Chp 6

Neuronal Signaling and the Structure

of the Nervous System

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 The Nervous System

• The Nervous System has two major divisions:

– The Central Nervous System (CNS), which is
composed of the brain and spinal cord.
– The Peripheral Nervous System (PNS) is composed
of the nerves that connect the brain or spinal cord
with the body’s muscles, glands, and sense organs.
• The neuron is the basic cell type of both systems.

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 Neurons
• These are the “nerve cells”.
• They are amitotic, so they
do not divide. They also
have a very high metabolic
rate.
• Clusters of cell bodies in
the CNS are called nuclei.
• Neurons are not the most
numerous cell in the CNS;
Glial cells are.

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Glial Cells

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 Glial Cells of the CNS
• The glial cells of the CNS are:

• Astrocytes: support cells, control extracellular

environment of neurons
• Microglia: “immune system” of the CNS
• Ependymal cells: ciliated, involved with production
of CSF and CSF movement
• Oligodendrocytes: responsible for the myelin

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Glial Cells of the PNS
• Schwann cells surround
and form myelin sheaths
around the larger nerve
fibers. These are vital to
regeneration and proper
nerve signal conduction.

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Axonal Transport Maintains Axon
Structure & Function

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Functional Classes of Neurons

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9
Development of the Nervous System
• Development of the nervous system in the embryo begins
with stem cells that can develop into neurons or glial cells.
• After the last cell division, each neuronal daughter cell
differentiates, migrates to its final location, and sends out
processes that will become its axon and dendrites.
• A specialized enlargement, the growth cone, forms the tip
of each extending axon and is involved in finding the
correct route and final target for the process.
• As the axon grows, it is guided along the surfaces of other
cells, most commonly glial cells.

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Development of the Nervous System
• Which route the axon follows depends largely on attracting,
supporting, deflecting, or inhibiting influences exerted by
cell adhesion molecules and soluble neurotrophic factors
(growth factors for neural tissue) in the extracellular fluid
surrounding the growth cone or its distant target.
• Once the target of the advancing growth cone is reached,
synapses form.
• During these early stages of neural development, which
occur during all trimesters of pregnancy and into infancy,
alcohol and other drugs, radiation, malnutrition, and viruses
can exert effects that cause permanent damage to the
developing fetal nervous system.
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 Development of the Nervous System

• Early in development, the brain has much greater potential for

remodeling in response to stimulation or injury than in the
adult brain, a characteristic known as plasticity.
• The basic shapes and locations of major neuronal circuits in the
mature central nervous system do not change once formed.
• The creation and removal of synaptic contacts begun during
fetal development continue, however, though at a slow pace
throughout life as part of normal growth, learning, and aging.

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Injury of the Nervous System
• If axons are severed, they can repair themselves and restore
significant function provided that the damage occurs outside
the central nervous system and does not affect the neuron’s cell
body.
• After such an injury, the axon segment that is separated from
the cell body degenerates. The part of the axon still attached to
the cell body then gives rise to a growth cone, which grows out
to the effector organ so that function is sometimes restored.
• Return of function following a peripheral nerve injury is
delayed because axon regrowth proceeds at a rate of only 1 mm
per day.

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Injury of the Nervous System
• Spinal injuries typically crush rather than cut the tissue, leaving
the axons intact.
• In this case, the problem is apoptosis of the oligodendrocytes.
This results in loss of the myelin coat and the axons cannot
transmit information effectively.
• Severed axons within the CNS may grow small new extensions
but no significant regeneration of the axon occurs across the
damaged site, and there are no well-documented reports of
significant return of function.

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New Attempts to Repair Nervous System
Damage
• Researchers are trying a variety of ways to provide an
environment that will support axonal regeneration in the
central nervous system.
– They are creating tubes to support regrowth of the severed
axons, redirecting the axons to regions of the spinal cord that
lack growth-inhibiting factors, preventing apoptosis of the
oligodendrocytes so myelin can be maintained, and supplying
neurotrophic factors that support recovery of the damaged
tissue.
• Medical researchers are also attempting to restore
function to damaged or diseased brains by implanting
stem cells, pieces of fetal brain or other brain tissues to
replace the lost functions.
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Synapses
Synapses can use
both chemical and
electrical stimuli to
pass information.

Synapses can also

be inhibitory or
excitatory
depending on the
signal/
neurotransmitter
being transmitted.

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Basic Principles of Electricity

17
The Resting
Membrane
Potential

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19
 Membrane Potentials
• Different cells have different resting membrane
potentials. Neurons have a resting membrane
potential generally in the range of –40 to –90 mV.
• Changes in potential are due to movement of ions.

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 Establishing Membrane Potential
• First, the action of the Na+/K+-ATPase pump sets up the concentration
gradients for Na+ and K+
• Then there is a greater flux of K + out of the cell than Na+ into the cell. This is
because in a resting membrane there are a greater number of open K+ channels
than there are Na+ channels. Because there is greater net efflux than influx of
positive ions during this step, a significant negative membrane potential
develops, with the value approaching that of the K + equilibrium potential.
• In the steady-state, the flux of ions across the membrane reaches a dynamic
balance. Because the membrane potential is not equal to the equilibrium
potential for either ion, there is a small but steady leak of Na + into the cell and
K+ out of the cell.
• The concentration gradients do not dissipate over time, however, because ion
movement by the Na+/K+-ATPase pump exactly balances the rate at which the
ions leak through open channels.

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Establishing the Resting Membrane Potential

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 Terminology
• When talking about action potentials and graded potentials we
use these terms: depolarization, repolarization,
hyperpolarization.
• These terms are all relative to the resting membrane potential
(RMP).
• Depolarization is the potential moving from RMP to less
negative values.
• Repolarization is the potential moving back to the RMP.
• Hyperpolarization is the potential moving away from the RMP
in a more negative direction.

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24
Depolarization

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 Action Potentials
• Action potentials are generally very rapid (as brief as
1–4 milliseconds) and may repeat at frequencies of
several hundred per second.
• The ability to generate action potentials is known as
excitability. This ability is possessed by neurons,
muscle cells and some other types of cells.
• An action potential is a large change in membrane
potential and is an “all or none” response.

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 Action Potential Membrane Depolarization

• In order to cause an action potential, a cell must utilize

several types of ion channels.
• Ligand-gated channels and mechanically gated channels
often serve as the initial stimulus for an action potential.
• Voltage-gated channels give a membrane the ability to
undergo action potentials by allowing the rapid
depolarization and repolarization phases of the response.
• There are dozens of different types of voltage-gated ion
channels, varying by which ion they conduct (e.g., Na+,
K+, Ca2+, or Cl-) and in how they behave as the membrane
voltage changes.
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Voltage-Gated Na+& K+ Channels

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Mechanism
of an Action
Potential

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Control Mechanisms of an Action Potential

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 Clinical Effects of Action Potential
Inhibition
• The generation of action potentials is prevented by local
anesthetics such as procaine (Novocaine®) and lidocaine
(Xylocaine®) because these drugs block voltage-gated Na+
channels.
• Without action potentials, graded signals generated in the
periphery—in response to injury, for example—cannot reach
the brain and give rise to the sensation of pain.
• Some animals produce toxins that work by interfering with
nerve conduction in the same way that local anesthetics do.
For example, the puffer fish produces tetrodotoxin, that block
voltage-gated Na+ channels.

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 Refractory Period
• There are two types of refractory periods that cells undergo following an
action potential: Absolute and Relative.
• The absolute refractory period is during the action potential;
a second stimulus, no matter how strong, will not produce a second action
potential .
• This occurs during the period when the voltage-gated Na+ channels are
either already open or have proceeded to the inactivated state during the
first action potential.
• Following the absolute refractory period, there is an interval during which
a second action potential can be produced, but only if the stimulus strength
is considerably greater than usual. This is the relative refractory period.

32
 Refractory Period
• The refractory periods limit the number of action
potentials an excitable membrane can produce in a given
period of time.
• Most neurons respond at frequencies of up to 100 action
potentials per second, and some may produce much
higher frequencies for brief periods.
• Refractory periods contribute to the separation of these
action potentials so that individual electrical signals pass
down the axon.
• The refractory periods also are the key in determining the
direction of action potential propagation.
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Refractory Period

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 Action Potential Propagation
• Action potentials in neurons are unidirectional (can only go
forward down the axon, since the space behind is in its
refractory period).
• In skeletal muscle cells the action potentials are initiated near
the middle of the cells and propagate toward the two ends.
• The velocity with which an action potential propagates along a
membrane depends upon fiber diameter and whether or not the
fiber is myelinated.
• The larger the fiber diameter, the faster the action potential
propagates, because a large fiber offers less resistance to local
current; more ions will flow in a given time.

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 Action Potential Propagation

• Myelin is an insulator that makes it more difficult for

charge to flow between intracellular and extracellular
fluid compartments.
• Action potentials occur only at the nodes of Ranvier,
where the myelin coating is interrupted and the
concentration of voltage-gated Na+ channels is high.
• Thus, action potentials jump from one node to the next as
they propagate along a myelinated fiber, and for this
reason such propagation is called saltatory conduction.

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 Action Potential Propagation

• Propagation via saltatory conduction is faster than

propagation in non myelinated fibers of the same axon
diameter.
• Moreover, because ions cross the membrane only at the
nodes of Ranvier, the membrane pumps need to restore
fewer ions.
• Myelinated axons are metabolically more efficient than
unmyelinated ones.
• Myelin adds speed, reduces metabolic cost, and saves
room in the nervous system because the axons can be
thinner.
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Action
Potential
Propagation

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Saltatory Conduction

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Synapses

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 Synapses

• Synapses are junctions between two neurons.

• They can be chemical or electrical
• In an electrical synapse, the electrical activity
of the presynaptic neuron affects the electrical
activity of the postsynaptic neuron.
• Chemical synapses utilize neurotransmitters.

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 Functional Anatomy of Synapses

• Electrical
– Pre- and post-synaptic cells are connected by gap
junctions.
• Chemical
– Pre-synaptic neurons release neurotransmitter from
their axon terminals.
– Neurotransmitter binds to receptors on post-
synaptic neurons.

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Anatomy of a Chemical Synapse

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Mechanisms of Neurotransmitter Release

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 Docking of Vesicles and Release of
Neurotransmitters
• Neurotransmitters are produced and stored in
vesicles at the axon terminal.
• When the cell is stimulated, the intracellular
Ca2+ levels increase and stimulate the vesicles
to translocate and bind to the plasma
membrane via the SNARE proteins.
• The neurotransmitter is then released via
exocytosis.
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 Removal of Neurotransmitter

• To terminate the signal in a chemical synapse

the neurotransmitter must be removed. This is
accomplished by:
1. Diffusion of the transmitter from the cleft
2. Degradation of the transmitter by enzymes
3. Reuptake into the pre-synaptic cells for reuse

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 Activation of the Postsynaptic Cell

• Excitatory chemical synapses generate an excitatory

postsynaptic potential (EPSP).
• EPSPs serve to bring the membrane potential closer to
threshold for generating an action potential
• Inhibitory chemical synapses generate an inhibitory
postsynaptic potential (IPSP).
• IPSPs make the cell’s membrane potential more negative,
making it harder to generate an action potential.

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Excitatory Postsynaptic Potential

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Inhibitory Postsynaptic Potential

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Synaptic Integration

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 Axo-Axonic Synapse

Neuron A is exerting a pre-synaptic effect on the synapse between B and C.

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 Modification of Synaptic Transmission by
Drugs and Disease
• Drugs act by interfering with or stimulating normal processes
in the neuron involved in neurotransmitter synthesis, storage,
and release, and in receptor activation.

• Diseases can also affect synaptic mechanisms.

• Examples: Clostridium tetani(tetanus toxin) prevents vesicle fusion
with the membrane, inhibiting neurotransmitter release and causes
increased muscle contraction.
• Clostridium botulinum bacilli toxin (botulism), interferes with actions
of SNARE proteins at excitatory synapses that activate muscles;
botulism is characterized by muscle paralysis.
• Low doses of botulinum toxin (Botox) are injected therapeutically
to treat a number of conditions, including facial wrinkles, severe
sweating, uncontrollable blinking, misalignment of the eyes, and
others.
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Drug Effects

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54
 Acetylcholine
• Acetylcholine (ACh) is found in PNS and CNS.
Neurons that use ACh as the primary neurotransmitter
are known as cholinergic neurons.
• ACh acts at muscarinic (G protein coupled) or nicotinic
(ion channels) receptors. Nicotinic receptors are found
at the neuromuscular junctions of skeletal muscles.
• ACh is produced in the presynaptic axon by the enzyme
choline acetyl transferase (CAT) as follows:
• Acetyl CoA + choline acetylcholine + CoA
• Degradation of ACh occurs in synaptic cleft and is done
by the enzyme acetylcholinesterase (AChE) as follows:
• Acetylcholine  acetate + choline
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 Cholinergic System Issues
• Some chemical weapons, such as the nerve gas Sarin, inhibit
acetylcholinesterase, causing a buildup of ACh in the
synaptic cleft.
• Overstimulation of postsynaptic ACh receptors causes
uncontrolled muscle contractions, ultimately leading to
receptor desensitization and paralysis.
• Nicotinic receptors in the brain are important in cognitive
functions and behavior. The presence of nicotinic receptors
on presynaptic terminals in reward pathways of the brain
explains why tobacco products are among the most highly
addictive substances known.
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 Alzheimer’s Disease
• Neurons associated with the ACh system degenerate in people
with Alzheimer’s disease. Alzheimer’s disease affects 10 to 15
percent of people over age 65, and 50 percent of people over
age 85.
• Because of the degeneration of cholinergic neurons, this
disease is associated with a decreased amount of ACh in
certain areas of the brain and even the loss of the postsynaptic
neurons that would have responded to it.
• These defects and those in other neurotransmitter systems that
are affected in this disease are related to the declining
language and perceptual abilities, confusion, and memory loss
that characterize Alzheimer’s victims.
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 Biogenic Amines
• Biogenic amine neurotransmitters are made from amino acids as
follows:
• Catecholamines
• Made from tyrosine:
• Dopamine
• Norepinephrine
• Epinephrine

• Made from tryptophan:

• Serotonin

• Made from histidine:

• Histamine

• The enzymes which degrade the biogenic amine

neurotransmitters are:
• Monoamine oxidase (MAO)
• Catechol-o-methyltransferase
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Synthesis of Catecholamines

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 Adrenergic Receptors

• Adrenergic receptors are utilized by the neurotransmitters

Norepinephrine (NE) and Epinephrine (Epi). NE is found in both the
CNS and PNS but Epi is found mainly in the PNS. Adrenergic comes
from historical use as Noradrenaline (NA) and adrenaline for NE and
Epi, respectively.
• Adrenergic receptors are G protein coupled and generally are linked to
second messenger signal transduction pathways.
• Alpha adrenergic receptors
‒ Alpha1 (α1)
‒ Alpha2
• Beta adrenergic receptors
‒ Beta1 (β1)
‒ Beta2
‒ Beta3 60
 Parkinson’s Disease
• This disease involves the loss of dopamine-releasing
neurons.
• Symptoms include persistent tremors, head nodding and pill
rolling behaviors, a forward bent walking posture, shuffling
gait, stiff facial expressions and they are slow in initiating
and executing movement.
• The cause is not clearly understood, but loss of the
dopamine neurons is critical.
• It is currently treated with the drug L-Dopa in the initial
stages to alleviate symptoms. This is often given with the
drug deprenyl (which prevents the breakdown of L-Dopa).
This is NOT curative. These drugs only treat the symptoms.
• Experimental treatments currently include deep brain
stimulation by surgically implanting electrodes, gene
therapy and fetal/stem cell transplants.
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 Serotonin
• Main CNS location
• Brainstem (1-2%)
• Drugs
• Selective serotonin reuptake inhibitors (SSRI) are used for
depression.
• LSD stimulates a subtype serotonin receptor.
• Functions
• Regulating sleep
• Emotions
• Excessive serotonin release by gut increases motility, causing
diarrhea
• Regulates cell growth
• Vascular smooth muscle cell contraction

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 Histamine

• CNS neurotransmitter whose major location is the

hypothalamus
• Histamine is commonly known for paracrine
actions.
• Histamine is also found in the peripheral system. It
is involved in allergic reactions, nerve
sensitization, and acid production in the stomach.

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 Amino Acid Neurotransmitters
• Amino acid neurotransmitters at excitatory
synapses are:
• Aspartate
• Glutamate

• Amino acid neurotransmitters at inhibitory synapses

are:
• Glycine
• GABA

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 Glutamate
• Glutamate is estimated to be the primary
neurotransmitter at 50 percent of the excitatory
synapses in the CNS.
• There are 2 types of receptors:
– Metabotropic glutamate receptors
(G-protein Coupled receptors)
– Ionotropic glutamate receptors
• AMPA receptors (identified by their binding to
a-amino-3 hydroxy-5 methyl-4 isoxazole proprionic
acid)
• NMDA receptors (which bind N-methyl-D-aspartate)

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 Glutamate

• Cooperative activity of AMPA and NMDA receptors has been

implicated in a phenomenon called long-term potentiation
(LTP).
• This mechanism couples frequent activity across a synapse
with lasting changes in the strength of signaling across that
synapse, and is thus thought to be a cellular process
underlying learning and memory.

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Glutamatergic Synapses

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 Glutamate Actions
• Step 1. Presynaptic neuron fires action potentials.
• Step 2. Glutamate is released from presynaptic terminals.
• Step 3. Glutamate binds to both AMPA and NMDA receptors on
postsynaptic membranes.
• Step 4. Depolarizing EPSP of the postsynaptic cell mediated via AMPA
channels (Na+).
• Step 5. The depolarization through the AMPA channels allows the
magnesium ion blocking the NMDA channels to move and activate the
channel. NMDA-receptor channels mediate a substantial Ca 2+ flux.
• Step 6. Calcium enters the cell.
• Step 7. Calcium ions activate second-messenger cascade in the
postsynaptic cell that includes persistent activation of two different protein
kinases, and which increases the sensitivity of the postsynaptic neuron to
glutamate.
• Step 8. This second-messenger system can also activate long-term
enhancement of presynaptic glutamate release via retrograde signals that
have not yet been identified.
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 NMDA Receptors
• NMDA receptors have also been implicated in mediating excitotoxicity.
• This is a phenomenon in which the injury or death of some brain cells
(due, for example, to blocked or ruptured blood vessels) rapidly spreads to
adjacent regions.
• When glutamate-containing cells die and their membranes rupture, the
flood of glutamate excessively stimulates AMPA and NMDA receptors on
nearby neurons.
• The excessive stimulation of those neurons causes the accumulation of
toxic levels of intracellular Ca2+, which in turn kills those neurons and
causes them to rupture, and the wave of damage progressively spreads.
• Recent experiments and clinical trials suggest that administering NMDA
receptor antagonists may help minimize the spread of cell death following
injuries to the brain.

69
 GABA
• GABA (gamma-aminobutyric acid) is the major inhibitory
neurotransmitter in the brain.
• Although it is not one of the 20 amino acids used to build
proteins, it is classified with the amino acid neurotransmitters
because it is a modified form of glutamate.
• GABA neurons in the brain are small interneurons that
dampen activity within neural circuits. Postsynaptically,
GABA may bind to ionotropic or metabotropic receptors.
• The ionotropic receptor increases Cl- flux into the cell,
resulting in hyperpolarization of the postsynaptic membrane.

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 GABA
• In addition to the GABA binding site, this receptor has several
additional binding sites for other compounds, including
steroids, barbiturates, and benzodiazepines.
• Benzodiazepine drugs such as alprazolam (Xanax®) and
diazepam (Valium®) reduce anxiety, guard against seizures,
and induce sleep, by increasing Cl- flux through the GABA
receptor.
• Synapses that use GABA are also among the many targets of
the ethanol found in alcoholic beverages.

71
 GABA and Alcohol
• Ethanol stimulates GABA synapses and simultaneously
inhibits excitatory glutamate synapses, with the overall effect
being global depression of the electrical activity of the brain.
• Thus, as a person’s blood alcohol content rises, there is a
progressive reduction in overall cognitive ability, along with
reduced sensory perception (hearing and balance in particular),
motor incoordination, impaired judgment, memory loss, and
unconsciousness.
• Very high doses of ethanol are sometimes fatal, due to
suppression of brainstem centers responsible for regulating the
cardiovascular and respiratory systems.

72
 Neuropeptides
• Examples include:
• Endogenous opioids
• Enkephalins
• Endorphins
• Morphine and codeine are synthetic opioids that are used as
analgesics (pain reducers).
• Substance P
• Released by afferent neurons that relay sensory
information into the central nervous system.
• It is known to be involved in pain sensation.

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 Gas Neurotransmitters
• Gases are not released by exocytosis of presynaptic vesicles, nor
do they bind to postsynaptic plasma membrane receptors. They
are produced by enzymes in axon terminals (in response to Ca 2+
entry), and simply diffuse from their sites of origin in one cell
into the intracellular fluid of other neurons or effector cells, where
they bind to and activate proteins.
• Examples:
 Nitric oxide (NO) is produced by nitric oxide synthetase (eNOS,
nNOS, iNOS) and undergoes very rapid degradation. Once in the
target cell, it activates cGMP signaling pathways.
 Carbon monoxide and hydrogen sulfide are also emitted by
neurons as signals.

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Structure of the Nervous System

75
Central Nervous System: Brain

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 Forebrain
• The cerebrum consists of the right and left cerebral
hemispheres as well as certain other structures on the
underside of the brain. The central core of the forebrain is
formed by the diencephalon.
• The cerebral hemispheres consist of the cerebral cortex, an
outer shell of gray matter composed primarily of cell bodies
that give the area a gray appearance, and an inner layer of
white matter, composed primarily of myelinated fiber tracts.
• This overlies cell clusters, which are also gray matter and are
collectively termed the subcortical nuclei. The fiber tracts
consist of the many nerve fibers that bring information into the
cerebrum, carry information out, and connect different areas
within a hemisphere.
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78
 Forebrain: Cerebral Cortex

• The cortex layers of the left and right cerebral hemispheres, although
largely separated by a deep longitudinal division, are connected by a
massive bundle of nerve fibers known as the corpus callosum.
• The cortex of each cerebral hemisphere is divided into four lobes:
– Frontal
– Parietal
– Occipital
– Temporal
• The cortex is 3 mm in thickness but is highly folded. This results in an area
containing cortical neurons that is four times larger than it would be if
unfolded, without appreciably increasing the volume of the brain.

79
 Forebrain: Cerebral Cortex
• This folding results in the characteristic external appearance of
the human cerebrum, with its sinuous ridges separated by
grooves.
• The cells of the human cerebral cortex are organized in six
distinct layers, composed of two basic types: pyramidal cells
(named for the shape of their cell bodies) and nonpyramidal
cells.
• The pyramidal cells form the major output cells of the
cortex, sending their axons to other parts of the cortex and to
other parts of the central nervous system.
• Nonpyramidal cells are mostly involved in receiving inputs
into the cortex and in local processing of information.

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 Forebrain: Cerebral Cortex
• The cerebral cortex is the integrating area of the nervous
system.
• In the cerebral cortex, basic afferent information is collected
and processed into meaningful perceptual images, and control
over the systems that govern the movement of the skeletal
muscles is refined.

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 Forebrain: Diencephalon

• The diencephalon contains the thalamus, hypothalamus, and

epithalamus.
• The thalamus is a collection of several large nuclei that serve
as synaptic relay stations and important integrating centers for
most inputs to the cortex, and plays a key role general arousal.
• The thalamus also is involved in focusing attention. For
example, it is responsible for filtering out extraneous sensory
information.

82
 Forebrain: Diencephalon
• The hypothalamus lies below the thalamus and is on the
undersurface of the brain and it contains different cell groups
and pathways that form the master command center for neural
and endocrine coordination.
• Behaviors having to do with preservation of the individual (for
example, eating and drinking) and preservation of the species
(reproduction) are among the many functions of the
hypothalamus.
• The hypothalamus lies directly above and is connected by a
stalk to pituitary gland, an important endocrine structure that
the hypothalamus regulates.

83
 Forebrain: Diencephalon

• The epithalamus is a small mass of tissue that includes the

pineal gland, which has a role in regulating biological
rhythms.
• Some of the forebrain areas, consisting of both gray and white
matter, are also classified together in a functional system
called the limbic system.
• Structures within the limbic system are associated with
learning, emotional experience and behavior, and a wide
variety of visceral and endocrine functions.

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Limbic System

85
 Cerebellum
• Although the cerebellum does not initiate voluntary
movements, it is an important center for coordinating
movements and for controlling posture and balance.
• To carry out these functions, the cerebellum receives
information from the muscles and joints, skin, eyes
and ears, viscera, and the parts of the brain involved
in control of movement.
• Although the cerebellum’s function is almost
exclusively motor, it is implicated in some forms of
learning.
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 Brainstem
• All the nerve fibers that relay signals between the forebrain,
cerebellum, and spinal cord pass through the brainstem.
• Running through the core of the brainstem and consisting of
loosely arranged neuron cell bodies intermingled with bundles
of axons, is the reticular formation, the one part of the brain
absolutely essential for life.
• It receives and integrates input from all regions of the central
nervous system and processes a great deal of neural
information. The reticular formation is involved in motor
functions, cardiovascular and respiratory control, and the
mechanisms that regulate sleep and wakefulness and focus of
attention.
87
 Brainstem
• Some reticular formation neurons are clustered together,
forming brainstem nuclei and integrating centers.
• These include the cardiovascular, respiratory, swallowing, and
vomiting centers. The reticular formation also has nuclei
important in eye-movement control and the reflex orientation
of the body in space.
• The brainstem contains nuclei involved in processing
information for 10 of the 12 pairs of cranial nerves. These are
the peripheral nerves that connect directly with the brain and
innervate the muscles, glands, and sensory receptors of the
head, as well as many organs in the thoracic and abdominal
cavities.

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Cranial Nerves

89
 Spinal Cord
• The spinal cord lies within the bony vertebral column and is a
slender cylinder of soft tissue about as big around as the little
finger.
• The central butterfly-shaped area of gray matter is composed
of interneurons, the cell bodies and dendrites of efferent
neurons, the entering axons of afferent neurons, and glial cells.
• The regions of gray matter projecting toward the back of the
body are called the dorsal horns, whereas those oriented
toward the front are the ventral horns.
• The gray matter is surrounded by white matter, which consists
of groups of myelinated axons.

90
Central Nervous System: Spinal Cord

91
 Spinal Cord
• These groups of fiber tracts run longitudinally through the
cord, some descending to relay information from the brain to
the spinal cord, others ascending to transmit information to the
brain. Pathways also transmit information between different
levels of the spinal cord.
• Groups of afferent fibers that enter the spinal cord from the
peripheral nerves enter on the dorsal side of the cord via the
dorsal roots. Small bumps on the dorsal roots, the dorsal root
ganglia, contain the cell bodies of these afferent neurons.
• The axons of efferent neurons leave the spinal cord on the
ventral side via the ventral roots. A short distance from the
cord, the dorsal and ventral roots from the same level combine
to form a spinal nerve, one on each side of the spinal cord.
92
 Peripheral Nervous System

• Neurons in the peripheral nervous system transmit signals

between the central nervous system and receptors and
effectors in all other parts of the body.

• The peripheral nervous system has 43 pairs of nerves: 12 pairs

of cranial nerves and 31 pairs that connect with the spinal cord
as the spinal nerves.
• The 31 pairs of spinal nerves are designated by the vertebral
levels from which they exit: cervical (8), thoracic (12), lumbar
(5), sacral (5), and coccygeal (1).

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 Peripheral Nervous System

• The eight pairs of cervical nerves control the muscles and

glands and receive sensory input from the neck, shoulders,
arms, and hands.
• The 12 pairs of thoracic nerves are associated with the chest
and upper abdomen.
• The five pairs of lumbar nerves are associated with the lower
abdomen, hips, and legs.
• The five pairs of sacral nerves are associated with the genitals
and lower digestive tract. (A single pair of coccygeal nerves
associated with the tailbone brings the total to 31 pairs.)

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 Peripheral Nervous System

• These peripheral nerves can contain nerve fibers that are the
axons of efferent neurons, afferent neurons, or both.
• All the spinal nerves contain both afferent and efferent fibers,
whereas some of the cranial nerves contain only afferent fibers
or only efferent fibers.
• Efferent neurons carry signals out from the central nervous
system to muscles or glands. The efferent division of the
peripheral nervous system is more complicated than the
afferent, being subdivided into a somatic nervous system and
an autonomic nervous system.

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Spinal Nerves

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97
 Autonomic Nervous System
• The gastrointestinal tract has the enteric nervous system, and
although often classified as a subdivision of the autonomic
efferent nervous system, it also includes sensory neurons and
interneurons.

• Anatomical and physiological differences within the

autonomic nervous system are the basis for its further
subdivision into sympathetic and parasympathetic divisions.

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 Autonomic Nervous System

• Sympathetic division is also called the thoracolumbar division,

has short pre-ganglionic and long post-ganglionic synapses.
The major neurotransmitters are ACh at the pre-ganglionic
synapse and usually NE and Epi at the post-ganglionic
synapse. This is the “Flight or Fight” response system.
• Parasympathetic is called the craniosacral division, it has long
pre-ganglionic and short post-ganglionic synapses. The major
neurotransmitter is ACh at both pre- and post-ganglionic
synapses. This is the “Rest and Digest” system.

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Autonomic nervous system

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ANS vs SNS

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 Physical Support of the CNS
• Bone serves to support and to protect the structures of the
CNS and PNS.
• Cranium
• Vertebrae

• Meninges are the membranes that line the structures and add
additional support and protection.
• Dura mater
• Arachnoid mater
• Pia mater

• Cerebrospinal fluid (CSF) protects and cushions the

structures.
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 The Meninges

• There are three layers of the meninges. From external to

internal they are: dura mater, arachnoid mater, and pia mater.
• The job of the meninges is to:
1. Cover and protect the CNS
2. Protect blood vessels and enclose the venous sinuses
3. Contain cerebrospinal fluid
4. Form partitions in the skull

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 The Meninges
• The subarachnoid space is filled with CSF and contains the
largest blood vessels serving the brain. In the superior sagittal
sinus the arachnoid villi absorb the CSF into the venous blood
system.
• The pia mater clings to the brain and contains a network of
blood vessels.
• Meningitis is an inflammation of the meninges and is a
serious threat to the brain since bacterial or viral meningitis
can spread to the CNS. If the brain itself is inflamed it is
called encephalitis. Meningitis is usually diagnosed by
examining the CSF obtained via a lumbar puncture for
microbes or viruses.
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 Cerebrospinal Fluid (CSF)

• CSF is the extracellular fluid of the CNS and it is

secreted by ependymal cells of the choroid plexus. It
circulates through the subarachnoid space and
ventricles and is reabsorbed by arachnoid villi.
• Total volume of CSF present at any given time is
approximately 125–150 mL. The choroid plexus
produces 400–500 mL/day, so the entire contents are
recycled three times a day.
• This is important to maintaining a stable and optimal
environment.

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Cerebrospinal Fluid

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 Hydrocephalus

• Hydocephalus is “water on the brain”.

• It is an accumulation of CSF in the brain that
is often caused by tumors.
• In newborns it results in enlargement of the
head. In adults (whose skull bones have fused)
it puts pressure on the brain and causes brain
damage. It is treated by inserting a shunt to
drain the fluid.
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 Blood-Brain Barrier
• This is a protective mechanism that helps maintain a
stable environment for the brain.

• Substances in the brain’s capillaries are separated

from the extracellular space by the continuous
endothelium of the capillary walls and a thick basal
lamina surrounding the capillaries. The “feet” of the
astrocytes surrounding the capillaries also contribute.

• These capillaries are the least permeable ones in the

body. This barrier is very selective. Things that are
highly lipid-soluble cross easily.
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 Cerebrovascular Accidents
• Otherwise known as a stroke, CAs can be caused by a
decreased blood supply or a hemorrhage.
• An ischemic stroke is one caused by the occlusion of cerebral
arteries, usually by a blood clot that blocks an artery or by the
rupture of an atherosclerotic plaque . If it is detected early
enough, “clot busting” drugs (TPA-tissue plasminogen
activator) can be administered. This dissolves the clot and
restores blood flow to the area.
• A hemorrhagic stroke is one where the blood vessel has
ruptured. The best treatment available is to try to cauterize the
vessel (if possible) and to alleviate the pressure on the brain
caused by the bleeding.
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 Head Injuries
• Head injuries are the leading cause of accidental death in North
America.
• Hard blows to the head result in a coup injury (the site of the blow)
as well as a contrecoup (where the brain hits the other side of the
skull).
• A concussion is an alteration of brain function following a blow to
the head. This is usually temporary and the victim can show signs of
dizziness, or may lose consciousness. Multiple concussions can
cause cumulative damage (boxers and football player have to be
carefully monitored for this).
• A contusion is bruising of the brain. This always causes some
permanent damage. If it occurs in the brainstem it can cause coma or
death.
• Head blows may also result in subdural or subarachnoid
hemorrhages which can cause permanent neurological damage and
death.
• Cerebral edema can also be caused by a blow to the head. This can
cause permanent damage or death by putting pressure on the brain.
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