Neurophysiology

Question 1

Which one of the following is NOT a component of the blood-brain barrier?
a. Capillary endothelial cells
b. Astrocytic foot processes
c. Basement membrane
d. Tight junctions
e. Microglia

Answer 1

e. Microglia

Question 2

Which one of the following regions has an
intact blood-brain barrier?
a. Subforniceal organ
b. Area postrema
c. Median eminence
d. Posterior pituitary
e. Pineal gland
f. Subcommissural organ
g. Organum vasculosum of lamina
terminalis

Answer 2

f. Subcommissural organ

The brain regions lacking a blood-brain barrier
are the circumventricular organs with neuroendocrine function. They may be sensory organs:
subforniceal organ, area postrema, and organum
vasculosum of lamina terminalis which can sense
levels of various plasma molecules and signal to
the autonomic system. Alternatively, they may
be secretory organs: median eminence of the
hypothalamus, pineal gland, posterior pituitary,
and subcommissural organ, which deliver hormones/glycoproteins into the bloodstream in
response to neural signals. Overall they form
part of feedback loops involved in body water
regulation, feeding, thirst, cardiovascular function, immune response and reproductive behavior. The dura and choroid plexus also lack a
blood-brain barrier. Generally, lipophilic/
hydrophobic substances can cross the BBB (e.g.,
O2, CO2, ethanol, caffeine, nicotine), whereas
lipophobic/hydrophilic/large molecules substances cannot.

Question 3

Which one of the following statements regarding the area postrema is LEAST accurate?
a. It is located in the dorsomedial medulla in
the caudal part of the fourth ventricle
b. Its blood supply is mostly from the anterior inferior cerebellar artery
c. It is a circumventricular organ
d. It plays a role as a chemoreceptor
trigger zone
e. It expresses 5-HT3 receptors

Answer 3

a. It is located in the dorsomedial medulla in the caudal part of the fourth ventricle

The area postrema is found in the dorsomedial
medulla oblongata and can be observed as two convex prominences bulging into the most caudal part
of the fourth ventricle. It is a V-shaped structure
diverging from an apex at the obex, and receives
blood supply from pyramidal branches of the posterior inferior cerebellar arteries which run along
its lateral edge. It is thought to be a chemoreceptor
trigger zone for vomiting and inhibition of 5-HT3
receptors here (as well as peripherally on vagal
afferents) is effective in reducing the nausea associated with cancer chemotherapy

Question 4

Which one of the following statements
regarding the production of CSF by choroid
plexus cells is LEAST accurate?
a. Requires ultrafiltration of plasma to form
extracellular fluid at basolateral membrane
b. Formation is primarily generated by net
secretion of Na+, Cl-, and HCO3- into ventricles
c. Water is actively pumped into the ventricles via Aquaporin 1 channels in the apical membrane
d. Active transport of Na+ into the ventricles
via Na+ /K+ ATPase occurs at the basolateral membrane
e. Basolateral membrane Na influx via Na+/H+ exchange and Na+/HCO3- cotransport channels.

Answer 4

c. Water is actively pumped into the ventricles via Aquaporin 1 channels in the apical membrane

CSF forms in two sequential stages. First, ultrafiltration of plasma occurs across the fenestrated capillary wall into the ECF beneath the basolateral membrane of the choroid epithelial cell. Second, choroid epithelial cells secrete fluid into the ventricle. Fluid secretion into the ventricles is mediated by an array of ion transporters unevenly positioned at the blood-facing (basolateral) or CSF-facing (apical) membranes. Many ionic species are involved in CSF production (e.g., K+ Mg2+, and Ca2+). However, fluid formation is primarily generated by net secretion of Na+
, Cl, and HCO3 into ventricles as water molecules
follow them passively down a chemical gradient
via Aquaporin1 channels in the apical membrane.
Na+ transport into CSF occurs due to active
transport via Na+ /K+ ATPase exchange pump at
the apical membrane, and is replaced by basolat eral membrane Na influx via Na+ /H+ exchange
and Na+ /HCO3 cotransport channels. Transport of Cl into CSF occurs via passive diffusion
via apical Cl selective channels (and possibly
Na+ /K+/Clcotransport), and is replaced at the
basolateral membrane in exchange for HCO3

Intracellular HCO3 is accumulated by (i) hydration of CO2 catalyzed by carbonic anhydrase and
(ii) influx via basolateral membrane Na/HCO3 cotransport, then can enter the CSF at the apical
membrane either by anion channel or Na/HCO3
cotransport. CSF has lower concentrations of K+
and amino acids than plasma does, and it contains
almost no protein.

Question 5

Which one of the following statements regarding axonal transport is LEAST accurate?
a. Large membranous organelles are transported by fast kinesin dependent anterograde transport and dynein dependent
retrograde transport
b. Cytosolic proteins are transported by fast transport
c. Occurs by retrograde transport
d. Anterograde transport is dependent upon
microtubules and the ATPase kinesin
e. Rabies virus spreads by retrograde axonal
transport

Answer 5

b. Cytosolic proteins are transported by fast transport

Nerve cells have an elaborate transport system that moves organelles and macromolecules between the cell body and the axon and its terminals. Axonal transport from the cell body toward the terminals is called anterograde; transport from the terminals toward the cell body is called retrograde. Anterograde axonal transport is classified into fast and
slow components. Fast transport, at speeds of up
to 400 mm/day, is based on the action of an
ATPase protein called kinesin which moves
macromolecule-containing vesicles and mitochondria along microtubules. Slow transport carries important structural and metabolic components from the cell body to axon terminals (e.g., cytoskeletal protein components such as actin, myosin,
tubulin, and cytosolic enzymes required for neurotransmitter synthesis in the presynaptic terminal)
but the mechanism is less clear. Retrograde axonal
transport along axonal microtubules is driven by
the protein dynein and allows the neuron/cell body
to respond to molecules taken up near the axon terminal by either pinocytosis or receptor-mediated endocytosis (e.g., growth factors). In addition, this form of transport functions in the continual recycling of components of the axon terminal (e.g., mitochondria). Retrograde transport of rabies virus allows replication in the cell body and spread to adjacent neurons.

Question 6

Which one of the following statements regarding the concentration of ions in extracellular and intracellular compartments is
LEAST accurate?
a. Extracellular sodium ion concentration is
approximately 140 mM (140 mEq/l)
b. Intracellular potassium ion concentration
is approximately 160 mmol/l (160 mEq/L)
c. Extracellular chloride ion concentration is
approximately 110 mM (110 mEq/l)
d. Intracellular calcium ion concentration is approximately 2 mM (4 mEq/l)
e. Extracellular bicarbonate ion concentration is approximately 22-26 mmol/l

Answer 6

d. Intracellular calcium ion concentration is approximately 2 mM (4 mEq/l)

Question 6

Which one of the following statements concerning the resting membrane potential is most accurate?
a. Maintenance of the resting membrane potential is an energy dependent process requiring Na/K-ATPase
b. A membrane is depolarized when there is
an increase in separation of the charge across it from baseline
c. Neurons become depolarized when the charge inside the cell becomes more negative compared to its resting state
d. Hyperpolarization of a cell membrane occurs when the outside of the cell becomes more negatively charged compared to its resting state
e. Resting potential difference across a membrane is not dependent on the separation of charged ions across it

Answer 6

a. Maintenance of the resting membrane potential is an energy dependent process requiring Na/K-ATPase

The voltage, or potential difference, across the
cell membrane (resting membrane potential) is
a result of the separation of positively and negatively charged ions across it, the balance of which
is actively maintained by ATP-dependent membrane pumps. At rest, the inside of a cell holds
more negative charge than the extracellular fluid
outside it. Membrane depolarization is said to
occur when the separation of charge across the
membrane is reduced from the resting/baseline
value (i.e., the inside of cell becomes more positively charged), whereas hyperpolarization is said
to occur if the separation of charge is increased
(i.e., the inside of the cell becomes more negatively charged than at rest). There is a tendency
for ions to passively leak in or out of the cell
against their respective electrochemical gradients, hence the requirement for continuously
active ATP-dependent membrane pumps to prevent an overall change in the resting membrane
potential. The propensity for ion flux across the
membrane passively down artificially membrane
pump produced and maintained electrochemical
gradients is exploited and forms the basis for
action potentials during which ion channels open
up to allow passive ion flux on a magnitude and
time scale at which ATP-dependent membrane
pumps cannot prevent, allowing depolarization/
hyperpolarization to act as a high fidelity way of
information transfer.

Question 6

Which one of the following statements
regarding ion channels is LEAST accurate?
a. Nicotinic AChR is a ligand-gated ion
channel
b. NMDA receptor is a ligand-gated cation
channel
c. Voltage-gated sodium channels open in
response to hyperpolarization of the cell
membrane
d. Cyclic AMP is generated by activation of
beta-adrenoceptors
e. GABA-B receptor is a ligand-gated ion channel

Answer 6

e. GABA-B receptor is a ligand-gated ion channel

Ion channels are transmembrane proteins that
permit the selective passage of ions with specific
characteristics (size and charge) down their electrochemical gradient by passive diffusion when
open. Ion channels are controlled by gates, and,
depending on the position of the gates, the channels may be open or closed. The higher the probability that the channel is open, the higher is its
conductance or permeability. The gates on ion
channels are controlled by three types of sensors:
* Voltage-gated channels have gates that
are controlled by changes in membrane
potential.
* Second messenger-gated channels have gates
that are controlled by changes in levels of
intracellular signaling molecules such as
cyclic AMP (e.g., beta-adrenoceptors,
alpha2-adrenoceptors, M2 muscarinic
AChR) or inositol 1,4,5-triphosphate (IP3;
e.g., alpha1-adrenoceptors, M1/M3 muscarinic AChR). In general, Gs/Gi G-protein
coupled receptor activation causes adenylyl
cyclase to convert ATP to cAMP, which then
activates protein kinase A to phosphorylate
downstream proteins. In contrast, Gq Gprotein coupled receptors cause activation
of phospholipase C which hydrolyzes membrane phospholipid (phosphatidylinositol
4,5-bisphosphate; PIP2) to diacyl glycerol
(DAG) andinositol 1,4,5-trisphosphate (IP3).
* Ligand-gated channels have gates that are
controlled by hormones and neurotransmitters. The sensors for these gates are
located on the extra-cellular side of the
ion channel (e.g., nicotinic AChR allows
Na+ and K+ passage on binding
acetylcholine).

Question 7

Which one of the following statements
regarding the membrane potentials is most
accurate?
a. The Nernst equation can be used to calculate the resting membrane potential of
a cell
b. The Goldman equation can be used to
calculate the intracellular concentration
of sodium
c. The equilibrium potential for potassium
is approximately +70 mV
d. Equilibrium potential of an ion maintains
a unique ion gradient for it exists across a
cell membrane
e. At electrochemical equilibrium, the
chemical and electrical driving forces acting on an ion are equal and opposite, and
no further net diffusion occurs

Answer 7

e. At electrochemical equilibrium, the
chemical and electrical driving forces acting on an ion are equal and opposite, and
no further net diffusion occurs

The concept of equilibrium potential is simply an
extension of the concept of diffusion potential. If
there is a concentration difference for an ion across amembrane and themembraneis permeable to that ion, a potential difference (the diffusion potential) is created. Eventually, net diffusion of the ion slows and then stops because of that potential difference.
In other words, if a cation diffuses down its concentration gradient, it carries a positive charge across the membrane, which will retard and eventually stop further diffusion of the cation. Equally, if an anion diffuses down its concentration gradient, it carries a negative charge, which will retard and then stop further diffusion of the anion. The equilibrium potential is the diffusion potential that exactly balances or opposes the tendency for diffusion down
the concentration difference. At electrochemical
equilibrium, the chemical and electrical driving
forces acting on an ion are equal and opposite,
and no further net diffusion occurs. The Nernst
equation is used to calculate the equilibrium potential for an ion at a given concentration difference across a membrane, assuming that the membrane is permeable to that ion. By definition, the equilibrium potentialis calculated for oneion at a time. For a given ion X with charge z at 37 °C, the equilibrium potential (Ex)¼(-60/z) log10([intracellular concentration of X in mmol/l]/[extracellular concentration of X in mmol/l]). For example, E(Na)¼
(-60/+1) log10(10/140)¼+68.8 mV. Whereas
for E(k)¼(-60/+1) log10 (140/10)¼-87 mV.
The Goldmann equation can be used to calculate
the exact resting membrane potential based on all
the permeable ions across it, but in practice since
in neurons 80% of conductance is due to K+ (resiual is 15% due to Na+ and 5% due to Cl-), the resting membrane voltage (Vm) of approximately
-70 mV is much closer to that of the equilibrium
potential for K+

Question 8

Which one of the following best describes ions
responsible for membrane hyperpolarization?
a. Chloride and sodium
b. Chloride and potassium
c. Potassium and sodium
d. Sodium and calcium
e. Sodium only

Answer 8

b. Chloride and potassium

Assuming normal intracellular and extracellular
concentrations of ions, both potassium and chloride ions have a negative equilibrium potential hence will result in hyperpolarization of the cell
if allowed to flow down their electrochemical
gradients. Chloride influx into the cell down
its electrochemical gradient results in a gain of
negative charge, whereas efflux of potassium
reflects a loss of positive charge in the intracellular compartment to achieve this. Physiological
electrochemical gradients for both sodium and
calcium favor influx into the cell, and would
cause depolarization due to net gain of positive
charge.

Question 9

Which one of the following statements
regarding the passive membrane properties
of neurons is LEAST accurate?
a. The length constant is the distance where
the initial voltage response to current flow
decays to 1/e (or 37%) of its value
b. Smaller length constant means passive
flow of an action potential will stop at a
shorter distance along an axon
c. Length constant is greater in unmyelinated and large diameter axons
d. The time constant is a function of the
membrane’s resistance and capacitance
e. The time constant characterizes how rapidly current flow changes the membrane
potential

Answer 9

c. Length constant is greater in unmyelinated and large diameter axons

The passive flow of electrical current plays a central role in action potential propagation, synaptic
transmission, and all other forms of electrical signaling in nerve cells. For the case of a cylindrical
axon, subthreshold current injected into one part
of the axon spreads passively along the axon until the current is dissipated (decays) by leakage out
across the axon membrane. The decrement in
the current flow with distance is described by a
simple exponential function: Vx¼V0ex/λ where
Vx is the voltage response at any distance x along
the axon, V0 is the voltage change at the point
where current is injected into the axon, e is the base
of natural logarithms (2.7), and λ is the length
constant of the axon. As evident in this relationship, the length constant is the distance where
the initial voltage response (V0) decays to 1/e (or
37%) of its value. The length constant is thus a
way to characterize how far passive current flow
spreads before it leaks out of the axon, with leakier
axons having shorter length constants. The length
constant depends upon the physical properties of
the axon, in particular the relative resistances of
the plasma membrane (Rm), the intracellular axoplasm (Ri), and the extracellular medium (R0).
The relationship between these parameters is:
λ¼√(Rm/[R0+Ri]). Hence, to improve the passive
flow of current along an axon (i.e., slow the rate of
decay), the resistance of the plasma membrane
should be as high as possible (e.g., myelination)
and the resistances of the axoplasm and extracellular medium should be low. Another important
consequence of the passive properties of neurons
is that currents flowing across a membrane do
not immediately change the membrane potential.
These delays in changing the membrane potential
are due to the fact that the plasma membrane
behaves as a capacitor, storing the initial charge
that flows at the beginning and end of the current
pulse. For the case of a cell whose membrane
potential is spatially uniform, the change in the
membrane potential at any time, Vt, after beginning the current pulse can also be described by
an exponential relationship: Vt¼V1(1et/τ
)
where V1 is the steady-state value of the membrane potential change, t is the time after the current pulse begins, and τ is the membrane time
constant. The time constant is thus defined as
the time when the voltage response (Vt) rises to
1(1/e) (or 63%) of V1. After the current pulse
ends, the membrane potential change also declines
exponentially according to the relationship
Vt¼V1et/τ During this decay, the membrane
potential returns to 1/e of V1 at a time equal to t.
The time constant characterizes how rapidly
current flow changes the membrane potential.
The membrane time constant also depends on
the physical properties of the nerve cell, specifically
on the resistance (Rm) and capacitance (Cm) of the plasma membrane such that: τ¼RmCm. The values
ofRm andCm depend,in part, on the size of the neuron, with larger cells having lower resistances and
larger capacitances. In general, small nerve cells
tend to havelong time constants andlarge cells brief
time constants. Regarding achieving threshold
for action potential generation, long time constants
favor temporal summation ofEPSPs,whereas short
time constant allows coincidence detection
through spatial summation of EPSPs/IPSPs.

Question 10

Which one of the following statements
regarding the generation of the action potential is LEAST accurate?
a. It is an all-or-nothing, regenerative wave
of depolarization
b. It can propagate bidirectionally
c. Repolarization is due to inactivation of
sodium channels combined with increased
conductance in potassium channels
d. Hyperpolarization occurs due to increases
in potassium conductance lasting beyond
the point of return to resting membrane
potential
e. Repolarization is required for inactivated
sodium channels to return to the closed state

Answer 10

b. It can propagate bidirectionally

The action potential, as classically defined, is an
all-or-nothing, regenerative, directionally propagated, depolarizing nerve impulse. At rest, the
membrane has high K+ conductance and Vm is
near the Nernst equilibrium potential for K+
(EK). Spread of an action potential from an adjacent area of the membrane brings the membrane
potential Em, to a threshold potential (approximately 40 to 55 mV) causing a large increase
in Na+ conductance of the membrane and Na+
influx such that Vm approaches the Nernst potential for Na+ (ENa) and the membrane depolarizes.
Depolarization causes voltage-gated sodium
channels to change from an open to an inactivated
state, preventing further rises in membrane
potential, and at the same time there is an increase
in conductance of delayed-rectifier K channels
causing K efflux and movement of Vm towards
the equilibrium potential for potassium (repolarization). This increased K+ conductance usually
lasts slightly longer than the time required to
bring the membrane potential back to its normal
resting level, hence there is an overshoot (hyperpolarization) which subsequently decays. An
absolute refractory period for action potential firing is seen when sodium channels are in their
inactivated state, but as repolarization progresses
more Na channels move from an inactivated to a
close state, and thus could be reopened in the
presence of a supratheshold stimulus (relative
refractory period). The figure below shows the
action potential (yellow), and underlying changes
in membrane conductance to sodium (purple) and
potassium (red) due to opening/inactivation of
channels.

Question 11

Which one of the following sites acts as the
trigger zone that integrates incoming signals
from other cells and initiates the action
potential?
a. Soma
b. Dendritic shaft
c. Dendritic spines
d. Axon hillock and initial segment
e. Axon trunk

Answer 11

d. Axon hillock and initial segment

Question 12

Which one of the following statements
regarding phenomena relevant to action
potential conduction is LEAST accurate?
a. Accommodation is dependent on postsyn- aptic receptor phagocytosis
b. Saltatory conduction occurs to high resis- tance to transmembrane current leak in myelinated segments of nerve
c. Absolute refractory period is due to inac- tivation of voltage-gated sodium channels
d. Relative refractory period occurs when
populations of inactivated voltage-gated
sodium channels return to the closed state
e. Unidirectional propagation is function of the refractory periods associated with
action potentials

Answer 12

a. Accommodation is dependent on postsyn-
aptic receptor phagocytosis

Unidirectional propagation is due to the inactive
state of the sodium channel, and this wave of
inactivation immediately following the action
potential prevents it from reversing direction.
Accommodation occurs when subthreshold stimulus will stimulate channels to open, but at a rate
that is too slow for there to be a sufficient number
of open channels at any one time to fire an AP but
sufficient for channel inactivation. Absolute
refractory period is the time period immediately
after/during the action potential upstroke when
most of the neuron’s sodium channels are inactivated and cannot be opened to elicit a second
action potential. The relative refractory period
refers to the period during repolarization when
inactivated Na channels return to a closed state
and a second action potential can be generated
but is more difficult than normal (becomes progressively less difficult to elicit an action potential
during the relative refractory period until it
returns to normal). Myelination of axons involves
wrapping the axon in myelin, which consists of
multiple layers of closely opposed glial cell membranes (i.e., oligodendrocytes in CNS, Schwann
cells in PNS). Myelination electrically insulates
the axonal membrane, reducing the ability of current to leak out of the axon and thus increasing
the distance along the axon that a given local current can flow passively such that the timeconsuming process of action potential generation
occurs only at specific points along the axon,
called nodes of Ranvier, where there is a gap in
the myelin wrapping (rather than adjacent membrane in a depolarization wave). As it happens, an
action potential generated at one node of Ranvier
elicits current that flows passively within the axoplasm of the myelinated segment until the next
node is reached and another action potential is
generated, and the cycle is repeated along the
length of the axon. Because current flows across
the neuronal membrane only at the nodes, action
potentials “leap” from node to node and this is
termed salutatory conduction. Myelination
greatly speeds up action potential conduction
(velocities up to 150 m/s) compared to unmyelinated axons (0.5-10 m/s). (In: Purves D, et al.
(Eds.), Neuroscience, 3rd ed. MA: Sinauer.)

Question 13

Which one of the following synapse types is
characterized by gap junctions?
a. Axodendritic synapses
b. Axoaxonic synapses
c. Axosomatic synapses
d. Dendrodendritic synapses
e. Electrical synapses

Answer 13

e. Electrical synapses

Electrical synapses only represent a small minority of synapses (e.g.,some neuroendocrine cells in
hypothalamus) and are characterized by very
closely apposed pre and post-synaptic membranes
connected by a gap junction. These junctions
contain aligned paired channels so that each
paired channel forms a pore (larger than those
observed in ligand-gated channels) and allows
for the bidirectional transmission. Chemical synapse types include:
Axosecretory—axon terminal secretes directly
into bloodstream (e.g., hypothalamus)
Axodendritic—axon terminal ends on dendritic spines or shaft (type I excitatory
synapse)
Axoaxonic—axon terminal secretes onto
another axon
Axoextracellular—axon with no connection
secretes into extracellular fluid
Axosomatic—axon terminal ends on cell soma
(type II inhibitory synapse, e.g., basket cell
onto Purkinje cell)
Axosynaptic—axon terminal ends on presynaptic terminal of another axon

Question 14

Which one of the following statements
regarding neurotransmission at chemical
synapses is LEAST accurate?
a. The action potential stimulates the
postsynaptic terminal to release
neurotransmitter
b. Release of the transmitter into the synaptic
cleft by exocytosis is triggered by an influx
of Ca2+ through voltage-gated channels
c. Postsynaptic current produces an excit-
atory or inhibitory postsynaptic potential
d. Neurotransmitters may undergo degrada-
tion in the synaptic cleft or be transported
back into the presynaptic terminal
e. Vesicular membrane is retrieved from the
plasma membrane after exocytosis

Answer 14

a. The action potential stimulates the postsynaptic terminal to release
neurotransmitter

Neurotransmission at a chemical synapse
requires a neurotransmitter to be synthesized
and stored in the presynaptic vesicles. The arrival
of an action potential at the presynaptic terminal
results in depolarization dependent opening of
voltage-gated Ca2+ channels and calcium influx.
Then, there is Ca2+ through these channels, causing the vesicles to fuse with the presynaptic
membrane in a mechanism mediated by synaptotagmin 1 and SNAP-25 (SNARE) calcium sensitive proteins. The transmitter is then released
into the presynaptic cleft (by exocytosis) and
binds to receptor molecules in the postsynaptic
membrane. This leads to the opening or closing
of postsynaptic channels. The resultant current
results in an EPSP or IPSP, which causes a
change in excitability of the postsynaptic cell.
The vesicular membrane is then retrieved from
the plasma membrane by endocytosis. If summation of EPSPs or IPSPs exceeds threshold potential at the axon hillock, an axon potential is
generated. To prevent repetitive stimulation,
neurotransmitters are either degraded in the presynaptic cleft or taken up by endocytosis in
presynaptic cell.

Question 15

Which one of the following statements
regarding cholinergic neurotransmission is
LEAST likely?
a. synthesized in nerve terminals from the
precursors acetyl coenzyme A
b. acetylcholinesterase (AChE) hydrolysis
Ach into acetate and choline
c. Nicotinic AChR are a nonselective cation
channel complex consisting of five subunits
arranged around a central membrane-
spanning pore
d. α-bungarotoxin binds to muscarinic AChRs
e. mAChRs are metabotropic G-protein
coupled receptors

Answer 15

d. α-bungarotoxin binds to muscarinic AChRs

In addition to the action of ACh as the neurotransmitter at skeletal neuromuscular junctions
as well as the neuromuscular synapse between
the vagus nerve and cardiac muscle fibers, ACh
serves as a transmitter at synapses in the ganglia
of the visceral motor system, and at a variety of
sites within the central nervous system. Acetylcholine is synthesized in nerve terminals from
the precursors acetyl coenzyme A (acetyl CoA,
which is synthesized from glucose) and choline,
in a reaction catalyzed by choline acetyltransferase (CAT). Choline is present in plasma at a high
concentration (about 10 mM) and is taken up into
cholinergic neurons by a high-affinity Na+
/choline transporter. After synthesis in the cytoplasm
of the neuron, a vesicular ACh transporter loads
approximately 10,000 molecules of ACh into each
cholinergic vesicle. The postsynaptic actions of
ACh at many cholinergic synapses terminated
by acetylcholinesterase (AChE) hydrolysis Ach
into acetate and choline. The choline produced
by ACh hydrolysis is transported back into nerve
terminals and used to resynthesize ACh. Many of
the postsynaptic actions of ACh are mediated by
the nicotinic ACh receptor nAChR which is a
nonselective cation channels that generate excitatory postsynaptic responses a large protein complex consisting of five subunits arranged around a
central membrane-spanning pore. In the case of
skeletal muscle AChRs, the receptor pentamer
contains two α subunits, each of which binds
one molecule of ACh. Because both ACh-binding
sites must be occupied for the channel to open,
only relatively high concentrations of this neurotransmitter lead to channel activation. These subunits also bind other ligands, such as nicotine
and α-bungarotoxin. At the neuromuscular junction, the two α subunits are combined with up to
four other types of subunit—β, γ, δ, ε—in the
ratio 2α:β:ε:δ. Neuronal nAChRs typically differ
from those of muscle in that they lack sensitivity
to α-bungarotoxin, and comprise only two receptor subunit types (α and β), which are present in a
ratio of 3α:2β. In all cases, however, five individual subunits assemble to form a functional,
cation-selective nACh receptor. Each subunit of
the nAChR molecule contains four transmembrane domains that make up the ion channel portion of the receptor, and a long extracellular
region that makes up the ACh-binding domain.
A second type of ACh receptors is activated by
muscarine and thus they are referred to as muscarinic ACh receptors (mAChRs). mAChRs are
metabotropic and mediate most of the effects of
ACh in brain via G-protein signaling. Several
subtypes of mAChR are known. Muscarinic
ACh receptors are highly expressed in the striatum and various other forebrain regions, where
they exert an inhibitory influence on dopaminemediated motor effects. These receptors are also
found in the ganglia of the peripheral nervous
system and autonomic effector organs—such as
heart, smooth muscle, and exocrine glands—
and are responsible for the inhibition of heart
rate by the vagus nerve. Nevertheless, mACh
blockers that are therapeutically useful include
atropine (used to dilate the pupil), scopolamine
(effective in preventing motion sickness), and
ipratropium (useful in the treatment of asthma)

Question 16

Which one of the following statements
regarding glutamatergic neurotransmission
is LEAST accurate?
a. At depolarized membrane potentials, an Mg2+ blocks the pore of the NMDA
receptor
b. most prevalent precursor for glutamate synthesis is glutamine
c. glutamine is taken up into presynaptic terminals and metabolized to glutamate by the mitochondrial enzyme glutaminase
d. Activation of metabotropic GluRs leads to inhibition of postsynaptic Ca2+ and Na+
channels
e. AMPA receptors are a type of metabotropic GluR

Answer 16

e. AMPA receptors are a type of metabotropic GluR

Nearly all excitatory neurons in the central nervous system are glutamatergic, and it is estimated
that over half of all brain synapses release this
agent and cause excitotocity in ischemic brain.
Glutamate is a nonessential amino acid that does
not cross the blood-brain barrier and therefore
must be synthesized in neurons from local precursors. The most prevalent precursor for glutamate synthesis is glutamine, which is released by
glial cells. Once released, glutamine is taken up
into presynaptic terminals and metabolized to
glutamate by the mitochondrial enzyme glutaminase. Glutamate can also be synthesized by
transamination of 2-oxoglutarate, an intermediate of the tricarboxylic acid cycle. Hence, some
of the glucose metabolized by neurons can also
be used for glutamate synthesis. The glutamate synthesized in the presynaptic cytoplasm is packaged into synaptic vesicles by transporters,
termed VGLUT. Once released, glutamate is
removed from the synaptic cleft by the excitatory
amino acid transporters (EAATs). Glutamate
taken up by glial cells is converted into glutamine
by the enzyme glutamine synthetase; glutamine is
then transported out of the glial cells and into
nerve terminals. In this way, synaptic terminals
cooperate with glial cells to maintain an adequate
supply of the neurotransmitter. This overall
sequence of events is referred to as the
glutamate-glutamine cycle. Receptors of these
are ionotropic receptors called, respectively,
NMDA receptors, AMPA receptors, and kainate
receptors. These glutamate receptors are named
after the agonists that activate them: NMDA
(N-methyl-D-aspartate), AMPA (α-amino-3-
hydroxyl-5-methyl-4-isoxazole-propionate), and
kainic acid. All of the ionotropic glutamate receptors are nonselective cation channels similar to
the nAChR, allowing the passage of Na+ and
K+
, and in some cases small amounts of Ca2+.
NMDA receptor ion channels allow the entry
of Ca2+ in addition to monovalent cations such
as Na+ and K+
. As a result, EPSPs produced by
NMDA receptors can increase the concentration
of Ca2+ within the postsynaptic neuron; the Ca2+
concentration change can then act as a second
messenger to activate intracellular signaling cascades. Another key property is that they bind
extracellular Mg2+. At hyperpolarized membrane
potentials, this ion blocks the pore of the NMDA
receptor channel. Depolarization, however,
pushes Mg2+ out of the pore, allowing other cations to flow. This property provides the basis for a
voltage-dependence to current flow through the
receptor and means that NMDA receptors pass
cations (most notably Ca2+) only during depolarization of the postsynaptic cell, due to either activation of a large number of excitatory inputs and/
or by repetitive firing of action potentials in the
presynaptic cell. These properties are widely
thought to be the basis for some forms of information storage at synapses, such as memory.
Another unusual property of NMRA receptors
is that opening the channel of this receptor
requires the presence of a coagonist, the amino
acid glycine. In addition to these ionotropic glutamate receptors, there are three types of metabotropic glutamate receptor (mGluRs). These
receptors, which modulate postsynaptic ion channels indirectly, differ in their coupling to intracellular signal transduction pathways and in their
sensitivity to pharmacological agents. Activation
of many of these receptors leads to inhibition of
postsynaptic Ca2+ and Na+ channels. Unlike the excitatory ionotropic glutamate receptors,
mGluRs cause slower postsynaptic responses that can either increase or decrease the excitability of postsynaptic cells.

Question 17

Which one of the following enzymatic con-
version pathways is LEAST accurate?
a. Tyrosine-tyrosine hydroxylase-DOPA
(dihydroxyphenylalanine)
b. DOPA-catechol O-methyltransferase-
dopamine
c. Histidine-histidine decarboxylase-
Histamine
d. Dopamine-Dopamine beta-hydroxylase-
Norepinephrine
e. Tryptophan is converted to serotonin
by tryptophan 5-hydroxylase and a
decarboxylase

Answer 17

b. DOPA-catechol O-methyltransferase-
dopamine

There are five well-established biogenic amine
neurotransmitters: the three catecholamines—
dopamine, norepinephrine (noradrenaline), and
epinephrine (adrenaline)—and histamine and
serotonin. Their synthesis is as follows:
* Tyrosine-tyrosine hydroxylase-DOPA
(dihydroxyphenylalanine)
* DOPA-DOPA decarboxylase-dopamine
* Dopamine-Dopamine beta-hydroxylaseNorepinephrine
* Norepinephrine-Phenylethanolamine Nmethyltransferase-Epinephrine
* Histidine-histidine decarboxylase-Histamine
* Tryptophan-tryptophan 5-hydroxylase5-hydroxytryptophan-Aromatic L-amino
acid decarboxylase-Serotonin (5-Hydroxy
tryptamine)

Question 18

Which one of the following statements
regarding dopaminergic neurotransmission
is LEAST accurate?
a. Dopamine is loaded into synaptic vesicles via a vesicular monoamine transporter (VMAT)
b. The neostriatum is the major site of dopa-minergic transmission in the brain
c. Dopamine is derived from norepinephrine
d. Cocaine inhibits the Na-dependent dopamine transporter
e. monoamine oxidase (MAO) and catechol
O-methyltransferase (COMT)

Answer 18

c. Dopamine is derived from norepinephrine

Dopamine is present in several brain regions,
although the major dopamine-containing area
of the brain is the corpus striatum, which receives
major input from the substantia nigra and plays an
essential role in the coordination of body movements. Dopamine is also believed to be involved
in motivation, reward, and reinforcement, and
many drugs of abuse work by affecting dopaminergic synapses in the CNS. In addition to these
roles in the CNS, dopamine also plays a poorly
understood role in some sympathetic ganglia.
Dopamine is produced by the action of DOPA
decarboxylase on DOPA. Following its synthesis
in the cytoplasm of presynaptic terminals, dopamine is loaded into synaptic vesicles via a vesicular
monoamine transporter (VMAT). Dopamine
action in the synaptic cleft is terminated by reuptake of dopamine into nerve terminals or
surrounding glial cells by a Na+
-dependent dopamine transporter, termed DAT. Cocaine apparently produces its psychotropic effects by
binding to and inhibiting DAT, yielding a net
increase in dopamine release from specific brain
areas. Amphetamine, another addictive drug, also
inhibits DAT as well as the transporter for
norepinephrine (see below). The two major
enzymes involved in the catabolism of dopamine are monoamine oxidase (MAO) and catechol
O-methyltransferase (COMT). Both neurons
and glia contain mitochondrial MAO and cytoplasmic COMT. Inhibitors of these enzymes,
such as phenelzine and tranylcypromine, are used
clinically as antidepressants. Once released,
dopamine acts exclusively by activating G-protein-coupled receptors. Most dopamine receptor
subtypes act by either activating or inhibiting
adenylyl cyclase. Activation of these receptors
generally contribute to complex behaviors; for
example, administration of dopamine receptor
agonists elicits hyperactivity and repetitive, stereotyped behavior in laboratory animals. Activation of another type of dopamine receptor in the medulla inhibits vomiting. Thus, antagonists of these receptors are used as emetics to induce vomiting after poisoning or a drug overdose. Dopamine receptor antagonists can also elicit catalepsy, a state in which it is difficult to initiate voluntary motor movement, suggesting a basis for this aspect of some psychoses.

Question 19

Which one of the following statements
regarding GABAergic neurotransmission is
LEAST accurate?
a. Glutamic acid decarboxylase (GAD) conversion of glutamate to GABA
b. Vitamin B6 is important in the function of glutamic acid decarboxylase
c. The mechanism of GABA removal from the synaptic cleft is similar to that for glutamate
d. GABAA and GABAC receptors are iono tropic receptors and are Ca2+ conductors
e. GABAB receptors are metabotropic and
increase K conductance

Answer 19

d. GABAA and GABAC receptors are iono tropic receptors and are Ca2+ conductors

Most inhibitory synapses in the brain and spinal
cord use either γ-aminobutyric acid (GABA) or
glycine as neurotransmitters. It is now known
that as many as a third of the synapses in the
brain use GABA as their inhibitory neurotransmitter. GABA is most commonly found in local
circuit interneurons, although cerebellar Purkinje cells provide an example of a GABAergic
projection neuron. The predominant precursor
for GABA synthesis is glucose, which is metabolized to glutamate by the tricarboxylic acid cycle
enzymes (pyruvate and glutamine can also act as
precursors). The enzyme glutamic acid decarboxylase (GAD), which is found almost exclusively in GABAergic neurons, catalyzes the
conversion of glutamate to GABA. GAD
requires a cofactor, pyridoxal phosphate, for
activity. Because pyridoxal phosphate is derived
from vitamin B6, a B6 deficiency can lead to
diminished GABA synthesis. Once GABA is synthesized, it is transported into synaptic vesicles
via a vesicular inhibitory amino acid transporter
(VIATT). The mechanism of GABA removal is
similar to that for glutamate: Both neurons and
glia contain high-affinity transporters for GABA,
termed GATs. Most GABA is eventually converted to succinate, which is metabolized further
in the tricarboxylic acid cycle that mediates cellular ATP synthesis. The enzymes required for this degradation, GABA transaminase and succinic semialdehyde dehydrogenase, are mitochondrial enzymes. Inhibitory synapses employing
GABA as their transmitter can exhibit three
types of postsynaptic receptors, called GABAA,
GABAB, and GABAC. GABAA and GABAC
receptors are ionotropic receptors, while
GABAB receptors are metabotropic. The ionotropic GABA receptors are usually inhibitory
because their associated channels are permeable
to Cl; the flow of the negatively charged chloride ions inhibits postsynaptic cells since the
reversal potential for Cl is more negative than
the threshold for neuronal firing. Like other
ionotropic receptors, GABA receptors are pentamers assembled from a combination of five types
of subunits (αβγδρ). Benzodiazepines, such as
diazepam and chlordiazepoxide, are tranquilizing
(anxiety reducing) drugs that enhance GABAergic transmission by binding to the α and δ subunits of GABAA receptors. Metabotropic GABA
receptors (GABAB) are also widely distributed in
brain. Like the ionotropic GABAA receptors,
GABAB receptors are inhibitory. Rather than
activating Cl selective channels, however,
GABAB-mediated inhibition is due to the activation of K+ channels. A second mechanism for
GABAB-mediated inhibition is by blocking Ca2+
channels, which tends to hyperpolarize postsynaptic cells. Unlike most metabotropic receptors, GABAB receptors appear to assemble as
heterodimers of GABAB R1 and R2 subunits.

Question 20

Which one of the following areas does the superior temporal gyrus (Heschl’s gyrus)
primarily receive inputs from?
a. Centromedian thalamic nucleus
b. Medial geniculate thalamic nucleus
c. Dorsomedial thalamic nucleus
d. Anterior thalamic nucleus
e. Centromedian-parafascicular nucleus

Answer 20

b. Medial geniculate thalamic nucleus

Question 21

Which one of the following cell types
involved in vision is able to generate an action
potential?
a. Ganglion cells
b. Bipolar cells
c. Horizontal cells
d. Rods and cones
e. Amacrine cells

Answer 21

a. Ganglion cells

The output of the retina is determined by ganglion cells which can generate action potentials and give rise to optic nerve. The other cell types display graded depolarizing/hyperpolarizing
responses and amacrine cells show calcium spikes. In general, 99% of all ganglion cells are concerned with details of image formation and
receive input from rods and cones via synaptic
relays through the layers of the retina, are
involved in circadian rhythms and the pupillary
light reflex. The second type, melanopsincontaining ganglion cells, comprise less than 1% of all ganglion cells, are intrinsically sensitive to light and will generate action potentials (even without rods/cones, particularly blue light); are not concerned with image formation, and have connections to the suprachiasmatic and pretectal
nuclei maintaining circadian rhythm. This type of ganglion cell explains why those blind due to rod/cone disease (e.g., retinitis pigmentosa) may still have an intact pupillary reflex and maintain circadian rhythm.

Question 22

Which one of the following statements
regarding cones and rods is LEAST accurate?
a. In the dark, rods have a high resting membrane potential of about -70 mV
b. In the dark, both rods and cones tonically release glutamate onto synapsing bipolar cells
c. Photon absorption by rhodopsin results in reduced cyclic GMP and hyperpolarization of the rod cell
d. Photon absorption by cone opsin results in reduced cyclic GMP and hyperpolarization of the rod cell
e. Reduced glutamate secretion can cause both hyperpolarization or depolarization in bipolar cells

Answer 22

a. In the dark, rods have a high resting membrane potential of about -70 mV

Rod cells are named for the shape of their outer
segment, which is a membrane-bound cylinder
containing hundreds of tightly stacked membranous discs. In the dark, cGMP levels in the rod
outer segment are high facilitating a inward Na
and Ca current results in a relatively high resting
membrane potential for rod cells, about
40 mV, and at the rod spherule there is tonic
release of glutamate. With light, rhodopsin
absorbs photons and undergoes a conformational
change causing reduced levels of cGMP, causing
closure of sodium channels, a wave of hyperpolarization and a transient reduction in this tonic
release of glutamate. Cone outer segments also
consist of a membranous stack of constantly
decreasing diameter (from cilium to tip), giving
the cell its characteristic shape. Cone opsin
absorbs photons and undergoes a conformational
change, resulting in a hyperpolarization of the
cell membrane. This hyperpolarization propagates passively to the cone’s synaptic ending,
the cone pedicle, in the outer plexiform layer.
Like rods, cones release the neurotransmitter
glutamate tonically in the dark and respond to
light with a decrease in glutamate release. There
are three types of cones, each tuned to a different
light wavelength. L-cones (red cones) are sensitive to long wavelengths, M-cones (green cones)
to medium wavelengths, and S-cones (blue
cones) to short wavelengths. Because any pure
color represents a particular wavelength of light,
each color will be represented by a unique combination of responses in the L-, M-, and S-cones.
At the posterior pole of the eye is a yellowish
spot, the macula lutea, the center of which is a
depression called the fovea centralis Cones,
which are responsible for color vision, are the
only type of photoreceptor present in the fovea.
In contrast, rods, which are most sensitive at low
levels of illumination, are the predominant photoreceptors in the periphery of the retina. The
visual world is a composite formed from a succession of foveal images carrying form and color
information supplemented with input from the
peripheral retina carrying motion information.
Several adaptations of the fovea allow it to mediate the highest visual acuity in the retina. Neurons of the inner layer of retina are actually
displaced laterally to the side of the fovea to minimize light scattering on the way to the
receptors. In addition, within the fovea, the ratio
of photoreceptors to ganglion cells falls dramatically. Most foveal receptors synapse on only one
bipolar cell, which synapses on only one ganglion cell. Because each ganglion cell is devoted
to a very small portion of the visual field, central
vision has high resolution. In other words, the
receptive field of a foveal ganglion cell (i.e.,
the region of stimulus space that can activate
it) is small. At the periphery, the ratio of receptors to ganglion cells is high; thus, each ganglion
cell has a large receptive field. The large receptive field reduces the spatial resolution of the
peripheral portion of the retina but increases
its sensitivity because more photoreceptors collect light for a ganglion cell. Lastly, the magnitude of phototransduction amplification varies
with the prevailing levels of illumination (light
adaptation). At low levels of illumination, photoreceptors are the most sensitive to light. As levels
of illumination increase, sensitivity decreases
(due to reduction in calcium currents in the
rod outer segment), preventing the receptors
from saturating and thereby greatly extending
the range of light intensities over which they
operate.

Question 23

Which one of the following events during
visual processing is LEAST accurate?
a. The on-center bipolar depolarizes in response to reduced tonic glutamate release
b. The on-center ganglion cell will produce a burst of action potentials if a spot of light is shone on the receptive field center
c. The ganglion cell that receives its input from an off-center bipolar cell will reduce
its firing rate in response a spot of light is shone on the receptive field center
d. The receptive fields of on-center and off-center ganglion cells do not overlap
e. Glutamate released from a cone cell has differential effect in different cells with
which it synapses

Answer 23

d. The receptive fields of on-center and off-center ganglion cells do not overlap

Most of the information in visual scenes consists
of spatial variations in light intensity. Each ganglion cell responds to stimulation of a small circular patch of the retina, which defines the cell’s
receptive field. Turning on a spot of light in the
receptive field center of an on-center ganglion
cell produces a burst of action potentials. The
same stimulus applied to the receptive field center of an off-center ganglion cell reduces the rate
of discharge, and when the spot of light is turned
off, the cell responds with a burst of action
potentials. Complementary patterns of activity
are also found for on-center versus off-center
cell type when a dark spot is placed in the receptive field center. Thus, on-center cells increase
their discharge rate to luminance increments in
the receptive field center, whereas off-center
cells increase their discharge rate to luminance
decrements in the receptive field center. Onand off-center ganglion cells are present in
roughly equal numbers. Their receptive fields
have overlapping distributions, so that every
point on the retinal surface (i.e., every part of
visual space) is analyzed by several on-center
and several off-center ganglion cells. In practice,
silencing on-center ganglion cells in primates caused a deficit in their ability to detect stimuli
that were brighter than the background; however, they could still see objects that were darker
than the background. These observations imply
that information about increases or decreases
in luminance is carried separately to the brain
by the axons of these two different types of retinal ganglion cells. Having separate luminance
“channels” means that changes in light intensity,
whether increases or decreases, are always conveyed to the brain by an increased number of
action potentials. Because ganglion cells rapidly
adapt to changes in luminance, their “resting”
discharge rate in constant illumination is relatively low. Although an increase in discharge rate
above resting level serves as a reliable signal, a
decrease in firing rate from an initially low rate
of discharge might not. Thus, having luminance
changes signaled by two classes of adaptable cells
provides unambiguous information about both
luminance increments and decrements. Onand off-center ganglion cells have dendrites that
arborize in separate strata of the inner plexiform
layer, forming synapses selectively with the terminals of on- and off-center bipolar cells that
respond to luminance increases and decreases,
respectively. As mentioned previously, the principal difference between ganglion cells and bipolar cells lies in the nature of their electrical
response. Like most other cells in the retina,
bipolar cells have graded potentials rather than
action potentials. Graded depolarization of bipolar cells leads to an increase in transmitter release
(glutamate) at their synapses and consequent
depolarization of the on-center ganglion cells
that they contact via AMPA, kainite, and NMDA
receptors. The selective response of on- and offcenter bipolar cells to light increments and decrements is explained by the fact that they express
different types of glutamate receptors. Off-center
bipolar cells have ionotropic receptors (AMPA
and kainate) that cause the cells to depolarize in
response to glutamate released from photoreceptor terminals. In contrast, on-center bipolar cells
express a G-protein-coupled metabotropic glutamate receptor (mGluR6). When bound to glutamate, these receptors activate an intracellular
cascade that closes cGMP-gated Na+ channels,
reducing inward current and hyperpolarizing
the cell. Decrements in light intensity naturally
have the opposite effect on these two classes of
bipolar cells, hyperpolarizing on-center cells and
depolarizing off-center ones. Retinal ganglion
cells are relatively poor at signaling differences
in the level of diffuse illumination. Instead, they
are sensitive to differences between the level of illumination that falls on the receptive field center
and the level of illumination that falls on the surround—that is, to luminance contrast. The center
of a ganglion cell receptive field is surrounded by
a concentric region (surround) that, when stimulated, antagonizes the response to stimulation of
the receptive field center (center antagonism).
In practice this means that firing of an on-center
ganglion cell is (i) increased above baseline when
a spot of light shines on receptive field center, (ii)
at baseline when the spot of light is on the center/
surround border or outside of the receptive field
completely, and (iii) reduced below baseline when
shined on the surround alone. Off-center ganglion cells demonstrate surround antagonism.
Much of the antagonism is thought to arise via
lateral connections established by horizontal cells
and photoreceptor terminals (lateral inhibition).
Thus, the information supplied by the retina to
central visual stations for further processing does
not give equal weight to all regions of the visual
scene; rather, it emphasizes the regions where
there are differences in luminance. In addition
to making ganglion cells especially sensitive to
light-dark borders in the visual scene, centersurround mechanisms make a significant contribution to the process of light adaptation as background/ambient level of illumination is less
important than scaled differences in light intensity.

Question 24

Which one of the following statements about
olfaction is LEAST accurate?
a. Bowman glands secrete a fluid that bathes the cilia of the receptors and acts as a solvent for odorant molecules
b. Mucus-coated olfactory epithelium lines the anterodorsal parts of the nasal cavities
c. Binding of odor molecules generates action potentials in a G-protein coupled mechanism
d. Fibers of CN I synapse with the mitral cells of the olfactory bulb
e. Olfactory tract and lateral olfactory stria project to the primary olfactory cortex and amygdala

Answer 24

b. Mucus-coated olfactory epithelium lines the anterodorsal parts of the nasal cavities

Smell is detected by olfactory receptor cells,
which are situated in mucus-coated olfactory
epithelium that lines the posterodorsal parts of
the nasal cavities. Olfactory glands (Bowman
glands) secrete a fluid that bathes the cilia of
the receptors and acts as a solvent for odorant
molecules. Olfactory receptor cells (first-order
neurons) are stimulated by the binding of odor
molecules to their cilia—G protein activation
and activation of adenylyl cyclase, a rise in intracellular cAMP with causes opening of a cyclicnucleotide gated ion channel allowing influx of
Na+ and Ca2+ causing neuronal depolarization.
The axons of the olfactory receptor cells form
CN I (olfactory nerve); these project through
the cribriform plate at the base of the cranium to
synapse with the mitral cells of the olfactory bulb
in olfactory glomeruli. The map of glomerular
activation patterns within the olfactory bulb are
thought to represent the quality of the odor being detected. The mitral cells of the olfactory bulb are excitatory, second-order neurons. The output axons of the mitral cells form the olfactory tract
and lateral olfactory stria, both of which project
to the primary olfactory cortex (prefrontal cortex) and the amygdala.

Question 25

Which one of the following statements regarding taste sensation is LEAST accurate?
a. Receptors for molecules associated with sweet and bitter tastes utilize second messengers
b. Sour and salty-tasting molecules act directly upon the ion channels
c. Taste buds on the anterior two thirds of the tongue sendsignals through the lingual nerve to the chorda tympani and finally into CN VII (facial)
d. Posterior one-third of the tongue detects bitter and sour tastes and signal through glossopharyngeal and vagus nerves
e. All taste fibers synapse in the nucleus ambiguus

Answer 25

e. All taste fibers synapse in the nucleus ambiguus

Taste is detected by taste receptor cells, which are
located on specialized papillae of the taste buds
and are stimulated by taste chemicals. The cellular mechanism for transduction of taste stimuli
depends upon the stimulus. Receptors for molecules associated with sweet and bitter tastes utilize
second messengers, while those associated with
sour and salty-tasting molecules act directly upon
the ion channels. Taste buds on the anterior
two thirds of the tongue have fungiform papillae
and primarily detect sweet and salty tastes. They
send signals centrally through the lingual nerve to
the chorda tympani and finally into CN VII
(facial). Taste buds on the posterior one third of
the tongue have circumvallate papillae and foliate
papillae, which detect bitter and sour tastes. Most
of them send signals centrally through CN IX
(glossopharyngeal); however, some located in the
back of the throat and epiglottis send signals
centrally through CN X (vagus). CN VII, IX,
and X synapse with the tractus solitarius (solitary
nucleus). Second-order neurons leave the solitary
nucleus and project ipsilaterally to the ventral
posterior medial nucleus of the thalamus. Neurons
from the thalamus project to the taste cortex
located in the primary somatosensory cortex.
Taste discrimination and perception occur as a
result of the comparison of the activation pattern
of different groups of taste fibers.

Question 26

Which one of the following statements concerning neurotransmission at the neuromuscular junction is most accurate?
a. It is dependent upon the release of norepinephrine from the nerve ending
b. End plate potential amplitude can be much larger than that of excitatory or inhibitory postsynaptic potentials
c. It is an all-or-none response
d. It is not directly related to the concentration of transmitter released from the pre-
synaptic terminals
e. It is dependent on the opening of ligandgated calcium channels

Answer 26

b. End plate potential amplitude can be much larger than that of excitatory or inhibitory postsynaptic potentials

An action potential in presynaptic neuron
causes calcium influx and release of acetylcholine (ACh) from presynaptic vesicles stored in
terminal bouton. Diffusion of ACh occurs
across the synaptic cleft and it binds to postsynaptic nicotinic ACh receptors which are ligandgated ion channels selective for Na+ and K+
ions, with subsequent current flow producing
membrane depolarization (end-plate potential,
EPP). The EPP is a graded potential (rather
than an all-or-none response) with an amplitude directly related to the quantity of
neurotransmitter (ACh) released from the presynaptic terminals. The amplitude of the EPP can be much greater that of the excitatory and inhibitory postsynaptic potentials in CNS synapses. At the neuromuscular junction, ACh is enzymatically degraded by acetylcholinesterase
into acetate and choline. Choline is then taken
up by the presynaptic terminal.

Question 27

Which one of the following statements regarding peripheral nerve injury is most accurate?
a. Neuropraxia involves disruption of the
myelin sheath only with some evidence
of Wallerian degeneration
b. Recovery after neuropraxia is likely to be
incomplete
c. Neurotmesis is ideally managed with
expectant management
d. Axonotmesis shows Wallerian degeneration distal to injury
e. A dense motor and sensory deficit following a penetrating injury is due to
neuropraxia

Answer 27

d. Axonotmesis shows Wallerian degeneration distal to injury

At times, it is difficult to tell what form of injury
a patient has sustained. Certainly, if a patient
has a dense motor and sensory deficit following
a penetrating injury, it probably represents
a neurotmesis and the patient will benefit from
an exploration and nerve repair. On the other
hand, if a patient sustained blunt trauma to the
upper extremity and now has a partial sensory
and motor deficit, it is difficult to know what
form of nerve injury they have sustained. Exploration of this wound may not be indicated immediately following the injury and the wait-and-see
approach may be more appropriate. Surgical
repair may involve end-to-end neurorrhaphy
(either epineural repair or fascicular repair with
cable nerve grafts), nerve graft reconstruction
of peripheral nerve (using donor nerves), neural
conduit (e.g., if significant peripheral nerve gap)
and less frequently, end-to-side neurorrhaphy.

Question 28

Which one of the following ensures sufficient
contraction of the striated portion of intrafusal fibers to enable monitor changes in muscle length?
a. Unmyelinated C fibers
b. 1A fibers
c. Gamma motor neurons
d. Alpha motor neurons
e. General visceral efferent fibers

Answer 28

c. Gamma motor neurons

Neuromuscular spindles are stretch receptor
organs within skeletal muscles which are responsible for the regulation of muscle tone via the
spinal stretch reflex. They lie parallel to the muscle fibers, embedded in endomysium or perimysium. Each spindle contains 2-10 modified
skeletal muscle fibers called intrafusal fibers,
which are much smaller than skeletal extrafusal
fibers. The intrafusal fibers have a central nonstriated area in which their nuclei tend to be concentrated. The two types of intrafusal fibers are
nuclear bag fiber and nuclear chain fiber. Associated with the intrafusal fibers are branched
non-myelinated endings of large myelinated sensory fibers which wrap around the central nonstriated area, forming annulospiral endings.
Additionally, flower-spray endings of smaller
myelinated sensory nerves are located on the
striated portions of the intrafusal fibers. These
sensory receptors are stimulated by stretching
of the intrafusal fibers, which occurs when the
(extrafusal) muscle mass is stretched. This stimulus evokes a simple two-neuron spinal cord
reflex, causing contraction of the extrafusal muscle mass. This removes the stretch stimulus from
the spindle and equilibrium is restored (e.g.,
knee jerk reflex). The sensitivity of the neuromuscular spindle to stretch is modulated via
small gamma motor neurons controlled by the
extra-pyramidal motor system. These gamma
motor neurons innervate the striated portions
of the intrafusal fibers; contraction of the intrafusal fibers increases the stretch on the fibers and
thus the sensitivity of the receptors to stretching
of the extrafusal muscle mass. During a normal
movement, both alpha and gamma motor neurons are co-activated. If only the alpha motor
neurons were activated the muscle would contract and the central non-contractile portion of
intrafusal muscle fibers would become slack and unable to monitor changes in muscle length.
However, where descending inhibition on
gamma motor neurons is impaired (e.g., UMN
lesion), this can result in exquisitely sensitive
stretch receptors and hyperreflexia.

Question 29

Neurotoxins and other agents:
a. 3,4-Methylenedioxy-methamphetamine
b. Botulinum toxin
c. Bungarotoxin
d. Curare
e. Chlorotoxin
f. Conotoxin
g. Ethanol
h. Phencyclidine (PCP)
i. Tetraethylammonium (TEA)
j. Tetrodotoxin (TTX)

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Uncompetitive NMDA receptor antagonist
producing dissociative state
2. Works by presynaptic competitive reuptake
inhibition followed by inhibition of VMAT
and TAAR1 receptor resulting in synaptic
accumulation of monoamines.
3. Neurotoxic peptides isolated from venom
of marin cone snail.
4. Blocker of voltage-gated K+ channels and competitive inhibitor of nicotinic AChRs
5. Blocker of voltage-gated Na+ channels found in Pufferfish

Answer 29

1—h, PCP; 2—a, 3,4-methylenedioxy-methamphetamine; 3—f, Conotoxin; 4—i, Tetraethylammonium (TEA); 5—j, Tetrodotoxin (TTX)

Question 30

Neurotransmitters:
a. Acetylcholine
b. Dopamine
c. Epinephrine
d. GABA
e. Glutamate
f. Glycine
g. Histamine
h. L-DOPA
i. Met-enkephalin
j. Serotonin
k. Substance P
l. Taurine
m. Tyramine
n. VIP

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. The immediate precursor of norepinephrine
2. The immediate precursor of dopamine
3. Rate limiting step in the production of this
neurotransmitter is tryptophan hydroxylase
activity
4. Phenylethanolamine-N-methyl transferase
is required for production of this
transmitter
5. Required in addition to glutamate for
co-activation of NMDA receptor, but acts
as an inhibitory neurotransmitter via Cl
channels

Answer 30

1—b,Dopamine.The conversion of dopamine
to norepinephrine comes about by the action of
the enzyme dopamine #-hydroxylase
2—h, L-DOPA. The biosynthesis of catecholamines includes the following steps: tyrosine
is converted into L-dihydroxyphenylalanine
(L-DOPA) by tyrosine hydroxylase.
L-DOPA is then decarboxylated by a decarboxylase to form dopamine (and CO2)
3—j, Serotonin. Tryptophan is converted to
5-hydroxytryptophan by tryptophan
hydroxylase and by 5-hydroxytryptophan
decarboxylase into serotonin
4—c, Epinephrine. Norepinephrine is
converted into epinephrine by
phenylethanolamine-N-methyl transferase
5—f, Glycine

Question 31

Sensory receptors:
a. Free nerve endings
b. Golgi tendon organs
c. Meissner’s corpuscles
d. Merkel’s tactile discs
e. Nuclear bag fibers
f. Nuclear chain fibers
g. Pacinian corpuscles
h. Pain nociceptors
i. Peritrichial nerve endings
j. Ruffini’s organs

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Signal the onset of muscle stretch via A-alpha myelinated fibers
2. Two-point discriminative fine touch
3. Deep pressure and vibration sense

Answer 31

1—e, Nuclear bag fibers; 2—c, Meissner’s corpuscles; 3—g, Pacinian corpuscles

Question 32

CNS cells:
a. Astrocytes
b. Basket cells
c. Betz cells
d. Ependymal cells
e. Golgi type 2 cells
f. Granule cells
g. Martinotti cells
h. Microglia
i. Oligodendroglia
j. Purkinje cells
k. Schwann cells
l. Stellate cells

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. These cells are derived from neural crest
origin and myelinate neurons of the PNS
2. These cells arise from monocytes (hemato-
poietic precursor) and thus are the resident
macrophages of the CNS. Their function is
to protect the CNS. When the brain is
damaged or infected, they become activated and multiply quickly to perform functions such as phagocytosis and presenting antigen
3. These cells myelinate neurons within the
CNS (one cell myelinates multiple neurons).
4. These are the most abundant and largest of
the glial subtypes. Their most notable role
is the metabolism and recycling of certain
neurotransmitters (glutamate, serotonin,
and gamma-aminobutyric acid [GABA]).
They also buffer the extracellular potassium
concentration, respond to injury (gliosis),
and make up the blood-brain barrier
5. These ciliated cells line the cavities of the CNS (ventricular system) in the choroid plexus, where they are involved in the production of cerebrospinal fluid (CSF) and are part of the blood-CSF barrier

Answer 32

1—k, Schwann cells; 2—h, Microglia; 3—i,
Oligodendrocytes; 4—a, Astrocytes; 5—d,
Ependymal cells

Question 33

Cerebellum:
For each of the following descriptions, select the
most appropriate answers from the image above.
Each answer may be used once, more than once
or not at all.
1. Posterior lobe
2. Flocculus
3. Primary fissure
4. Dentate nucleus
5. Anterior inferior cerebellar artery

Answer 33

1—l, 2—o, 3—k, 4—d, 5—h

Question 34

Cerebellar cortex:
For each of the following descriptions, select the
most appropriate answers from the image above.
Each answer may be used once, more than once
or not at all.
1. Purkinje cell axon
2. Basket cell
3. Climbing fiber
4. Golgi cell
5. Parallel fiber

Answer 34

1—m, 2—d, 3—k, 4—a, 5—g

Question 35

Hypothalamic-pituitary axis:
a. ACTH
b. ADH (vasopressin)
c. Cortisol
d. Epinephrine
e. FSH/LH
f. GH
g. TSH
h. Oestradiol
i. Oxytocin
j. Prolactin
k. Testosterone
For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Uterine contractions in labor and milk ejec-
tion reflex
2. Renal water conservation
3. Excess may cause galactorrhea

Answer 35

1—i, Oxytocin; 2—b, ADH (Vasopressin); 3—j, Prolactin

Question 36

Peripheral nerve:
For each of the following descriptions, select the
most appropriate answers from the image above.
Each answer may be used once, more than once
or not at all.
1. Endoneurium
2. Perineurium
3. Mesoneurium
4. External epineurium

Answer 36

1—i, 2—f, 3—a, 4—d

Question 37

Neurotoxins and other agents:
a. 3,4-Methylenedioxy-methamphetamine
b. Botulinum toxin
c. Bungarotoxin
d. Curare
e. Chlorotoxin
f. Conotoxin
g. Ethanol
h. Phencyclidine (PCP)
i. Tetraethylammonium (TEA)
j. Tetrodotoxin (TTX)

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Uncompetitive NMDA receptor antagonist
producing dissociative state
2. Works by presynaptic competitive reuptake
inhibition followed by inhibition of VMAT
and TAAR1 receptor resulting in synaptic
accumulation of monoamines.
3. Neurotoxic peptides isolated from venom
of marin cone snail.
4. Blocker of voltage-gated K+ channels and
competitive inhibitor of nicotinic AChRs
5. Blocker of voltage-gated Na+ channels
found in Pufferfish

Answer 37

1—h, PCP; 2—a, 3,4-methylenedioxy-methamphetamine; 3—f, Conotoxin; 4—i, Tetraethylammonium (TEA); 5—j,
Tetrodotoxin (TTX)

Question 38

Neurotransmitters:
a. Acetylcholine
b. Dopamine
c. Epinephrine
d. GABA
e. Glutamate
f. Glycine
g. Histamine
h. L-DOPA
i. Met-enkephalin
j. Serotonin
k. Substance P
l. Taurine
m. Tyramine
n. VIP

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. The immediate precursor of norepinephrine
2. The immediate precursor of dopamine
3. Rate limiting step in the production of this
neurotransmitter is tryptophan hydroxylase
activity
4. Phenylethanolamine-N-methyl transferase
is required for production of this
transmitter
5. Required in addition to glutamate for
co-activation of NMDA receptor, but acts
as an inhibitory neurotransmitter via Cl
channels

Answer 38

1—b,Dopamine.The conversion of dopamine to norepinephrine comes about by the action of the enzyme dopamine #-hydroxylase
2—h, L-DOPA. The biosynthesis of catecholamines includes the following steps: tyrosine
is converted into L-dihydroxyphenylalanine
(L-DOPA) by tyrosine hydroxylase.
L-DOPA is then decarboxylated by a decarboxylase to form dopamine (and CO2)
3—j, Serotonin. Tryptophan is converted to
5-hydroxytryptophan by tryptophan
hydroxylase and by 5-hydroxytryptophan
decarboxylase into serotonin
4—c, Epinephrine. Norepinephrine is
converted into epinephrine by
phenylethanolamine-N-methyl transferase
5—f, Glycine

Question 38

48. Sensory receptors:
    a. Free nerve endings
    b. Golgi tendon organs
    c. Meissner’s corpuscles
    d. Merkel’s tactile discs
    e. Nuclear bag fibers
    f. Nuclear chain fibers
    g. Pacinian corpuscles
    h. Pain nociceptors
    i. Peritrichial nerve endings
    j. Ruffini’s organs

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Signal the onset of muscle stretch via Aalpha myelinated fibers
2. Two-point discriminative fine touch
3. Deep pressure and vibration sense

Answer 38

1—e, Nuclear bag fibers; 2—c, Meissner’s corpuscles; 3—g, Pacinian corpuscles

Question 39

CNS cells:
a. Astrocytes
b. Basket cells
c. Betz cells
d. Ependymal cells
e. Golgi type 2 cells
f. Granule cells
g. Martinotti cells
h. Microglia
i. Oligodendroglia
j. Purkinje cells
k. Schwann cells
l. Stellate cells

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. These cells are derived from neural crest
origin and myelinate neurons of the PNS
2. These cells arise from monocytes (hematopoietic precursor) and thus are the resident
macrophages of the CNS. Their function is
to protect the CNS. When the brain is
damaged or infected, they become activated and multiply quickly to perform
functions such as phagocytosis and presenting antigen
3. These cells myelinate neurons within the
CNS (one cell myelinates multiple neurons).
4. These are the most abundant and largest of
the glial subtypes. Their most notable role
is the metabolism and recycling of certain
neurotransmitters (glutamate, serotonin,
and gamma-aminobutyric acid [GABA]).
They also buffer the extracellular potassium
concentration, respond to injury (gliosis),
and make up the blood-brain barrier
5. These ciliated cells line the cavities of the
CNS (ventricular system) in the choroid
plexus, where they are involved in the production of cerebrospinal fluid (CSF) and are
part of the blood-CSF barrier

Answer 39

1—k, Schwann cells; 2—h, Microglia; 3—i,
Oligodendrocytes; 4—a, Astrocytes; 5—d,
Ependymal cells

Question 40

Cerebellum:

For each of the following descriptions, select the
most appropriate answers from the image above.
Each answer may be used once, more than once
or not at all.
1. Posterior lobe
2. Flocculus
3. Primary fissure
4. Dentate nucleus
5. Anterior inferior cerebellar artery

Answer 40

1—l, 2—o, 3—k, 4—d, 5—h

Question 41

Cerebellar cortex:
For each of the following descriptions, select the
most appropriate answers from the image above.
Each answer may be used once, more than once
or not at all.
1. Purkinje cell axon
2. Basket cell
3. Climbing fiber
4. Golgi cell
5. Parallel fiber

Answer 41

1—m, 2—d, 3—k, 4—a, 5—g

Question 42

Hypothalamic-pituitary axis:
a. ACTH
b. ADH (vasopressin)
c. Cortisol
d. Epinephrine
e. FSH/LH
f. GH
g. TSH
h. Oestradiol
i. Oxytocin
j. Prolactin
k. Testosterone

For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Uterine contractions in labor and milk ejection reflex
2. Renal water conservation
3. Excess may cause galactorrhea

Answer 42

1—i, Oxytocin; 2—b, ADH (Vasopressin); 3—j, Prolactin

Question 43

Peripheral nerve:
The internal structure of a peripheral nerve

For each of the following descriptions, select the
most appropriate answers from the image above.
Each answer may be used once, more than once
or not at all.
1. Endoneurium
2. Perineurium
3. Mesoneurium
4. External epineurium

Answer 43

1—i, 2—f, 3—a, 4—d