSTEM
1. PURKINJE CELLS
Purkinje cells are the efferent projection neurons of the
cerebellar cortex which provide its sole neural output
Purkinje cell axons are myelinated, that synapse on
neurons in the deep cerebellar nuclei, all of which are
inhibitory with gamma-aminobutyric acid (GABA) as the
neurotransmitter.
The inhibitory control exerted by the Purkinje cells on deep
cerebellar nuclei neurons can powerfully regulate and
refine their (nuclei) efferent activity to other brain sites
Intrinsic neurons
1. CEREBELLAR GRANULE CELLS
The smallest, most densely packed, and the most numerous
neuron type in the entire brain
The granule cells are the only intrinsic neurons of the
cerebellum to contribute excitatory input to Purkinje cells,
with glutamine as the primary neurotransmitter
The terminal branches of granule cell dendrites receive
mossy fiber input (granule cell axons are small and
unmyelinated)
2. BASKET CELLS
Found in the deeper parts of the molecular layer near the
Purkinje cell bodies.
Basket cells are so named for the characteristic pericellular
basket that their axons form around Purkinje cell bodies on
which they can exert powerful inhibition.
3. STELLATE CELLS
Usually located in the outer two-third of the molecular
layer and synapse only on Purkinje cell dendritic shafts
where they are inhibitory. The inhibitory influence of
stellate cells is less than that of basket cells, in part because
they synapse more distally on Purkinje cells than do the
basket cells.
4. GOLGI CELLS
Large neurons scattered in the superficial part of the
granular layer just below the Purkinje cell bodies.
Their dendrites extend farther in the cerebellar cortex
reaching both the molecular and granular layers.
Golgi cells receive inputs from mossy fibers as part of a
complex synaptic structure called a glomerulus that
includes mossy fiber terminals and granule cell dendrites.
5. GLIAL CELLS
a. ASTROCYTES
Astrocytes are delicate, star-shaped branching glial cell
Regulate the external chemical environment of neurons by
removing excess ions and recycling neurotransmitters
released during synaptic transmission. Support of
endothelial cells which form the blood-brain barrier,
Play a major role in the repair and scarring process of the
brain and spinal cord following mechanical / inflammatory
injuries. Provide a "guidance" for growing neurons / axons Motor control by the CEREBRAL CORTEX
during the development of the brain. A. Motor areas
Astrocytes support and brace the neurons and anchor them 1. Primary motor cortex
to their nutrient supply lines. They also play an important 2. Premotor cortex (lateral and medial)
role in making exchanges between capillaries and neurons. 3. Suplemental or secondary (frontal eye field and
b. MICROGLIA broca’s are)
they are immunologically inactive 4. Premotor cortex - Located anterior to the primary
can be “activated” via various triggers (all caused by brain motor cortex. Receives processed sensory
injury): elevated levels of pro-inflammatory cytokines, information. Helps to plan complex movements
neuro-inflammatory and neuro-degenerative diseases. and sends the plan to the primary motor cortex
Once activated, microglia assume an amoeboid 5. Lateral Premotor Area - For movements made in a
morphology, and display a behavior similar to specific direction (like primary motor area). But,
macrophages that can clear up the neuronal debris. They are especially important in conditional motor tasks
act as antigen-presenting, phagocytic, and cytotoxic cells, 6. Medial premotor cortex - Also mediates the
all three a hallmark of cells of the immune system. They selection of movements. But, is specialized for
are also able to monitor the health of neurons by detecting initiating movements specified by internal (self-
injuries to the neuron. initiated) rather than in response external cues
c. OLIGODENDROCYTES (“trees with only a few 7. Primary motor cortex - Anterior to the central
branches “) sulcus. Made up of pyramidal cells (its axons run
Found predominantly in the white matter (less frequently all the way down the spinal cord to the pyramids in
in the gray matter) the Medulla). it is required for the initiation of
Their processes surround the axons of nerve cells and purposeful movements (lowest threshold for
isolate them from the environment. eliciting a motor response). Responses are
Wrap their process tightly around the fibers producing an organized somatotopically (with spatial
insulating covering called myelin sheath arrangement of motor responses where adjacent
d. EPENDYMAL CELLS muscles are controlled by adjacent areas in the
Ependymal cells line the ventricles of the CNS, forming a cortex)
permeable barrier between (CSF) and underlying cells 8. Secondary motor cortex in humans is called the
Aid in the circulation of CSF through cilial beat. supplementary motor - Frontal eye field. Anterior
to the premotor cortex. Helps control voluntary eye
Neuroglial cell in the PNS movements.
1. SCHWANN CELLS (perform the functions of 9. The Broca’s area - Located only in the left cerebral
oligodendrocytes and microglial cells) hemisphere. Anterior to the premotor cortex (near
Provide myelination to axons in the PNS. Perform the auditory sensation areas). Helps control motor
phagocytotic activity and clear cellular debris that allows movements for speech production. The
for development and regrowth of PNS neurons. Trophic corresponding area on the right side controls the
support for neurons, production of the nerve extracellular emotional overtones to spoken words (helps dictate
matrix how you say/form the words to speech)
Modulation of neuromuscular synaptic activity. B. Cortical areas:
Presentation of antigens to T-lymphocytes. 1. Premotor area (PMA) is located anterior to the
Oligodendrocytes are cells that have fewer processes primary motor cortex, involved in coupling
compared to astrocytes. They line up along the nerve fibers arbitrary cues to motor acts:
in the CNS and wrap their process tightly around the fibers -for preparation for movement
producing the insulating myelin sheath. Schwann cells are -for sensory guidance of movement
similar in function to oligodendrocytes and microglial -for spatial guidance of reaching
cells. -for direct control of some movements with emphasis on
2. SATELLITE CELLS control of proximal and trunk muscles of the body
Similar in function to astrocytes small cells that surround 2. Supplementary motor area (SMA) - located on the
neurons in sensory, sympathetic, and parasympathetic midline surface of the hemisphere anterior to the
ganglia, helping to regulate the external chemical primary motor cortex; Appears to participate more
environment. Highly sensitive to injury and inflammation, in internal guidance or planning of movement
and appear to contribute to pathological states (such as -for internally generated planning of movement
chronic pain). Satellite cells perform a similar function to -for planning of sequences of movement
astrocytes
-for coordination of the two sides of the body such as in bi-
manual coordination
3. Primary motor cortex (MI) - located on medial
surface of the anterior paracentral lobule. Has been
implicated in control of muscle force or length, and
(more recent data) it encodes higher order
parameters, such as movement direction
-Main contributor to generating neural impulses that pass
down to the spinal cord and control the execution of
movement (played by other motor areas in the brain)
Motor control by the CEREBELLUM
The cerebellum DOES NOT initiate movement, rather:
-It contributes to coordination, precision, and accurate
timing of movement, by integrating sensory inputs from
sensory systems of the spinal cord and from other parts of
the brain (Including the cerebral cortex) and by integrating
them for better motor control
-“fine-tuning” motor activity
-Learning of new motor skills and making smooth
movements (theories by Mar, Albus and Ito)
-Non-motor, cognitive functions such as attention and
language, and in regulating fear and pleasure responses
-Four principles of cerebellum function have been
identified important in the fine-tuning of its activities.
1. Feedforward processing: The unidirectional movement
of signals through the system from input to output, with
very little recurrent internal transmission. Thus the
cerebellum (in contrast to the cerebral cortex), cannot
generate self-sustaining patterns of neural activity.
Signals enter the circuit, are processed by each stage in
sequential order, and then leave.
2. Divergence and convergence: The cerebellum receives
as many as 100 millions input but is able to focus down
to modest number of inputs, processes them very
extensively through its rigorously structured internal
network, and sends out the results via a very limited
number of output cells.
3. Modularity: The cerebellar system is divided into
different modules having a similar internal structure,
but with different inputs and outputs. The output of one
module does not appear to significantly influence the
activity of other modules
4. Plasticity: The synapses of different cells of the
cerebellum are susceptible to modification of their
strength, and adjustable to the influence of each fiber.
This arrangement gives tremendous flexibility for fine-
tuning the relationship between the cerebellar inputs
and outputs.
Motor learning: the Marr-Albus Theory
The cerebellum is necessary for motor learning (most
notable being learning to adjust to changes in sensorimotor
relationships). Each cerebellar Purkinje cell (also) gets
input from one single climbing fiber, which is so strong
that a single climbing fiber action potential will reliably
cause a target Purkinje cell to fire a burst of action
potentials (complex potential). The basic concept of the
Marr-Albus theory: That the climbing fiber with strong
input serves as a teaching signal, which induces a long-
lasting change in the strength of synchronously activated
parallel fiber inputs (validity remains controversial).
Schematic overview of the most important cells in the
cerebellum. The output of the cerebellum is generated by
Purkinje cells and goes through the Deep cerebellar nuclei
(DCN), Climbing fibers (CF) are
innervated through the Inferior olive (IO)
Motor control by the BASAL GANGLIA
Nuclei: caudate nucleus, putamen, globus pallidus (pale
globe, GP) - internal and external, substantia nigra (dark
substance) - reticulata and compacta, lenticular nucleus,
nucleus accumbens, neoestriate body, amygdala
a. CAUDATE - Functions closely with nucleus putamen
(to form the Striatum). A brain structure mostly
innervated by neurons of Dopamine
Participates only in the control of voluntary movement
Recent, it also involved in learning processes and
memory
b. PUTAMEN - Largely for motor control of the body
(close to the caudate)
Plays an important role in Operant Conditioning &
(Instrumental conditioning - learning where behavior is
controlled with consequences, behaviors that are
positively reinforced tend to show up more often, while
behaviors that are punished are extinguished)
Relates to development of feelings (could intervene in
the appearance of feelings of love and hate) - in a latest
research
c. GLOBUS PALLIDUS - Responsible for transmitting
the information projected by the nuclei putamen and
caudate (the striatum) to the thalamus. Two portions: a.
internal - GPi b. external -GPe
d. SUBSTANCIA NIGRA or black substance: Presents a
compact part containing black neurons (due to pigment
neuromelanina - darkens with aging) - storage for
dopamine
Parts: Reticulata and Compacta
Functions are complex (learning, orientation, movement
and oculomotion)
Postulated to influence the direct pathway and the indirect
pathway
e. LENTICULAR NUCLEUS
Does not form a nucleus itself, but rather a 5 cm. long
anatomical region of union between the GP and
putamen
Functions include both the activities by the GP and
putamen.
f. NOSTALGIC BODY (Striated core, neostriated body) GP(external) results in LESS inhibition of STN and
Receives the cerebral structure including caudate nucleus increases in its activity
and the nucleus putamen C. The “return” projection from the STN to GP(internal) is
Characteristics are based on the activities carried of excitatory, thus increased activity in the STN results in
caudate purtamen nuclei more excitation of GP(internal)
g. NUCLEUS ACCUMBENS (non-motor) D. The excited GP(internal) will increase its GABAergic
Activities related to emotional processes and the (inhibitory) activity, thus inhibiting the thalamus
elaboration of feelings Inhibited motor thalamus will then fail to excite the cortex
Credited with important pleasure function (laughter or -- “turning down” cortical motor activity
reward experimentation)
Plays a role In the development of emotions (fear, Role of dopamine
aggression, addiction or the placebo effect) 1. Excitatory effect on cells in the striatum that take
h. AMYGDALA or cerebral tonsil (non-motor) part in the Direct Pathway thru their D1 receptors -
Part of the limbic system (a collection of structures - --> increasing its activity
incl. cortex - involved in emotion, memory, and 2. Inhibitory effect on striatal cells that take part in the
behavior) Indirect Pathway thru their D2 receptors -->
Performs vital actions of processing and storage of inhibiting its (inhibitory) activity
emtional reactions. The region of the reward system and is 3. Over all: The effect of Dopaminergic Nigrostriatal
related to addiction and alcoholism. Most recent research Projection is to INCREASE MOTOR ACTIVITY
shows that it is a basic structure for development of Any movement one makes will require that certain motor
emotional learning. Reponsible for modulating memory commands (i.e., raise arm) be executed and opposing
and allows the deelopment of social cognition commands (i.e., lower arm) be suppressed.
The actions of the direct pathway promote the proper
Pathways in the basal ganglia (direct and indirect): Work execution commands and the indirect pathway suppresses
as a “push-pull” system that can finely control the basal commands related to opposing movements
ganglia output. A correct balance is necessary for normal The direct pathway may “turn up” the appropriate
motor function. All basal ganglia output is thought to be movement commands when it is their turn while the
inhibitory and to suppress thalamic activity --> reduced indirect pathway may “turn down” the commands when it
stimulation of the cortex. Selective activation of different is not their turn
elements of these pathways can create a ‘center-surround’
input to the cortex that selects specific motor activities for Organization of flow of information through the motor
expression while inhibiting others system:
a. Serial organization (communication between levels)
Synergy in CNS b. Parallel organization (multiple pathways within each
DIRECT PATHWAY level)
A. The activated cortical projections to the striatum use the -- Objective of parallel organization:
excitatory transmitter glutamate, thus excitatory (excite 1. Prevent severe deficit, especially movement, if
striatal neurons) damage has occured in any part of the system (Damage
B. The excitatory input turns on the striatal cell, increasing to higher levels results in deficits in motor planning,
its inhibitory output using GABA, thus inhibiting cells in initiation, coordination, and so forth, but movement
the GP internal (GPi). will still possible)
C. The cells in GPinternal that project to thalamus are also 2. Improve the ability of undamaged parts of the motor
inhibitory (use GABA), thus inhibit thalamus. The more system to compensate (at least partially) for injuries to
inhibition the GP (internal) receives, the lesser it sends out other parts of the system.
inhibitory signals to the thalamus. This somatotopic mapping mirrors that of the
Since the motor thalamus receives LESS inhibition, its somatosensory cortex. In fact, the somatosensory cortex is
cells will INCREASE their firing, thus EXCITING the just on the other side of the central sulcus. These two areas
cortex are actually adjacent, being connected by the cortical tissue
INDIRECT PATHWAY that follows the contours of the sulcus (the paracentral
A. Cortical fibers excite striatal neurons that project to lobule).
GP(external). Since striatal neurons are GABAergic
(inhibitory), they decrease the activity in GP(external)
B. The GABAergic cells of GP(external), in turn inhibit
the subthalamic nucleus (STN); the decrease in activity in
The motor cortex is a layered structure, with cells of
different overall shape and structure occupying different
layers. Layer 5 of the cortex contains giant pyramidal or
Betz cells. These cells send processes out over three
separate tracts.
A. The corticobulbar tract supplies motor commands to
cranial nerve motor nuclei of the head and neck
B. The ventral corticospinal tract innervates lower motor
neurons of the axial and proximal muscles
C. The lateral corticospinal tract supplies inputs to lower
motor neurons controlling the muscles of the distal
extremities.
--As these muscles control fine movements, this tract is
essential for delicate and precise actions of the fingers and
hands. These three tracts also contain fibers from other
regions of the cerebrum, including the motor association
cortex, the somatosensory cortex, and the sensory
association area.
Areas of the motor cortex
**The primary motor cortex is the source of most of the
corticospinal axons, but its activity is strongly influenced
by the pallidum, striatum, cerebellum and many other
cortical regions, including the somatosensory area of the
cortex. In some ways the activity of the primary motor
cortex is a committee decision, reached by combining
many influences, and enabled by the striatum and
pallidum.
**The secondary motor cortex in humans is called the
supplementary motor area. It is immediately in front of the
lower limb area of the primary motor cortex, and so is
located mostly on the medial surface of the cerebrum.
Many movements are planned and sequenced in the
secondary motor cortex. These libraries manage planning
and sequencing of complex movements. An example is
Broca's region, which contains movement patterns for
making speech sounds and writing. In 90% of people,
Broca's region is in the left frontal lobe, and these people
are almost all right-handed. In left-handed people, the
Broca's area is found in either the right or left frontal lobe.
**The remainder of the frontal lobe is called the prefrontal
cortex; the prefrontal cortex is related to the generation of
abstract thought and complex social behaviors.
--Association Areas - give meaning to sensations. They are
represented by light blue in diagrams. Each primary
sensory area has an association area that it projects to. It is
what draws upon stored memories to give meaning to
sensations such as recognizing the sound of an ambulance
siren or a car horn or recognizing the feeling in your pocket
are your keys or coins.
--Multimodal Association Areas - This is colored
pink/lavender in the diagrams. These are large areas of the
cerebral cortex that receive sensory input from multiple
different sensory modalities and various association areas
and help make associations between various kinds of
sensory info. We have three multimodal association areas:
Posterior, Anterior and Limbic association areas.
--The posterior association area is where visual, auditory
and somatosensory association areas meet. This is what
gives us our spatial awareness of our body. It is the
kinesthetic sense that is very strong in professional dancers
or athletes for example. On the left side we see the spot in
dashes called Wernicke’s area that deals with reading,
naming things. On the right side this area helps us to
understand emotional overtones/undertones of speech (the
multiple ways of saying “I’m fine”).
--The anterior association area includes the prefrontal
cortex. This part of the brain receives information from
posterior association area and helps integrate that info with
past experience with the help of the limbic association area.
It has a lot to do with thinking and making judgements and
it’s where you understand what’s socially acceptable, how
to behave; just anything related to heavy human
conditioning.
--The limbic association area is located on the medial side
of the frontal lobe. This is what helps form memories and
translates that to motor responses and processes emotions
and guides emotional responses. It’s very important for
social interactions and expressions of the personality.
VASCULAR SYSTEM
How the vascular system functions:
• Uses a series of blood vessels
• Function conjunction with the heart, which acts as a pump
• Forms the cardiovascular system (with the heart)
• Provide oxygen and nutrients to every organ and tissue
• Remove waste products
• Blood Vessels:
Layers (3):
A. Tunica intima (innermost layer)
• Single layer of squamous (flat) epithelial cells or the endothelium
• The smooth lining in direct contact with the blood offers little resistance to blood flow
• Regulates blood flow and prevents clotting
• Produces chemicals (such as nitric oxide -a smooth muscle relaxant) that help regulate blood flow within the
vessel
B. Tunica media (middle layer)
• Thickest layer composed of smooth muscle fibres and elastin
• Ativated sympathetic nervous system that can stimulate the smooth muscle fibres to contract --->
vasoconstriction and decreasing blood flow
• Inhibition of the sympathetic nerves will relax the muscle fibres of the tunica media ---> vasodilation and blood
flow increases
C. Tunica adventitia or externa (outer layer)
• Consists mainly of connective tissue fibres that protect the blood vessels and attach them to surrounding tissues
• Larger blood vessels have additional small vessels – vasa vasorum – that supply blood and nutrients to the tunica
externa and tunica media

Arterial system
• Carries the blood from the heart to other parts of the body
• Contains oxygenated (except for pulmonary and umbilical arteries) blood to provide oxygen, nutrients,
hormones and other substances throughout the body
• Vessels: Arteries and arterioles going to the capillaries, where gaseous exchange takes place
• Arteries have thick walls
• Arterioles have the smallest diameter and wall thins out as they near the capillaries
Venous system
• The veins are thin, elastic vessels that act as a reservoir of blood (capacitance vessels)
• They transport low-pressure blood back to the heart
• large lumen; with valves that ensure a one-way flow of blood to the heart
• Return to the heart carrying metabolic waste
• Vessels: Veins and venules (the venous system) from the capillaries
--Largest venules possess a thin tunica externa and a tunica media thin layers of smooth muscle cells. Venules
are tributaries to form vein.
--The largest veins – the superior and inferior venae cavae – have a large tunica externa further thickened by
smooth muscle bands
• The venous system is an irregular network that tends to follow the course of the arteries.
Capillaries
• The smallest bloods vessels, linking arterioles and venules through networks within organs and tissues
• In intimate contact with the tissues, providing nutrients and removing waste products through their thin walls at
a cellular level
• Act as a semipermeable membrane for the diffusion of gases and transfer of nutrients and waste products
• The single layer of flattened endothelial cells facilitate the exchange of substances between capillaries and
tissues
• Smaller substances (gases, metabolic wastes, lactate, glucose) are transferred across through small slits (pores
or fenestrations)
• Larger vital substances (plasma proteins) are not allowed because the slits are smaller than these proteins)
 • Fluid movement between capillaries and tissues
• How do gas exchange and nutrient transfer happen between capillaries and tissues? According to the Starling
principle (named after physiologist Ernest Starling who described it in 1896), fluid movement through the
capillary walls is governed by hydrostatic pressure and oncotic pressure.
• Like any fluid pushed through a confined space, blood in a capillary exerts pressure on the wall of the vessel
because of the pressure exerted upstream by the blood coming from the arteriole. The blood pressure (BP)
generates hydrostatic pressure, which expels fluid from the pores of the capillary into the interstitial
compartment. The size of the pores in the capillary dictates whether particular nutrients are delivered to
particular tissues. Hydrostatic pressure is highest at the arterial end, and lowest at the venous end, of the
capillary.
• The other influencing force is oncotic pressure, which is underpinned by the principle of osmosis; this is the
passive movement of water through a semipermeable membrane from a region of low solute concentration to
one of high solute concentration, with the aim of achieving equilibrium. In blood, plasma proteins – which
cannot easily pass through the capillary walls – exert an osmotic pressure that tends to pull fluid from the
surrounding tissue (which has a higher water concentration) into the capillary (which has a lower water
concentration). This is referred to as oncotic pressure.
• At the arterial end of the capillary, hydrostatic pressure exceeds oncotic pressure, so fluid moves out of the
capillary into the interstitial compartment. At the venous end of the capillary, the two forces are reversed, so
fluid moves back from the tissue into the capillary.

Physiological regulation of BP
• BP, which is crucial to maintain the perfusion of organs, is influenced by: The total volume of blood in the body;
Cardiac output – the amount of blood pumped out by the heart in one minute;

 Peripheral vascular resistance (PVR), resistance to the flow of blood in the arterial system, which is influenced
by factors including vessel length, lumen diameter, and blood viscosity.
- BP can be affected by a change in cardiac output or PVR. An important measure is the mean arterial pressure
(MAP), which is the pressure that propels blood towards tissues with each cardiac cycle and generates
perfusion pressure to the organs.
- There are various short- and long-term physiological mechanisms that regulate BP
1. Baroreceptor response
--The vasomotor center in the medulla oblongata of the brain, which hosts most of the sympathetic neurons of
the nervous system, has a key role in regulating vascular tone. It transmits signals along sympathetic nerve fibres
to vascular smooth muscle, mostly at the level of the arterioles. This results in vasoconstriction or vasodilation,
with corresponding effects on BP and blood flow to the tissues.
--Alterations in BP are detected by mechanical pressure sensors (baroreceptors) found in the arterial wall of the
carotid sinus (the site between the internal and the external carotid arteries) and the aortic arch. If BP suddenly
rises, the walls of these vessels expand, which increases the frequency of nerve impulses sent to the vasomotor
centre. The vasomotor centre is inhibited, causing reflex vasodilation (reduced vascular tone due to less
sympathetic nerve activity) and a decrease in BP.
--Conversely, if BP falls, the decreased stretch on the arterial walls causes a decrease in baroreceptor firing and
culminates in reflex vasoconstriction and an increase in BP. This is the short-term baroreceptor response
regulating BP.
2. Chemoreceptor response
--A similar phenomenon occurs through a chemically induced reflex via chemoreceptors, which are found in
specialized cells in the arteries of the neck (common carotid arteries) and in the aortic arch. These peripheral
chemoreceptors predominantly detect changes in oxygen, carbon dioxide levels and pH (only carotid bodies).
Along with the central chemoreceptors found in the brain they act to control respiration and maintain oxygen
and acid-base status. However, they can also affect the cardiovascular function either directly by controlling the
vasomotor centre in the brain or indirectly via the pulmonary stretch receptors (Klabunde, 2018).
*Activation of the renin-angiotensin-aldosterone system
--The kidneys and adrenal glands play a crucial role in the long-term regulation of BP, in which a hormonal system
known as the renin-angiotensin-aldosterone system (RAAS) is involved. The RAAS activates the sympathetic nervous
system and regulates plasma sodium and BP, and is targeted by many drugs designed to control BP and treat cardiac
conditions, including the angiotensin-converting enzyme (ACE) inhibitor ramipril or the angiotensin II receptor blocker
irbesartan.
--The RAAS begins with the breakdown of angiotensinogen (a plasma protein produced by the liver) by renin (an
enzyme produced by the kidneys). Specialised cells that make up the juxtaglomerular apparatus of the kidney can sense
changes in BP. When it is low, renin is released, triggering a cascade of enzymatic reactions: angiotensinogen produces
an inactive peptide called angiotensin I; ACE (an enzyme produced by the lungs) converts angiotensin I into angiotensin
II, a potent vasoconstrictor, which triggers an increase in BP.
--Angiotensin II can also trigger the adrenal gland to produce aldosterone, a mineralocorticoid hormone that sends
signals via its receptor in the kidneys. This leads to sodium reabsorption and water regulation, increases blood volume
and ultimately increases BP.
--In addition, the hypothalamic-pituitary axis releases antidiuretic hormone, another hormone important for fluid
balance, which stimulates the kidneys to conserve water. In severe conditions such as a haemorrhage, more antidiuretic
hormone is produced. This can cause vasoconstriction and help restore a falling BP
--Autoregulation of local blood flow
--Some organs and tissues are able to automatically adjust their own blood flow by changing the diameter of the
arterioles (Marieb and Hoehn, 2015). Without autoregulation, a decrease in perfusion pressure could lead to cell death,
while a high perfusion pressure could damage delicate blood vessels. For some organs – particularly the kidneys, heart
and brain, this autoregulation of local blood flow is crucial.
--In an organ capable of autoregulation, when the perfusion pressure drops (which would lead to a fall in blood flow)
the organ responds by reducing the vascular resistance via local vasodilation leading to an increase in blood flow. This
response may be mediated through metabolic, myogenic or endothelial mechanisms (Table 4).
--Not all organs or tissues are capable of autoregulation, and in a ‘passive’ vascular bed, a fall in perfusion pressure and
ultimately blood flow is simply not corrected.

Characteristic of the vascular system:

1. All blood vessels are distensible
2. Adapt with increase pressure by dilatation, thus decrease resistance  increased blood flow at least twice as
much flow increase for each increase in pressure
3. Distensible nature of the arteries allows them to accommodate the pulsatile output of the heart and to average
out the pressure pulsations. This provides smooth, continuous flow of blood through the very small blood vessels
of the tissues.
The most distensible by far of all the vessels are the veins. Even slight increases in venous pressure cause the veins
to store 0.5 to 1.0 liter of extra blood. Therefore, the veins provide a reservoir function for storing large quantities
of extra blood that can be called into use whenever required elsewhere in the circulation.

Difference in Distensibility of the Arteries and the Veins.

--Anatomically, the walls of the arteries are far stronger than those of the veins. Consequently, the arteries, on average,
are about eight times less distensible than the veins. That is, a given increase in pressure causes about eight times as
much increase in blood in a vein as in an artery of comparable size.
--In the pulmonary circulation, the pulmonary vein distensibilities are similar to those of the systemic circulation. But,
the pulmonary arteries normally operate under pressures about one sixth of those in the systemic arterial system, and
their distensibilities are correspondingly greater, about six times the distensibility of systemic arteries.
Vascular Compliance (or Vascular Capacitance)
In hemodynamic studies, it usually is much more important to know the total quantity of blood that can be stored in
a given portion of the circulation for each millimeter of mercury pressure rise than to know the distensibilities of
the Vascular distensibility. Increase in volume Increase in pressure Original volume = ¥ 172 Unit IV The Circulation
individual vessels. This value is called the complianceor capacitance of the respective vascular bed; that
is,Compliance and distensibility are quite different.Ahighly distensible vessel that has a slight volume mayhave far
less compliance than a much less distensiblevessel that has a large volume because compliance is equal to
distensibility times volume
The compliance of a systemic vein is about 24 times that of its corresponding artery because it is about 8
times as distensible and it has a volume about 3 times
as great (8 ¥ 3 = 24).
Volume-Pressure Curves of theArterial and Venous Circulations
A convenient method for expressing the relation ofpressure to volume in a vessel or in any portion of thecirculation
is to use the so-called volume-pressurecurve.In the entire systemic venous ystem, the volumenormally ranges from
2000 to 3500 milliliters, and achange of several hundred millimeters in this volumeis required to change the venous
pressure only 3 to5 mm Hg. This mainly explains why as much as onehalf liter of blood can be transfused into a
healthyperson in only a few minutes without greatly altering
function of the circulation.
Effect of Sympathetic Stimulation or Sympathetic Inhibition on
the Volume-Pressure Relations of the Arterial and Venous
Systems.
It is evident that
increase in vascular smooth muscle tone caused by
sympathetic stimulation increases the pressure at each
volume of the arteries or veins, whereas sympathetic
inhibition decreases the pressure at each volume.
Control of the vessels in this manner by the sympathetics
is a valuable means for diminishing the
dimensions of one segment of the circulation, thus
transferring blood to other segments
For instance, an
increase in vascular tone throughout the systemic circulation
often causes large volumes of blood to shift
into the heart, which is one of the principal methods
that the body uses to increase heart pumping.
Sympathetic control of vascular capacitance is also
highly important during hemorrhage. Enhancement of
sympathetic tone, especially to the veins, reduces the
vessel sizes enough that the circulation continues to
operate almost normally even when as much as 25 per
cent of the total blood volume has been lost.
Delayed Compliance
(Stress-Relaxation) of VesselsThe term “delayed compliance” means that a vesselexposed to increased volume at
first exhibits a largeincrease in pressure, but progressive delayed stretchingof smooth muscle in the vessel wall
allows the pressureto return back toward normal over a period of minutesto hours.Even though none of the blood
isremoved after it is injected, the pressure begins todecrease immediately and approaches about 9 mm Hgafter
several minutes. In other words, the volume ofblood injected causes immediate elastic distention of thevein, but
then the smooth muscle fibers of the vein beginto “creep” to longer lengths, and their tensions
correspondinglydecrease. This effect is a characteristic of allsmooth muscle tissue and is called stress-relaxation
Delayed compliance is a valuable mechanism by
which the circulation can accommodate much extra
blood when necessary, such as after too large a transfusion.
Delayed compliance in the reverse direction is one
of the ways in which the circulation automatically
adjusts itself over a period of minutes or hours to diminished
blood volume after serious hemorrhage.
Arterial Pressure Pulsations
With each beat of the heart a new surge of blood fills
the arteries.Were it not for distensibility of the arterial
system, all of this new blood would have to flow
through the peripheral blood vessels almost instantaneously,
only during cardiac systole, and no flow would
occur during diastole. However, normally the compliance
of the arterial tree reduces the pressure pulsations
to almost no pulsations by the time the blood
reaches the capillaries; therefore, tissue blood flow is
mainly continuous with very little pulsation
A typical record of the pressure pulsations at the
root of the aorta is shown in Figure 15–3. In the
healthy young adult, the pressure at the top of each
pulse, called the systolic pressure, is about 120 mm Hg.
At the lowest point of each pulse, called the diastolic
pressure, it is about 80 mm Hg.The difference between
these two pressures, about 40 mm Hg, is called the
pulse pressure.
Two major factors affect the pulse pressure: (1) the
stroke volume output of the heart and (2) the compliance
(total distensibility) of the arterial tree. A third,
less important factor is the character of ejection from
the heart during systole
In general, the greater the stroke volume output, thegreater the amount of blood that must be accommodatedin the
arterial tree with each heartbeat, and,therefore, the greater the pressure rise and fall duringsystole and diastole, thus
causing a greater pulse pressure.Conversely, the less the compliance of the arterialsystem, the greater the rise in
pressure for a givenstroke volume of blood pumped into the arteries. Forinstance, as demonstrated by the middle
top curves inFigure 15–4, the pulse pressure in old age sometimesrises to as much as twice normal, because the
arterieshave become hardened with arteriosclerosis and thereforeare relatively noncompliant.In effect, then, pulse
pressure is determined approximatelyby the ratio of stroke volume output tocompliance of the arterial tree.Any
condition of the circulationthat affects either of these two factors alsoaffects the pulse pressure
Transmission of Pressure Pulses
to the Peripheral Arteries
When the heart ejects blood into the aorta during
systole, at first only the proximal portion of the aorta
becomes distended because the inertia of the blood
prevents sudden blood movement all the way to the
periphery. However, the rising pressure in the proximal
aorta rapidly overcomes this inertia, and the wave
front of distention spreads farther and farther along
the aorta, as shown in Figure 15–5.This is called transmission
of the pressure pulse in the arteries.
The velocity of pressure pulse transmission in thenormal aorta is 3 to 5 m/sec; in the large arterialbranches, 7 to 10
m/sec; and in the small arteries, 15 to35 m/sec. In general, the greater the compliance ofeach vascular segment, the
slower the velocity, which
explains the slow transmission in the aorta and themuch faster transmission in the much less compliantsmall distal
arteries. In the aorta, the velocity of transmissionof the pressure pulse is 15 or more times thevelocity of blood flow
because the pressure pulse issimply a moving wave of pressure that involves littleforward total movement of blood
volume
Damping of the Pressure Pulses in the Smaller Arteries, Arterioles,
and Capillaries
In fact,only when the aortic pulsations are extremely large orthe arterioles are greatly dilated can pulsations
beobserved in the capillaries.This progressive diminution of the pulsations in theperiphery is called damping of the
pressure pulses.Thecause of this is twofold: (1) resistance to blood movementin the vessels and (2) compliance of
the vessels.The resistance damps the pulsations because a smallamount of blood must flow forward at the pulse
wavefront to distend the next segment of the vessel; thegreater the resistance, the more difficult it is for this tooccur.
The compliance damps the pulsations becausethe more compliant a vessel, the greater the quantityof blood required
at the pulse wave front to cause anincrease in pressure. Therefore, in effect, the degree ofdamping is almost directly
proportional to the productof resistance times compliance.
Clinical Methods for MeasuringSystolic and Diastolic Pressures
It is not reasonable to use pressure recorders thatrequire needle insertion into an artery for makingroutine pressure
measurements in human patients,although these are used on occasion when specialstudies are necessary. Instead,
the clinician determinessystolic and diastolic pressures by indirect means,usually by the auscultatory
methodHowever, when the cuff pressureis great enough to close the artery during part of thearterial pressure cycle,
a sound then is heard with each
pulsation. These sounds are called Korotkoff sounds.
The exact cause of Korotkoff sounds is still
debated, but they are believed to be caused mainly
by blood jetting through the partly occluded vessel
Normal Arterial Pressures as Measured by the Auscultatory
Method. Figure 15–8 shows the approximate normal
systolic and diastolic arterial pressures at different
ages. The progressive increase in pressure with age
results from the effects of aging on the blood pressure
control mechanisms.A slight extra increase in systolic pressure usually
occurs beyond the age of 60 years. This results from
hardening of the arteries, which itself is an end-stage
result of atherosclerosis. The final effect is a bounding
systolic pressure with considerable increase in pulse
pressure, as previously explained.
Mean Arterial Pressure. The mean arterial pressure is the
average of the arterial pressures measured millisecondby millisecond over a period of time. It is not equal tothe
average of systolic and diastolic pressure becausethe arterial pressure remains nearer to diastolic pressurethan to
systolic pressure during the greater partof the cardiac cycle.Therefore, the mean arterial pressureis determined about
60 per cent by the diastolicpressure and 40 per cent by the systolic pressure
Veins and Their Functions
For years, the veins were considered to be nothing
more than passageways for flow of blood to the heartEspecially important, they are capable
of constricting and enlarging and thereby storing
either small or large quantities of blood and making
this blood available when it is required by the remainder
of the circulation. The peripheral veins can also
propel blood forward by means of a so-called venous
pump, and they even help to regulate cardiac output,
an exceedingly important function