MODULE 11.

1: OVERVIEW OF THE NERVOUS SYSTEM

• Nervous system – controls our perception and experience of world
 Directs voluntary movement
 Seat of consciousness, personality, learning, and memory
 Regulates many aspects of homeostasis along with endocrine system, including:
o respiratory rate
o blood pressure
o body temperature
o sleep/wake cycle
o blood pH

Understand how the nervous system is organized functionally and structurally.

Anatomical Divisions of the Nervous System:
• Divided anatomically into central nervous system (CNS) and peripheral nervous system (PNS):
 CNS – includes brain and spinal cord
o Brain – made up of billions of nerve cells or neurons; protected by bones of skull
o Spinal cord begins at foramen magnum and continues through vertebral foramina
of first cervical to first or second lumbar vertebra
• Made up of millions of neurons; much fewer than brain
• Enables brain to communicate with most of body below head and neck
 PNS – consists of all nerves in body outside protection of skull and vertebral column
o Nerves consist of axons of neurons bundled together with blood vessels & CT; carry
signals to & from CNS; classified based on origin or destination
• 12 pairs of nerves traveling back to or from brain; called cranial nerves
• 31 pairs of nerves traveling back to or from spinal cord; called spinal nerves

The organs of the CNS are the brain and spinal cord.
The organs of the PNS are the cranial and spinal nerves.

The sensory function is gathering information about the internal or external environments of the body.
The integrative function is determining how to respond to sensory information.
The motor function is carrying out the actions determined by integration.

The somatic division carries sensory information from the muscles, bones and joints, and skin.
The visceral division carries sensory information from the visceral organs.
The somatic motor division is under conscious control and controls skeletal muscle. The ANS is not
under conscious control and controls smooth muscles and glands.
Understand how the nervous system is organized functionally and structurally.
Functional Divisions of the Nervous System:
• Nervous system performs millions of tasks simultaneously every second; fall into 3 functional
categories: sensory, integrative, or motor:
 Sensory functions – gather information about internal and external environments of body;
input is gathered by sensory or afferent division of PNS; further divided into somatic and
visceral divisions; Sensory input from both divisions is carried from sensory receptors to
spinal cord and/or brain by spinal and cranial nerves
o Somatic sensory division – consists of neurons that carry signals from skeletal
muscles, bones, joints, and skin; also transmits signals from organs of vision,
hearing, taste, smell, and balance; sometimes called special sensory division
o Visceral sensory division – consists of neurons that transmit signals from viscera
(organs) such as heart, lungs, stomach, kidneys, and urinary bladder

 Integrative functions – analyze and interpret incoming sensory information and determine
an appropriate response
o 99% of integrated sensory information is subconsciously disregarded as
unimportant
o Remaining sensory stimuli that CNS does respond to generally leads to a motor
response

 Motor functions – actions performed in response to integration; performed by motor or

efferent division of PNS; can be further subdivided into somatic and autonomic divisions,
based on organs that neurons contact
o Motor/efferent division – consists of motor neurons that carry out motor
functions; travel from brain and spinal cord via cranial and spinal nerves; organs
that carry out effects of nervous system are commonly called effectors.
Subdivisions are:
• Somatic motor division consists of neurons that transmit signals to skeletal
muscle; under voluntary control (aka voluntary motor division)
• Autonomic nervous system (ANS) or visceral motor division
» Consists of neurons that carry signals to thoracic and abdominal
viscera; critical for maintaining homeostasis of body’s internal
environment
» Regulates secretion of certain glands, contraction of smooth muscle,
and contraction of cardiac muscle in heart; involuntary (aka
involuntary motor division)
 MODULE 11.2 NERVOUS TISSUE

Neurons:
 Axolemma – PM that surrounds axon & its cytoplasm or axoplasm
 Substances may travel through axoplasm using one of two types of transport, which are
together termed axonal transport or flow
o Slow axonal transport – transports substances like cytoskeleton proteins from cell
body through axon at a rate of 1–3 mm/day
o Fast axonal transport – requires motor proteins and consumes ATP; vesicles and
membrane-bound organelles travel more quickly back toward (retrograde
transport) or away from (anterograde transport) cell body at a maximum rate of
200 mm/day & 400 mm/day respectively

Poliovirus and Retrograde Axonal Transport:

• Poliomyelitis – caused by poliovirus; infection that impacts CNS and especially spinal cord; can
result in deformity and paralysis
• No cure exists, but polio can be easily prevented by vaccination
• Virus accesses CNS by first entering muscle cells; then passes into motor neurons at
neuromuscular junction; travels length of axon by retrograde axonal transport until reaching
spinal cord
• Other viruses (herpes simplex, rabies) and toxins (tetanus) also have ability to invade via this
method
Understand how the neurons are organized structurally and functionally.
Neurons:
• Neurons have three main functional regions:
 Receptive region – includes dendrites and cell body
 Conducting region – includes axon
 Secretory (transmissive) region – includes axon terminal (synaptic knob)
• Neurons can be classified according to structural features into 3 groups:
 Multipolar neurons – w a single axon & multiple dendrites, makeup > 99% of all neurons.
 Bipolar neurons – with one axon and one dendrite and a cell body between them; found
in eye and olfactory epithelium in nasal cavity
 Pseudounipolar neurons – have only 1 fused axon that extends from cell body & divides
into 2 processes: one process carries sensory information from sensory receptors to cell
body; other process carries sensory info from cell body to spinal cord; sensory neurons
that carry information related to pain, touch, and pressure
• Neurons can also be classified into three functional groups (Table 11.1):
 Sensory or afferent neurons – carry information toward CNS; neuron cell bodies in PNS
receive information from sensory receptors and relay information via axons to brain or
spinal cord; usually pseudounipolar or bipolar
 Interneurons or association neurons – relay information within CNS between sensory and
motor neurons; make up most of neurons in body; multipolar, communicating with many
other neurons
 Motor or efferent neurons – carry information away from cell body in CNS to muscles and
glands; mostly multipolar

• Specific neuron components group together:

 CNS:
o Nuclei – clusters of neuron cell bodies
o Tracts – bundles of axons
 PNS:
o Ganglia – clusters of neuron cell bodies
o Nerves – bundles of axons

Neuroglia:
• Neuroglia or neuroglial cells not only provide structural support and protection for neurons but
also maintain their environment (Fig 11.6, 11.7)
 Able to divide and fill in space left behind when a neuron dies; form of each type of
neuroglial cell is specialized for its function, another ex of the Structure-Funx Principle
 4 types reside in CNS:
o Astrocytes
o Oligodendrocytes
o Microglia
o Ependymal cells
 2 types reside in PNS:
o Schwann cells
o Satellite cells
 • Astrocytes – large star-shaped cells whose many processes terminate in structures called end-
feet; function to:
 Anchor neurons & blood vessels in place; help define & maintain 3-D structure of brain
 Facilitate transport of nutrients & gases btwn blood vessels and neurons; regulate
extracellular environment of brain
 Assist in formation of blood-brain barrier; protective structure that surrounds capillary
endothelial cells and makes them impenetrable to most polar compounds and proteins
 Repair damaged brain tissue by rapid cell division* (mitotically active- so actrocytes are
usually the culprit of tumor in brain- astrocytoma)
• Oligodendrocytes – also found in CNS; have radiating processes with flattened sacs that wrap
around axons of nearby neurons to form myelin
• Microglia – small and scarce cells; activated by injury into wandering phagocytic cells within
CNS; ingest disease-causing microorganisms, dead neurons, and cellular debris.
 Immune system cells!
• Ependymal cells – ciliated cells that line hollow spaces found within CNS (brain and
spinal cord); function to manufacture & circulate CSF (cerebrospinal fluid).
• Schwann cells – encircle axons found in PNS to provide them with myelination. (Wrap their
whole PM around the axon to insulate axon. Where axon is myelinated is called an internode.
Between the internodes are Nodes of Ranvier.)
• Satellite cells – found surrounding cell bodies of neurons in PNS to provide supportive
functions (still not well defined)
Astrocyte and satellite cells are similar. Oligodendrocyte and Schwann cells are similar.
The Myelin Sheath
Myelin Sheath – composed of repeating layers of PM of Schwann cell or oligodendrocyte in PNS and
CNS respectively (Fig 11.8, 11.9):
• Myelination – process that forms myelin sheath from PM of neuroglial cells; wrap themselves
around axon forming multiple layers of membrane (myelin)
 Electric current – generated by movement of ions in body fluids
 Lipid content of myelin sheath insulates axon (prevents ion movements) like rubber
around copper wire; increases speed of action potential conduction
 Myelinated axons conduct action potentials about 15–20 x faster than unmyelinated axons
• Following diffs are noted btwn myelination in PNS (Schwann cells) & the CNS (oligodendrocytes):
 Neurolemma – found on outer surface of a myelinated axon in PNS; composed of
Schwann cell nucleus, organelles, and cytoplasm; not present in CNS (Fig 11.8a, b)
 # of axons myelinated- oligodendrocytes have multiple processes that provide myelination
for multiple axons in CNS. Schwann only provides myelination for one axon in PNS
 Timing of myelination – myelination begins early in fetal development in PNS & much
later in the CNS; very little myelin present in brain of newborn
• Axons in both CNS & PNS are generally longer than neuroglial cells so multiple cells must provide
a complete myelin sheath
 Internodes – segments of axon that are covered by neuroglia (schwann or oligoden.)
 Node of Ranvier – gap between adjacent neuroglia; where myelin sheath is absent
• Small axons in CNS and PNS are usually unmyelinated
• White matter – composed of bundles of myelinated axons that appear white.
• Gray matter – composed of neuron cell bodies, unmyelinated dendrites & axons that appear
gray. Receptive areas
Regeneration of Nervous Tissue:
• Regeneration or replacement of damaged tissue is nearly nonexistent in CNS and is limited in
PNS; neural tissue can regenerate only if cell body remains intact
• Regeneration steps (Fig 11.10):
 Axon and myelin sheath degenerate distal to injury, a process facilitated by
phagocytes; called Wallerian degeneration
 Growth processes form from proximal end of axon
 Schwann cells and basal lamina form a regeneration tube
 Single growth process grows into regeneration tube; directs new axon toward its target
cell
 New axon is reconnected to its target cell

Gliomas and Astrocytomas:

• Primary brain tumors – originate in brain; most are gliomas (caused by abnormally high rate
of division of glial cells)
• Predisposing conditions –exposure to ionizing radiation and certain diseases
• Most commonly affected cell is astrocyte; resulting tumor is called astrocytoma
 Range in severity from mild with good prognosis to highly aggressive with a very poor
prognosis
 Treatment – varies with tumor type, age, and health of patient; generally involves
surgical removal of mass with chemotherapy and perhaps radiation therapy

Neurons are more likely to regenerate their axons in the PNS, because Schwann cells secrete growth
factors that stimulate axonal growth. In the CNS, astrocytes form scar tissue and oligodendrocytes
inhibit axon regeneration
 A FULL understanding of all of the information in modules 11.3 & 11.4
MODULE 11.3 ELECTROPHYSIOLOGY OF NEURONS
11.2: Types of ion channels & other electrically excitable cells:

Fig 11.11 Measurement of the voltage across a PM. Fig 11.12 Generation of the resting membrane potential.

• Diffusion of an ion across PM is determined by both its concentration & electrical gradients
collectively called electrochemical gradient; an ex of Gradients Core Principle. Fig 11.13 The
electrochemical gradient for K+ ion

How Do Positive Ions Create a Negative Resting Membrane Potential (RMP)?

• Start w a neuron that has no membrane potential; 5 charges are distributed equally across PM
• Now, imagine that a K+ ion diffuses out of cytosol down [gradient] through a leak channel…

•
• 6+ positive charges are now outside PM and 4+ positive charges inside; makes overall charge inside
cytosol –1 & in ECF +1 —a membrane potential has been created
• Imagine that many thousands of K+ ions exit through leak channels; causes mV to become
progressively more negative. RMP= presence of concentration gradients & leak channels.
Changes in Resting Membrane Potential: Ion Movements (Fig 11.14):
Resting membrane potential is a voltage across the PM of any cell that is not being stimulated. It is
typically around -70 mV. (Results from the diff. in elect potential created by unequal ion distribution)
• Generated by unequal distribution of ions & their differing abilities for crossing PM
• Opening a gated channel in PM alters mV as it changes ability of ions to move across PM
 Depolarization – Na+ channels open, allowing Na+ ions to flow into cell; mV becomes
more positive.
 Repolarization – K+ ion channels open; allows K+ ions to flow out of cell; cell becomes
more (--) negative, returning to RMP.
 Hyperpolarization – cell becomes more negative than its normal RMP due to loss of K+
ions (cations) plus loss of anions such as Cl- chloride (may result from Cl- entering
cell more negative).

Q: Which of the following is NOT related to the opening of Na ion channels? Cell interior becomes more neg.
-Na rushes into neuron; Cell becomes less polarized; Cell depolarizes
Q: Which of the following is NOT related to the opening of K ion channels? K rushes into the neuron
-Cell becomes more polarized; Cell repolarizes; Interior of cell becomes more negative
Q: Which of the following is TRUE regarding membrane hyperpolarization? May result from Cl- ion influx
- K rushes into the neuron; Cell becomes less polarized than at rest; Interior of cell becomes more +.

Understand the different regions of a neuron & what that means in terms of action potentials
and graded potentials. Receptive- conductive- transmissive/secretory
Receptive region is the axon hillock or trigger zone where the graded info is summed.
Conductive region is axon w has AP w a RMP (-70mV- the difference in charge) more neg on inside..
Transmissive or secretory region is the synaptic end knob. Space btwn the pre & post is the synaptic
cleft where NTs are released. Voltage is the potential energy. Current is the kinetic energy. C=V/R.
Current is the flow of ions, Voltage is the difference in change of potential energy, Ligand-gated ion
channels in receptive end.
1. Na/K pump
2. Na leak channel (Na follows its gradient leaking into the cell)
3. K leak channels (K leaks out the cell- more leaky than Na so losing more K than Na, which gives
more neg mV).
-70mV RMP
Channels on= less negative (depolarizing)- let Na in to make it more + with Voltage-gated Na channel.
Once the voltage reaches a certain point, it turns on voltage-gated K channel and turns off Na
channel (repolarizing). If becomes more neg than RMP then hyperpolarizing.
Local Potentials: Graded, Reversible, & Decremental.
Local potentials – small local changes in potential of a neuron’s PM; serve as vital triggers for long-
distance APs. May cause 1 of 2 effects (in Fig 11.14):
 Depolarization – positive charges enter cytosol & make mV less negative (a change
from -70 to -60 mV).
 Hyperpolarization – either positive + charges exit or negative - charges enter cytosol;
makes mV more - negative (a change from -70 to -80 mV).
• Sometimes called graded potentials because vary greatly in size
A LP is a small, local change in the mV that can be either + or -. Decremental (they fade w distance) bc the
current that causes them is lost across the membrane as they spread.

Voltage gated channels are found in axolemma of neuron which is why other cells don’t have AP.

Action Potentials: All-or-none, Irreversible, & Nondecremental- so good for long-distance signaling.
Action potential – uniform, rapid depolarization & repolarization of mV
• Only generated in trigger zones (include Axolemma, axon hillock, & Initial segment of axon)
• States of voltage – gated channels allow ions to move & change mV of neuron; movement of K+
ions are responsible for repolarization:
• Voltage-gated K+ channels have 2 possible states: resting (closed) & activated (open)
 Resting state – channels are closed; no K+ ions are able to cross PM
 Activated state – channels are open; K+ ions are able to flow down [gradients]  ECF
(more neg mV- repolarization)

• Voltage-gated Na+ channels have 2 gates, activation gate & inactivation gate, with 3 states:
 Resting state – inact is open & act is closed; no Na+ are able to move
 Activated state – both act & inact gates are open when an AP is initiated; voltage
change opens activation gate
 Inactivated state – inact is closed & act gate is open; channel no longer allows Na+ ions
to move through; once AP is over, channel returns to resting state
 Voltage-gated channel: Activation Gate Inactivation Gate
Resting State Closed (+30mV) Open (-60mV)
Activated state Open Open
Inactivated state Open Closed

Absolute refractory period comes first. Na channel is in resting state in hyperpolarization.

• Neuronal AP has 3 general phases and lasts only a few milliseconds:
 Depolarization phase – mV rises toward 0 & then becomes positive briefly
 Repolarization phase – mV returns to a negative value
 Hyperpolarization phase – mV temporarily becomes more negative than RMP.

AP proceeds thru 3 phases bc of opening & closing of specific ion channels; following steps :
• 1. RMP Na+ rests (act-closed; in-open) & K+ resting (act-closed); Na/K pump maintains gradient
while leak channels are open
• 2. Local potential must be able to depolarize axon strongly enough to reach a level called
threshold (usually -55 mV) (EPSP at trigger zone)
• 3. Once threshold reached, voltage-gated Na+ channels activate (both- open) & Na+ ions flow
into axon causing depolarization (+)
 Positive Feedback loop—initial input (activation of Na+ ion channels & depolarization)
amplifies output (more Na+ ion channels are activated & axolemma depolarizes
further).*
• 4. Na ion channels inactivate (act-open; in-closed) & voltage-gated K+ ion channels activate:
+

Na+ ions stop flowing into axon & K+ begins exiting axon as repolarization begins (+30mV)
• 5. Repolarization occurs w K+ flowing out axon thru activated channels.
• 6. Na+ ion channels return to resting state (Act-closed; In-open) & repolarization continues
• 7. Axolemma may hyperpolarize to -90mV before K+ ion channels return to resting state; then
axolemma returns to RMP

Axolemma VG Na+ channel state VG K+ channel mV

1. RMP Resting Resting Na/K pump & -70
Act- Closed ; In- Open Act- Closed Leak channels

2. Threshold EPSP @ trigger zone -55

3. Depolarization Activated Na flow into cell

Both gates- Open

4. Peak AP Inactivated Activated - no Na+ flow +30

Act- Open ; In- Closed Act- Open - K+ flow out

5. Repolarization Activated - K+ flow out

Act- Open
 6. RMP Resting (back to resting) Slowly close -70
Act- Closed ; In- Open

7. Hyperpolarization Resting state Slow close -90

Act- Closed ; In- Open

*Short Answer Q: Graph this on exam & explain steps!

1. RMP- Na rests- activiation closed; inactivation open;
K closed; Na/K pump; leak channels
2. Activated Na channels depolarization at threshold of -55mV (ESPS at trigger zone)
3. Na channels activated= act opens; inactivation open. Na flows in depolarization
4. K opens at 30 and K flows out & Na channels inactive so act open; inact closed Na isn’t flowing
5. Repolarization (more neg so open channels and K flows out)
6. Na channels back to RMP- act-closed & inact- open; K+ channels slow close
7. Axolemma hyperpolarizes to -90

An AP is a good ex of which core principle? Feedback loops. The threshold value for neurons is typically -55mV
The MP at which Na ion channels CLOSE & K channels OPEN during an APs is +30 mV

Local Anesthetic Drugs:

• Local anesthetics – (like lidocaine) commonly administered agents for surgical or dental
procedures; produce temporary numbness in specific area
• Block voltage-gated Na+ channels of neurons in treated area; prohibits depolarization &
therefore APs relaying pain are not transmitted to CNS
• Nonselective; also affect Na+ channels in muscles of area; causes temporary paralysis; reason
for crooked smiles and drooling following dental work
Refractory Period:
*Refractory period – period of time, after neuron has generated an AP, when neuron cannot be
stimulated to generate another AP; can be divided into 2 phases:
• Absolute refractory period – when NO additional stimulus (no matter how strong) is able to
produce an additional AP. OCCURS 1st!!!!
 Coincides with voltage-gated Na+ channels being activated & inactivated
 Na+ channels may not be activated until they return to resting states (w Act- Closed
inactivation gates- open)
• Relative refractory period – follows immediately after absolute refractory period; only a
strong stimulus can produce an AP. DURING HYPERPOLARIZATION PHASE
 Voltage-gated Na+ channels have gone back to resting state & are able to open again!
 K+ channels are activated & membrane is repolarizing or hyperpolarizing; takes a much
larger stimulus to trigger an AP

Absolute refractory period (doesn’t matter how strong

impulse is, it’s not going to happen) before relative
refractory period, both depend on Na. define refractory
period-
During the ARP, no stimulus, no matter how strong,
can trigger another AP. This coincides with the
voltage-gated Na+ ion channels being activated or
inactivated (that is, not yet back to their resting state).

During the RRP, only a greater than normal stimulus

can trigger an AP. It occurs because some voltage-
gated K+ ion channels are still activated.

Local & Action Potentials Compared:

Graded local potentials produce variable changes in mV
APs cause a maximum depolarization to +30 mV
• All-or-none principle- an event (AP) that either happens completely or does not occur at all
  If a neuron does not depolarize to threshold then no AP will occur
 APs are not dependent on strength, frequency, or length of stimulus like LPs
• LPs are reversible; when stimulus ends neuron returns to RMP.
• APs are irreversible; once threshold is reached it cannot be stopped & will proceed to
completion (all-or-none)
• Signal distance is greater for APs vs. “local” potentials:
 Local potentials are decremental or decrease in strength over a short distance
 APs r nondecremental; signal strength does not decrease despite long distance travel
Propagation of Action Potentials:
APs must be conducted or propagated along entire length of axon to serve as a long-distance
signaling service:
• APs – self-propagating & travel in only 1 direction:
 Each AP triggers another in next section of axon, usually starting at trigger zone &
ending at axon terminals (like dominoes)
 APs travel in 1 direction as Na+ ion channels of each successive section of axon go into a
refractory period as next section depolarizes
 AP propagation down an axon is termed a nerve impulse!
• Events of Propagation – AP is propagated down axon in following sequence of events:

Action potentials Begin at the trigger zone

Are short distance signals; Spread down dendrites; Can be bidirectional
The threshold potential is best defined as the potential at which Voltage-gated sodium channels open
 Voltage-gated K channels open; Chemically gated Na channels open; Voltage-gated K channels close
Action potentials propagate Down axon from trigger zone to axon terminus
Down axon from axon terminus to cell body; Across multiple synapses btwn neurons; Across entire
surface of neuron cell body
Action potentials self-propagate because Each action potential triggers another in the next section of axon
ATP is always available to drive the AP; NT is released constantly; They are a form of - feedback
The refractory period of an action potential Prevents flow of action potential toward cell body
Allows bidirectional flow of the AP; Has no effect on direction of AP propagation; Is not a component
of every AP
Propagation of Action Potentials:
• Conduction speed – rate of propagation; influenced by both axon diameter and presence or
absence of myelination; conduction speed determines how rapidly signaling can occur within
nervous system (thicker diameter & myelinated have fastest conduction*)
 Axons with larger diameter have faster conduction speeds because larger axons have a
lower resistance to conduction (current flows through them more easily). Ex of Structure-
Function Core Principle
 Presence of absence of myelination gives rise to two types of conduction: saltatory and
continuous conduction
 Saltatory conduction – in myelinated axons where insulating properties of myelin sheath
increase efficiency and speed of signal conduction; action potentials only depolarize nodes
of Ranvier and “jump over” internodes
 Continuous conduction – in unmyelinated axons where every section of axolemma from
trigger zone to axon terminal must propagate action potential; slows conduction speed as
each successive section of axon must depolarize

How Does Myelination Insulate an Axon and Increase Its Speed of Propagation?
• Ideally, current flows directly down wire and illuminates light bulb
• Touch wire with a metal probe; most current might instead flow down probe; called short circuit:
• If wire is encased in material that is a poor conductor of electricity, current is unable to move
from copper wire to probe; prevents a short circuit
• Unmyelinated axon
 Most closely resembles wire in middle illustration; axolemma is very leaky with respect to
current, so current flows easily from axoplasm to extracellular fluid, just as current flowed
easily from copper wire to metal probe
  Current dissipates over a short distance, which could cause action potential to fail;
therefore must constantly be regenerated along length of axolemma; requires opening of
voltage-gated ion channels, which takes time, so propagation is slow
• Myelinated axon
 More closely resembles wire in final illustration myelin is a very good insulator (poor
conductor of electricity); prevents current from leaking out through axolemma
 Signal strength decreases very little as it travels through an internode; does not have to be
regenerated
 At unmyelinated node of Ranvier current starts to dissipate & AP must be regenerated
 APs appear to “leap” from node to node thru axoplasm; much faster than continuous
conduction
• Classification of Axons by Conduction Speed:
 Type A fibers – fastest conduction speeds (120 m/sec or 250 mi/h);
• largest diameter (5–20 mm) and myelinated; found in sensory & motor axons
associated with skeletal muscle & joints
 Type B fibers – slower conduction speeds (15 m/sec or 32 mi/hr);
• mostly myelinated with intermediate diameter axons (2–3 mm); found in efferent
fibers of ANS & some sensory axons
 Type C fibers – slowest conduction speeds (0.5–2 m/sec or 1–5 mi/hr);
• smallest diameter fibers (0.5–1.5 mm); unmyelinated axons include efferent fibers
of the ANS & sensory axons; transmit pain, temperature, and certain pressure
sensations
Putting It All Together: The Big Picture of Action Potentials
Multiple Sclerosis
• Multiple sclerosis (MS) – certain cells of immune system attack myelin sheaths within CNS; type
of autoimmune disorder (patient’s own immune system attacks part of body)
• Causes progressive loss of myelin sheath; in turn causes loss of current from neurons
• Symptoms – result from progressive slowing of action potential propagation; exact symptoms
depend on region of CNS affected; most exhibit changes in sensation (e.g., numbness), alterations
in behavior and cognitive abilities, and motor dysfunction, including paralysis

All of MODULE 11.4: NEURONAL SYNAPSES

Overview of Neuronal Synapses
• Neurons must communicate with other cells, including other neurons, in order to carry out
their functions—example of Cell-Cell Communication Core Principle
• Synapse – where a neuron meets its target cell (in this case another neuron) called a neuronal
synapse; can be either electrical or chemical (Figure 11.21):
• Neuronal synapses can occur btwn an axon of 1 neuron & another part of another neuron
 Axodendritic synapse – synapse btwn axon of 1 neuron & dendrite of another neuron
 Axosomatic synapse – synapse btwn axon of 1 neuron & cell body of another neuron
 Axoaxonic synapse –synapse btwn axon of 1 neuron & axon of another neuron


• Following terms are used to describe which neuron is sending and which is receiving message,
regardless of type of synapse:
 Presynaptic neuron – neuron sending message from its axon terminals
 Postsynaptic neuron – neuron receiving message from presynaptic neuron at its cell
body, axon, or dendrites

• Synaptic transmission – transfer of chemical or electrical signals between neurons at a

synapse; fundamental process for most functions of nervous system
 Allows for voluntary movement, cognition, sensation, and emotions to name a few
 An average presynaptic neuron forms synapses with about 1000 postsynaptic neurons
 Postsynaptic neuron can have 10,000 synaptic connections w diff presynaptic neurons
Electrical Synapses:
Electrical synapse occurs btwn cells that are electrically coupled via gap junctions (Fig 11.22a):
• Axolemmas of each cell in synapse are nearly touching; gap junctions align channels that form
pores that ions or other small substances can flow through
• Found in areas of brain responsible for programmed, automatic behaviors such as breathing
 • Outside brain, found in cardiac & visceral smooth m. to allow for coordinated muscle activity
• Electrical current can flow directly from axoplasm of 1 neuron to next; creates 2 unique
features of electrical synapses:
 Transmission is bidirectional – either neuron can be pre or postsynaptic depending on
which direction current is flowing btwn them
 Transmission is nearly instantaneous – only delay is time it takes presynaptic neuron
to depolarize (less than 0.1 milliseconds); much faster than chemical synapses (>1 msecs)

structure of electric signals

*Chemical Synapses: (we’re focusing more on chemical)
• Chemical Synapses (Fig 11.22, 11.23, 11.24, 11.25):
 Make up majority of synapses in nervous system
 More efficient than electrical synapses because they convert electrical signals into
chemical signals so no signal strength is lost (as is case at electrical synapses)

Electrical and Chemical Synapses Compared – three structural differences between chemical and
electrical synapses are noteworthy:
• Synaptic vesicles filled with chemical messengers (neurotransmitters) that transmit signals
from presynaptic to postsynaptic neurons are found at chemical synapses
• Synaptic cleft – small ECF-filled space; separates presynaptic & postsynaptic neurons; found in
chemical synapses; gap junctions connect neurons in electrical synapses
• Postsynaptic neuron has NT receptors; bind to NT secreted from presynaptic neuron that has
diffused across synaptic cleft.
• Synaptic delay – time gap btwn arrival of AP at axon terminal & effect on postsynaptic
membrane
• Chemical synapses are unidirectional, unlike electrical synapses, but allow for variable signal
intensities
• More NT released from presynaptic neuron leads to stronger response at postsynaptic neuron

Events at a Chemical Synapse. Neuronal synapses are more complicated than neuromuscular
junctions; there are multiple neurons secreting many different types of excitatory or inhibitory NTs:
• 1. An action potential in presynaptic neuron triggers voltage-gated Ca2+ ion channels in axon
terminal to open
• 2. Influx of Ca2+ ions causes synaptic vesicles to release NT into synaptic cleft
• 3. NTs bind to receptors on postsynaptic neuron
• 4. Ion channels open, leading to a local potential and possibly an action potential if threshold
is reached
 • Ca2+ pumped out of presynaptic neuron using ATP, so Ca2+ is higher outside than inside cell.
Voltage-gated Ca2+ channel that has gradient set up by Ca2+ pump. Ca2+ is attracted to PM of
vesicles, which fuse to PM of presynaptic neuron and NT is released.
• Get an excitatory post-synaptic potential by allowing Na+ in. Depolarized.
• Inhibitory post synaptic let Cl- in or K+ out. Hyperpolarized.

The correct order for events at a chemical synapse is:

AP arrives at axon terminus NT is released NT binds to receptors LP occurs in postsynaptic cell
Action potential arrival at the synaptic terminus causes: Opening of voltage-gated Ca channels
NT release from vesicles of the synaptic terminus results from: Influx of calcium into synaptic terminus
NT binding to receptors on the postsynaptic membrane Opens or closes ligand-gated Na channels

Chemical Synapses:
• Postsynaptic potentials – local potentials found in membranes of postsynaptic neuron (11.24):
 mV of postsynaptic neuron moves closer to threshold; caused by a small local
depolarization (Na+ or Ca2+ channels open) called an excitatory post-synaptic
potential (EPSP)
 mV of postsynaptic neuron moves farther away from threshold; caused by a small local
hyperpolarization (K+ or Cl- ion channels open) called an inhibitory post-synaptic
potential (IPSP) (more negative mV)

• Synaptic transmission may be terminated by ending effects of NT in one of 3 methods (11.25):

 Some NTs diffuse away from synaptic cleft in ECF; can be reabsorbed into a neuron or
an astrocyte
 NT can be broken down in synaptic cleft by enzymes; by-products of reaction can be
reabsorbed by presynaptic membrane for reassembly of original NT
 Some NTs are reabsorbed into presynaptic neuron by a process called reuptake
3 diff. ways of termination of synaptic transmission.*
Arthropod Venom:
• Venomous arthropods (in U.S.) include spiders & scorpions; many of their venoms affect
neuronal synapses; termed neurotoxins
 Female black widow (Latrodectus mactans) – toxin causes massive release of NT
leading to repetitive stimulation of postsynaptic neuron
 Bark scorpion – most lethal of 40 species in US; venom prevents postsynaptic Na+
channels from closing; membrane remains polarized & continues to fire AP
• Mechanisms are diff. but result is similar; both lead to overstimulation of postsynaptic neuron
• Common symptoms – muscle hyperexcitability, sweating, nausea/vom, & difficulty breathing
• Treatment and prognosis – depends on amount of venom received & availability of medical
care; severe cases usually require antivenin to block effects of toxin

Putting It All Together: The Big Picture of Chemical Synaptic Transmission

Neural Integration
• Neurons receive input, both inhibitory and excitatory, from multiple neurons, each of which
influences whether an action potential is generated
• Neural integration – process in which postsynaptic neuron integrates all incoming
information into a single effect
• Summation – phenomenon whereby all input from several postsynaptic potentials are added
together (EPSPs + IPSPs) to affect membrane potential at trigger zone
 An action potential will only be generated if threshold is reached; means that sum of
EPSPs must be enough to overcome sum of IPSPs
 If sum of IPSPs is greater than EPSPs then membrane will hyperpolarize; threshold will
not be reached and an action potential will not be generated
• 2 types of summation differ in timing of NT release & # of presynaptic neurons present:
 Temporal summation – NT is released repeatedly from axon terminal of a single pre-
synaptic neuron; each LP (EPSP) is short-lived so they must be generated quickly to
reach threshold & create AP
 Spatial summation involves simultaneous release of NTs from axon terminals of many
pre-synaptic neurons
• IPSPs are also subject to both temporal & spatial summation but have inhibitory effects; make
it less likely to reach threshold w subsequent AP generation

Concept Boost: How Summation Connects Local Potentials and Action Potentials
Link btwn LPs & APs is summation—as excitatory local potentials summate, they depolarize trigger
zone to threshold and initiate an action potential
Postsynaptic potentials Depend on which membrane ion channels open
Are always inhibitory
Always move the postsynaptic membrane toward threshold
Only involve Na channel opening and closing (not only)
EPSPs Move the postsynaptic membrane toward threshold
Are inhibitory
Result from K channels opening
Are usually large local potentials (can be local also? check)
IPSPs Are inhibitory & Could result from K channels opening
Move the postsynaptic membrane toward threshold
Result from sodium channels opening (excitatory)
 Are usually large local potentials
Termination of synaptic transmission is necessary because
a. Presynaptic neurons will run out of NT
b. Receptor fatigue will occur
c. Effect of NT is no longer needed
d. Postsynaptic response cannot be reinitiated until first response is terminated
Which of the following is NOT a method for termination of synaptic transmission?
a. Diffusion and absorption
b. Receptor fatigue
c. Reuptake into presynaptic neuron
d. Degradation in synaptic cleft
Which of the following is the correct sequence of major events during chemical synaptic transmission?
a. Postsynaptic potentials, synaptic transmission, action potential, synaptic transmission termination
b. Synaptic transmission termination, postsynaptic potentials, action potential, synaptic transmission
c. Action potential, synaptic transmission, postsynaptic potentials, synaptic transmission termination
d. Synaptic transmission, postsynaptic potentials, synaptic transmission termination, action potential

MODULE 11.5 NEUROTRANSMITTERS (NTs)

Neurotransmitters:
• Nearly all NTs undergo a similar pattern of use despite fact that there are > 100 known
substances; share similar features:
 Made in cell body or axon terminal and packaged into synaptic vesicles
 Released from axon terminals of presynaptic neurons; cross synaptic cleft; bind to
specific receptors on postsynaptic membrane
 Effects are often rapidly terminated through removal and/or degradation
-Funx depends on receptor- excitatory or inhibitory then direct or indirect or neuromodulator
then are you one of the 4 classes chemically (acetylcholine, biogenic amines, aa,
neuropeptides)!
Neurotransmitter Receptor:
• Type of receptor a NT binds to on postsynaptic membrane determines response; 2 types:
 Ionotropic receptors – receptors found as components of a ligand-gated ion channels;
directly control movement of ions into or out of neuron when they bind to NT (Fig
11.29a) (direct, immediate, short lived response)
 Metabotropic receptors – found within PM associated with a separate ion channel;
directly connected to metabolic processes that are initiated when NT binds (Fig 11.29b)
(indirect, long-lasting, wide-spread)
o G-proteins – group of intracellular enzymes associated with many
metabotropic receptors; activate a cascade of enzyme-catalyzed reactions;
ultimately form intracellular chemical messenger molecules called second
messengers (NT is “first messenger”)
o Second messengers can open or close ion channels in postsynaptic membrane
o Cyclic adenosine monophosphate (cAMP) – common second messenger
derived from ATP with multiple functions in neurons
o cAMP can bind to a group of enzymes that can add phosphate groups to ion
channels; either triggers channel to open or close

Major Neurotransmitters:
• Binding of NT to receptor leads to either an EPSP (w excitatory effects) or an IPSP (with
inhibitory effects)
• Most NTs can have both effects depending on which postsynaptic neuron receptors they bind;
single NT may have several receptor types
• Major NTs are classified into four groups based on chemical structure (Table 11.3)
Major NTs:
Acetylcholine
Biogenic Amines
Amino Acid
Neuropeptides
1. Acetylcholine (ACh) – small molecule NT widely used by nervous system
 Synthesized from choline and acetyl-CoA and packed into synaptic vesicles
o Acetylcholine + H2O Acetylcholinesterase Acetic acid + Choline
 Quickly degraded by acetylcholinesterase (AChE) an enzyme in synaptic cleft; by-products of
reaction are taken back into presynaptic neuron for recycling and reuse. - AchE turns Ach off.
 -Cholinergic synapses bind to ACh; found in neuromuscular junction, within brain and spinal cord
and within ANS
• Largely excitatory but it does exhibit some inhibitory effects in PNS
 Cholinergic receptors: (affect CNS)
o Nicotinic- always excitatory (in all postsynaptic neurons)-
o Muscarinic- can be excitatory or inhibitory (only in target tissues of PsNS)
Glands for PsNS (salivary, lacrimal)
In adrenal, sweat, and bv in skin of SNS. Skeletal Muscle for Somatic
2. Biogenic amines (monoamines); class of 5 NTs synthesized from aa’s; used thruout CNS & PNS for
many functions such as regulation of homeostasis and cognition; first 3 form catecholamine
subgroup, all of which are made from amino acid tyrosine; mostly excitatory:
• Norepinephrine (NE) (catecholamine, also known as noradrenalin)
 Found mainly in ANS where it influences HR, BP, and digestion;
 In CNS- NE regulates sleep/wake cycle, attention, and feeding behaviors
 • Epinephrine (catecholamine, also known as adrenalin) – also used in ANS; has similar
functions as NE; more widely used as a hormone by endocrine system.
 Hormone when released from adrenal medulla into blood that is stimulated by SNS to
make effects last longer.
 Adrenergic receptors:
o Alpha- usually excitatory (a-1- stimulate smooth m of b.v. in skin- constriction)
o Beta- excitatory or inhibitory (b-1 increase HR & rate of contraction; b-2 for
bronchiodilation to breath deeper)

a-1 a-2 b1 b-2

B.V. constrict dilate
Bronchi constrict relax
Heart Increase rate
and contraction • Dopamine (catecholamine) – used extensively by
Nerve Decrease Increase NE CNS; helps to coordinate movement; involved in
endings NE release
Mast cells Decr.
emotion and motivation
Histamine  Vasodilator at smooth muscle of b.v.’s
2nd IP3 DAG Decrease Increase cAMP  Increase GI motility, increase urine output,
messenger cAMP
reduces insulin production, reduces
activity of lymphocytes
 Schizophrenia – characterized by repetitive psychotic episodes (periods during which
patient is unable to appropriately test beliefs and perceptions against reality); thought
to result from excessive release of dopamine; management involves blocking
postsynaptic dopamine receptors
• Serotonin – synthesized from amino acid tryptophan;
 most serotonin produced in cells of the GI tract to regulate motility
 Most serotonin-secreting neurons are found in brainstem; axons project into multiple
areas of brain;
 Functions include mood regulation, emotions, attention, feeding behaviors, & daily
rhythms (circadian)
 Depressive disorders – marked by disturbances in mood; thought to result from
deficiency in synaptic transmission of serotonin, norepinephrine, and/or dopamine;
most widely used antidepressants are selective serotonin reuptake inhibitors (SSRIs);
block serotonin transporter (only), preventing reuptake by presynaptic neuron. Meds
usually result in GI complications.
 Histamine – synthesized from aa histidine; involved in regulation of arousal & attention; (as a
NT regulates sleep and in stomach produces HCL)
3. 3 main Amino Acid neurotransmitters:
 Glutamate – most important excitatory neurotransmitter in CNS; binds to its ionotropic
postsynaptic receptors and opens channels that allow for flow of both sodium and calcium ions;
generate EPSPs in postsynaptic neuron
o Learning cognition, memory
o Development of neurons and neuronal synapses.
o Info that determines cell survival
o Both essential and toxic
o Kept concentrated in the cell
This is why MSG is a prob
 Glycine and GABA – both major inhibitory NTs;
o induce IPSPs on postsynaptic neurons by opening Cl ion channels; hyperpolarize axolemma
 Glycine
o Receptors are Cl- ion channels located in ventral spinal cord
o Strychnine
 Gaba- basal nuclei, hypothalamus, midbrain, and hippocampius
o Opens Cl- channel
o Closely-associated receptor site will bind diazepam to increase ion channel
opening- minor tranquilizer
o Ethanol & barbituates
o Adaptation
o Need vitamin B6 to synthesize it
• Anxiety disorders – characterized by exaggerated and inappropriate fear responses;
believed to stem from abnormalities in norepinephrine, serotonin, and GABA
transmission; drugs for treatment include antidepressants, GABA activity enhancers,
and others that modulate norepinephrine transmission
4. Neuropeptides – group of neurotransmitters that have a wide variety of functions within nervous
system; must be synthesized in cell body and transported to axon
 Substance P – released from type C sensory afferents that carry information about pain
and temperature; also released by other neurons in brain, spinal cord, and gut
 Opioids – make up a group of > 20 neuropeptides that include endorphins,
enkephalins, & dynorphins, all of which elicit pain relief and are nervous system
depressants
 Neuropeptide Y – neuropeptide involved in feeding behaviors and may mediate
hunger or feeling full
Psychiatric Disorders and Treatments:
• Psychiatric disorders affect thought processes; generally treated by modifying synaptic
transmission to change how neurons communicate with each other or blocking them
• Psychopharmacology (study of drugs that affect higher brain functions) targets either action
potential generation or some aspect of neurotransmitter physiology:
 Schizophrenia –release of dopamine
 Depressive disorders –deficiency in synaptic transmission of serotonin, NE, dopamine
 Anxiety disorders - abnormalities in NE, serotonin, and GABA transmission
 Bipolar disorders – characterized by episodes of abnormal elevated mood (mania)
followed by depression; treatments involve decreasing ease of action potential
generation; generally block sodium channels in axolemma

KNOW 4 classes of NNT and excitatory inhibitory or neuromodulator then the classes
Division & function, General receptors
 MODULE 11.6 FUNCTIONAL GROUPS OF NEURONS
Neuronal Pools:
• Neuronal pools – groups of interneurons within CNS:
 Composed of neuroglial cells, dendrites, and axons in one location and cell bodies in
another location
 Type of information processed by a pool is defined by synaptic connections of pool
 Connections between pools allow for complex mental activity such as planned
movement, cognition, and personality (compare to past experiences)
 Input neurons initiate series of signals that starts activity of a pool

 sensory input zone more likely to reach threshold

Neuronal Circuits:
• Neural circuits – patterns of synaptic connection between neural pools; two basic types of
neural circuits:
 Diverging circuits begin with a single input neuron axon that branches out to make
contact with multiple postsynaptic neurons that follow same pattern (Fig 11.31a) (1
input, many outputs like skeletal muscle)
o Critical because they allow a single neuron to communicate with multiple parts
of brain and/or body
o Characteristic of those transmitting incoming sensory information sent from
spinal cord to different neuronal pools in brain for processing

o
 Converging circuits – basically opposite configuration of diverging circuits; axon
terminals from multiple input neurons converge on onto a single postsynaptic neuron
o Critical for control of skeletal muscle movement
o Allow nervous system to respond to sensory information that it collects and
processes (like the taste & smell of a sugar cookie then the memory is mom)
 • CNS has 2 mechanisms that stabilize neural circuits to prevent electrical activity from
becoming chaotic:
 First mechanism – inhibitory circuits provide a negative feedback mechanism to
control activity of other neural circuits
 Second mechanism – synaptic fatigue by which synaptic transmission becomes
progressively weaker with prolonged and intense excitation (ignore until gets weak)

Epileptic Seizures:
• Epilepsy – recurrent episodes of abnormal, disorganized electrical activity in brain (seizures)
• Seizures result from sudden bursts of excitatory electrical activity within a neuronal pool; may
be triggered by instability in membrane potential of a single neuron
• Excess excitation overwhelms inhibitory circuits that normally prevent overexcitation
• Continuous wave of excitation spreads over part of brain (partial seizure) or entire brain
(generalized seizure); no meaningful signals can be transmitted; ends due to synaptic fatigue
• Symptoms – mild sensory disturbances to loss of consciousness to characteristic jerking
movements (until
• Therapy – medications aimed at preventing seizures and allowing inhibitory circuits to
function properly
1 SA: Draw the AP graph and describe each step. Include gates, states of Na channel, RMP, how to
reach threshold.

2 SA: What happens at the epiphyseal plate? Longitudinal growth

What happens at each zone? How they line up w each portion of long bone.

Describe cells- what they look like & their function.

Epiphysis is pushed away from diaphysis.

3 SA: Longitudinal bone growth is growth in length that stops at a certain age.
Appositional bone growth is growth in width that can continue throughout lifetime.

4 SA: Both hypersecretion of GH

acromegaly- after plates close; excessive appositional growth- adulthood
gigantism- before plates close; excessive longitudinal growth- childhood

-4 classes of NT give ex of each structural class & description of main function of that NT
Acetylcholine-
Biogenic Amines-
Amino Acid-
Neuropeptides-

-Excitatory inhibitory determined by receptor

Excitatory- na in
Inhib- K out or Cl in

-Joints
Functional vs structural

Movements- which glide? Which give flexion, extension?

Histology – main component-osseous tissue

What characteristics to salts give?

Fibers give?

NO BONE FRACTION
Immature vs mature bone for primary vs secondary – not talking about ossification
Intracellular/ extracellular charge charts- don’t need to know know