NUR 5461 Module 4 Quiz - Advanced Pathophysiology (2026)
William Paterson University | Concepts and Alterations of the
Neurological System Practice Questions with Correct Answers
and Explanations. - 150 Questions
Section 1: Cellular and Molecular Neurobiology (Questions 1-13)
1 A researcher is investigating the molecular basis of a rare epilepsy syndrome. She identifies a mutation in a gene
encoding a voltage-gated sodium channel that impairs fast inactivation. Which of the following
electrophysiological changes is most likely to result from this mutation?
A) Prolonged hyperpolarization following an action potential due to increased potassium efflux
B) Decreased amplitude of the action potential due to reduced sodium influx
C) Increased duration of the action potential due to persistent sodium current
D) Faster repolarization due to enhanced voltage-gated potassium channel opening
Answer: C
Rationale: Fast inactivation of voltage-gated sodium channels normally terminates the sodium current rapidly after
channel opening, contributing to repolarization. Impaired inactivation leads to a persistent sodium current that
prolongs the depolarization phase, increasing action potential duration and neuronal hyperexcitability. Options A,
B, and D describe changes that would reduce excitability or shorten the action potential, opposite to the expected
effect.
2 In a laboratory model of cerebral ischemia, neurons undergo excitotoxic death due to excessive glutamate
release. Which of the following downstream molecular events is most directly responsible for the acute neuronal
injury?
A) Activation of metabotropic glutamate receptors leading to G-protein-mediated inhibition of adenylyl cyclase
B) Overactivation of AMPA receptors causing sodium influx and cytotoxic edema
C) Excessive calcium influx through NMDA receptors triggering calpain and caspase activation
D) Desensitization of GABA-A receptors resulting in disinhibition
Answer: C
Rationale: Excitotoxicity is primarily mediated by excessive calcium entry through NMDA receptors. The calcium
overload activates proteolytic enzymes (calpains) and caspases, leading to cytoskeletal degradation and
apoptotic/necrotic cell death. While AMPA receptor activation contributes to sodium influx and edema, the
calcium-dependent pathways are more directly linked to cell death. Metabotropic receptor activation and GABA-A
desensitization are secondary modulators.
3 A pharmaceutical company is developing a drug that enhances long-term potentiation (LTP) by selectively
modulating a specific postsynaptic mechanism. Which of the following targets would most effectively promote
LTP induction?
A) Antagonist of the NR2B subunit of NMDA receptors
B) Agonist of AMPA receptors that slows deactivation kinetics
C) Inhibitor of calcineurin (protein phosphatase 2B)
D) Activator of GABA-B receptors
Answer: B
Rationale: LTP induction typically requires strong postsynaptic depolarization to relieve Mg2+ block of NMDA
,receptors. An AMPA receptor agonist that slows deactivation prolongs the excitatory postsynaptic potential,
facilitating depolarization and NMDA receptor activation. Blocking NR2B would impair LTP, inhibiting
calcineurin might enhance LTP but is less direct, and activating GABA-B would inhibit LTP.
4 A mutation in the gene encoding the presynaptic protein synaptotagmin-1 impairs its calcium-sensing ability.
Which of the following synaptic processes would be most directly affected?
A) Docking of synaptic vesicles to the active zone
B) Priming of vesicles for fusion
C) Calcium-triggered exocytosis of neurotransmitter
D) Endocytosis of synaptic vesicle membrane
Answer: C
Rationale: Synaptotagmin-1 acts as the primary calcium sensor for synchronous neurotransmitter release. It binds
calcium and promotes the fusion of synaptic vesicles with the presynaptic membrane. Impaired calcium sensing
would directly reduce calcium-triggered exocytosis. Docking and priming involve other proteins (e.g., SNAREs,
Munc13), and endocytosis is mediated by different mechanisms (e.g., clathrin, dynamin).
5 In a neuron, activation of a G-protein-coupled receptor (GPCR) that couples to Gq leads to phospholipase C
(PLC) activation. Which of the following is the most direct consequence of PLC activity on neuronal
excitability?
A) Opening of voltage-gated calcium channels via direct G-protein binding
B) Activation of protein kinase C (PKC) and release of calcium from intracellular stores
C) Inhibition of adenylyl cyclase and reduction of cAMP levels
D) Activation of cyclic nucleotide-gated channels
Answer: B
Rationale: PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and
diacylglycerol (DAG). IP3 releases calcium from endoplasmic reticulum stores, and DAG activates PKC. Both can
modulate ion channels and neuronal excitability. Option A describes direct G-protein gating (e.g., in some calcium
channels), but not via PLC. Option C is typical of Gi-coupled receptors, and D is associated with cAMP/cGMP
pathways.
6 A researcher is studying a novel neurotrophin that signals through the Trk receptor tyrosine kinase. She
observes that the neurotrophin promotes neuronal survival but not differentiation. Which downstream signaling
pathway is most likely selectively activated?
A) Ras-MAPK pathway
B) PI3K-Akt pathway
C) PLC pathway
D) JAK-STAT pathway
Answer: B
Rationale: The PI3K-Akt pathway is a major mediator of neuronal survival downstream of Trk receptors. Activation
of Akt inhibits pro-apoptotic proteins and promotes cell survival. The Ras-MAPK pathway is more strongly
associated with differentiation and neurite outgrowth. PLC activation leads to calcium signaling and PKC
activation, which can influence both survival and differentiation. JAK-STAT is typically activated by cytokines, not
neurotrophins.
7 In a model of multiple sclerosis, demyelination leads to conduction block. Which of the following molecular
adaptations in demyelinated axons would most likely restore conduction?
A) Upregulation of potassium channels in the internodal region
,B) Increased expression of sodium channels along the denuded axon
C) Downregulation of sodium-potassium ATPase activity
D) Enhanced expression of myelin basic protein by oligodendrocytes
Answer: B
Rationale: In demyelinated axons, saltatory conduction fails because action potentials cannot regenerate in regions
lacking high-density sodium channels. Upregulation of voltage-gated sodium channels along the denuded axon can
allow continuous conduction, partially restoring function. Potassium channel upregulation would increase
repolarization and hinder conduction. Downregulating Na+/K+ ATPase would impair ion gradients, and enhanced
myelin protein expression is irrelevant if demyelination is ongoing.
8 A patient with a genetic disorder has a mutation that reduces the function of the glial glutamate transporter
EAAT2. Which of the following is the most likely pathophysiological consequence?
A) Increased glutamate uptake into astrocytes, leading to astrocyte swelling
B) Elevated extracellular glutamate levels, predisposing to excitotoxicity
C) Decreased synthesis of glutamine from glutamate in neurons
D) Enhanced GABAergic transmission due to glutamate spillover
Answer: B
Rationale: EAAT2 (GLT-1) is the primary astrocytic glutamate transporter responsible for clearing synaptic
glutamate. Reduced function leads to accumulation of extracellular glutamate, which can overactivate NMDA and
AMPA receptors, causing excitotoxic neuronal injury. Option A is opposite (decreased uptake), C describes a
neuronal process (glutamine synthesis via glutamine synthetase), and D is incorrect because glutamate spillover
would enhance excitatory, not inhibitory, transmission.
9 In a study of long-term depression (LTD) at a hippocampal synapse, researchers find that LTD is blocked by a
drug that prevents the internalization of AMPA receptors. Which of the following mechanisms is most likely
responsible for LTD in this synapse?
A) Postsynaptic insertion of calcium-permeable AMPA receptors
B) Presynaptic reduction of glutamate release probability
C) Clathrin-dependent endocytosis of AMPA receptors
D) Phosphorylation of AMPA receptors by PKA
Answer: C
Rationale: LTD at many synapses involves the removal of AMPA receptors from the postsynaptic membrane via
clathrin-mediated endocytosis, reducing synaptic strength. Blocking internalization prevents LTD. Option A
(insertion of calcium-permeable AMPA receptors) is associated with some forms of plasticity but not LTD.
Presynaptic changes can contribute to some LTD forms, but the drug specifically blocking internalization points to
postsynaptic mechanisms. PKA phosphorylation typically enhances AMPA receptor function, opposite to LTD.
10 A researcher is investigating the role of microRNAs in neuronal development. She finds that a specific
microRNA (miR-X) targets the mRNA of a transcription factor that promotes dendritic arborization.
Overexpression of miR-X in cultured neurons would most likely result in which of the following?
A) Increased dendritic complexity and spine density
B) Reduced dendritic branching and simplified arborization
C) Enhanced axonal growth and pathfinding
D) No change in dendritic morphology due to redundancy
Answer: B
Rationale: MicroRNAs typically bind to target mRNAs and inhibit translation or promote degradation. If miR-X
targets a transcription factor that promotes dendritic arborization, overexpression of miR-X would reduce levels of
, that transcription factor, leading to decreased dendritic branching and simplified arborization. Option A would be
expected if the microRNA were inhibiting a negative regulator. The effect is specific to dendrites, not axons (C),
and redundancy is unlikely given the direct targeting.
11 A researcher is studying the effects of a novel compound on synaptic transmission. The compound is found to
bind to a G-protein-coupled receptor (GPCR) on the presynaptic terminal, leading to a decrease in calcium
influx through voltage-gated calcium channels. Which of the following downstream signaling mechanisms
most directly mediates this effect?
A) Activation of adenylyl cyclase and increase in cAMP
B) Activation of phospholipase C and production of IP3
C) Activation of a Gi subunit that inhibits adenylyl cyclase
D) Release of G subunits that directly bind and inhibit calcium channels
Answer: D
Rationale: G ² ³ s u b u n i t s r e l e a s e d f r o m a c t i v a t e d G
inhibit them, reducing calcium influx. Gi inhibits adenylyl cyclase, affecting cAMP levels but not directly calcium
channels. PLC/IP3 pathway modulates intracellular calcium stores, not direct channel inhibition. Increased cAMP
typically enhances calcium currents.
12 In a laboratory model of long-term potentiation (LTP), a researcher observes that a specific mutation in the
NMDA receptor's GluN2B subunit prevents the receptor from binding calmodulin. Which of the following
outcomes is most likely in these mutant neurons during high-frequency stimulation?
A) Enhanced LTP due to increased calcium influx through AMPA receptors
B) Reduced LTP due to impaired calcium/calmodulin-dependent protein kinase II (CaMKII) activation
C) Increased LTP due to prolonged NMDA receptor open time
D) No change in LTP because calmodulin is not required for LTP induction
Answer: B
Rationale: Calmodulin binding to the NMDA receptor is critical for activating CaMKII, which phosphorylates
AMPA receptors to strengthen synapses during LTP. Mutation preventing calmodulin binding impairs CaMKII
activation, reducing LTP. Enhanced calcium influx through AMPA receptors is not a direct effect. Prolonged
NMDA receptor open time would not compensate for the signaling deficit.
13 A researcher is investigating the role of the sodium-potassium ATPase (Na+/K+ pump) in maintaining the
resting membrane potential. Using a patch-clamp technique, they apply a specific inhibitor of the pump to a
neuron. Which of the following immediate changes would most likely be observed?
A) Hyperpolarization due to increased intracellular potassium concentration
B) Depolarization due to accumulation of sodium ions inside the cell
C) No change in membrane potential because the pump is electrogenic only at high firing rates
D) Increase in action potential amplitude due to reduced sodium gradient
Answer: B
Rationale: The Na+/K+ pump exports 3 Na+ and imports 2 K+, creating a net outward current. Inhibition causes
Na+ accumulation intracellularly, reducing the electrochemical gradient and leading to depolarization.
Hyperpolarization would occur with increased pump activity. The pump contributes continuously to resting
potential. Reduced sodium gradient decreases action potential amplitude, not increases.
Section 2: Neuroanatomy and Functional Organization of the Nervous System (Questions 14-26)
William Paterson University | Concepts and Alterations of the
Neurological System Practice Questions with Correct Answers
and Explanations. - 150 Questions
Section 1: Cellular and Molecular Neurobiology (Questions 1-13)
1 A researcher is investigating the molecular basis of a rare epilepsy syndrome. She identifies a mutation in a gene
encoding a voltage-gated sodium channel that impairs fast inactivation. Which of the following
electrophysiological changes is most likely to result from this mutation?
A) Prolonged hyperpolarization following an action potential due to increased potassium efflux
B) Decreased amplitude of the action potential due to reduced sodium influx
C) Increased duration of the action potential due to persistent sodium current
D) Faster repolarization due to enhanced voltage-gated potassium channel opening
Answer: C
Rationale: Fast inactivation of voltage-gated sodium channels normally terminates the sodium current rapidly after
channel opening, contributing to repolarization. Impaired inactivation leads to a persistent sodium current that
prolongs the depolarization phase, increasing action potential duration and neuronal hyperexcitability. Options A,
B, and D describe changes that would reduce excitability or shorten the action potential, opposite to the expected
effect.
2 In a laboratory model of cerebral ischemia, neurons undergo excitotoxic death due to excessive glutamate
release. Which of the following downstream molecular events is most directly responsible for the acute neuronal
injury?
A) Activation of metabotropic glutamate receptors leading to G-protein-mediated inhibition of adenylyl cyclase
B) Overactivation of AMPA receptors causing sodium influx and cytotoxic edema
C) Excessive calcium influx through NMDA receptors triggering calpain and caspase activation
D) Desensitization of GABA-A receptors resulting in disinhibition
Answer: C
Rationale: Excitotoxicity is primarily mediated by excessive calcium entry through NMDA receptors. The calcium
overload activates proteolytic enzymes (calpains) and caspases, leading to cytoskeletal degradation and
apoptotic/necrotic cell death. While AMPA receptor activation contributes to sodium influx and edema, the
calcium-dependent pathways are more directly linked to cell death. Metabotropic receptor activation and GABA-A
desensitization are secondary modulators.
3 A pharmaceutical company is developing a drug that enhances long-term potentiation (LTP) by selectively
modulating a specific postsynaptic mechanism. Which of the following targets would most effectively promote
LTP induction?
A) Antagonist of the NR2B subunit of NMDA receptors
B) Agonist of AMPA receptors that slows deactivation kinetics
C) Inhibitor of calcineurin (protein phosphatase 2B)
D) Activator of GABA-B receptors
Answer: B
Rationale: LTP induction typically requires strong postsynaptic depolarization to relieve Mg2+ block of NMDA
,receptors. An AMPA receptor agonist that slows deactivation prolongs the excitatory postsynaptic potential,
facilitating depolarization and NMDA receptor activation. Blocking NR2B would impair LTP, inhibiting
calcineurin might enhance LTP but is less direct, and activating GABA-B would inhibit LTP.
4 A mutation in the gene encoding the presynaptic protein synaptotagmin-1 impairs its calcium-sensing ability.
Which of the following synaptic processes would be most directly affected?
A) Docking of synaptic vesicles to the active zone
B) Priming of vesicles for fusion
C) Calcium-triggered exocytosis of neurotransmitter
D) Endocytosis of synaptic vesicle membrane
Answer: C
Rationale: Synaptotagmin-1 acts as the primary calcium sensor for synchronous neurotransmitter release. It binds
calcium and promotes the fusion of synaptic vesicles with the presynaptic membrane. Impaired calcium sensing
would directly reduce calcium-triggered exocytosis. Docking and priming involve other proteins (e.g., SNAREs,
Munc13), and endocytosis is mediated by different mechanisms (e.g., clathrin, dynamin).
5 In a neuron, activation of a G-protein-coupled receptor (GPCR) that couples to Gq leads to phospholipase C
(PLC) activation. Which of the following is the most direct consequence of PLC activity on neuronal
excitability?
A) Opening of voltage-gated calcium channels via direct G-protein binding
B) Activation of protein kinase C (PKC) and release of calcium from intracellular stores
C) Inhibition of adenylyl cyclase and reduction of cAMP levels
D) Activation of cyclic nucleotide-gated channels
Answer: B
Rationale: PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and
diacylglycerol (DAG). IP3 releases calcium from endoplasmic reticulum stores, and DAG activates PKC. Both can
modulate ion channels and neuronal excitability. Option A describes direct G-protein gating (e.g., in some calcium
channels), but not via PLC. Option C is typical of Gi-coupled receptors, and D is associated with cAMP/cGMP
pathways.
6 A researcher is studying a novel neurotrophin that signals through the Trk receptor tyrosine kinase. She
observes that the neurotrophin promotes neuronal survival but not differentiation. Which downstream signaling
pathway is most likely selectively activated?
A) Ras-MAPK pathway
B) PI3K-Akt pathway
C) PLC pathway
D) JAK-STAT pathway
Answer: B
Rationale: The PI3K-Akt pathway is a major mediator of neuronal survival downstream of Trk receptors. Activation
of Akt inhibits pro-apoptotic proteins and promotes cell survival. The Ras-MAPK pathway is more strongly
associated with differentiation and neurite outgrowth. PLC activation leads to calcium signaling and PKC
activation, which can influence both survival and differentiation. JAK-STAT is typically activated by cytokines, not
neurotrophins.
7 In a model of multiple sclerosis, demyelination leads to conduction block. Which of the following molecular
adaptations in demyelinated axons would most likely restore conduction?
A) Upregulation of potassium channels in the internodal region
,B) Increased expression of sodium channels along the denuded axon
C) Downregulation of sodium-potassium ATPase activity
D) Enhanced expression of myelin basic protein by oligodendrocytes
Answer: B
Rationale: In demyelinated axons, saltatory conduction fails because action potentials cannot regenerate in regions
lacking high-density sodium channels. Upregulation of voltage-gated sodium channels along the denuded axon can
allow continuous conduction, partially restoring function. Potassium channel upregulation would increase
repolarization and hinder conduction. Downregulating Na+/K+ ATPase would impair ion gradients, and enhanced
myelin protein expression is irrelevant if demyelination is ongoing.
8 A patient with a genetic disorder has a mutation that reduces the function of the glial glutamate transporter
EAAT2. Which of the following is the most likely pathophysiological consequence?
A) Increased glutamate uptake into astrocytes, leading to astrocyte swelling
B) Elevated extracellular glutamate levels, predisposing to excitotoxicity
C) Decreased synthesis of glutamine from glutamate in neurons
D) Enhanced GABAergic transmission due to glutamate spillover
Answer: B
Rationale: EAAT2 (GLT-1) is the primary astrocytic glutamate transporter responsible for clearing synaptic
glutamate. Reduced function leads to accumulation of extracellular glutamate, which can overactivate NMDA and
AMPA receptors, causing excitotoxic neuronal injury. Option A is opposite (decreased uptake), C describes a
neuronal process (glutamine synthesis via glutamine synthetase), and D is incorrect because glutamate spillover
would enhance excitatory, not inhibitory, transmission.
9 In a study of long-term depression (LTD) at a hippocampal synapse, researchers find that LTD is blocked by a
drug that prevents the internalization of AMPA receptors. Which of the following mechanisms is most likely
responsible for LTD in this synapse?
A) Postsynaptic insertion of calcium-permeable AMPA receptors
B) Presynaptic reduction of glutamate release probability
C) Clathrin-dependent endocytosis of AMPA receptors
D) Phosphorylation of AMPA receptors by PKA
Answer: C
Rationale: LTD at many synapses involves the removal of AMPA receptors from the postsynaptic membrane via
clathrin-mediated endocytosis, reducing synaptic strength. Blocking internalization prevents LTD. Option A
(insertion of calcium-permeable AMPA receptors) is associated with some forms of plasticity but not LTD.
Presynaptic changes can contribute to some LTD forms, but the drug specifically blocking internalization points to
postsynaptic mechanisms. PKA phosphorylation typically enhances AMPA receptor function, opposite to LTD.
10 A researcher is investigating the role of microRNAs in neuronal development. She finds that a specific
microRNA (miR-X) targets the mRNA of a transcription factor that promotes dendritic arborization.
Overexpression of miR-X in cultured neurons would most likely result in which of the following?
A) Increased dendritic complexity and spine density
B) Reduced dendritic branching and simplified arborization
C) Enhanced axonal growth and pathfinding
D) No change in dendritic morphology due to redundancy
Answer: B
Rationale: MicroRNAs typically bind to target mRNAs and inhibit translation or promote degradation. If miR-X
targets a transcription factor that promotes dendritic arborization, overexpression of miR-X would reduce levels of
, that transcription factor, leading to decreased dendritic branching and simplified arborization. Option A would be
expected if the microRNA were inhibiting a negative regulator. The effect is specific to dendrites, not axons (C),
and redundancy is unlikely given the direct targeting.
11 A researcher is studying the effects of a novel compound on synaptic transmission. The compound is found to
bind to a G-protein-coupled receptor (GPCR) on the presynaptic terminal, leading to a decrease in calcium
influx through voltage-gated calcium channels. Which of the following downstream signaling mechanisms
most directly mediates this effect?
A) Activation of adenylyl cyclase and increase in cAMP
B) Activation of phospholipase C and production of IP3
C) Activation of a Gi subunit that inhibits adenylyl cyclase
D) Release of G subunits that directly bind and inhibit calcium channels
Answer: D
Rationale: G ² ³ s u b u n i t s r e l e a s e d f r o m a c t i v a t e d G
inhibit them, reducing calcium influx. Gi inhibits adenylyl cyclase, affecting cAMP levels but not directly calcium
channels. PLC/IP3 pathway modulates intracellular calcium stores, not direct channel inhibition. Increased cAMP
typically enhances calcium currents.
12 In a laboratory model of long-term potentiation (LTP), a researcher observes that a specific mutation in the
NMDA receptor's GluN2B subunit prevents the receptor from binding calmodulin. Which of the following
outcomes is most likely in these mutant neurons during high-frequency stimulation?
A) Enhanced LTP due to increased calcium influx through AMPA receptors
B) Reduced LTP due to impaired calcium/calmodulin-dependent protein kinase II (CaMKII) activation
C) Increased LTP due to prolonged NMDA receptor open time
D) No change in LTP because calmodulin is not required for LTP induction
Answer: B
Rationale: Calmodulin binding to the NMDA receptor is critical for activating CaMKII, which phosphorylates
AMPA receptors to strengthen synapses during LTP. Mutation preventing calmodulin binding impairs CaMKII
activation, reducing LTP. Enhanced calcium influx through AMPA receptors is not a direct effect. Prolonged
NMDA receptor open time would not compensate for the signaling deficit.
13 A researcher is investigating the role of the sodium-potassium ATPase (Na+/K+ pump) in maintaining the
resting membrane potential. Using a patch-clamp technique, they apply a specific inhibitor of the pump to a
neuron. Which of the following immediate changes would most likely be observed?
A) Hyperpolarization due to increased intracellular potassium concentration
B) Depolarization due to accumulation of sodium ions inside the cell
C) No change in membrane potential because the pump is electrogenic only at high firing rates
D) Increase in action potential amplitude due to reduced sodium gradient
Answer: B
Rationale: The Na+/K+ pump exports 3 Na+ and imports 2 K+, creating a net outward current. Inhibition causes
Na+ accumulation intracellularly, reducing the electrochemical gradient and leading to depolarization.
Hyperpolarization would occur with increased pump activity. The pump contributes continuously to resting
potential. Reduced sodium gradient decreases action potential amplitude, not increases.
Section 2: Neuroanatomy and Functional Organization of the Nervous System (Questions 14-26)
