Section II: Cellular & Molecular Neuroscience: Electrical Signaling & Synaptic Transmission

Chapter 5: Movement of Ions Across Biological Membranes: Ion Transporters & Channels

Why is the concentration of chloride in virtually all neurons lower inside than outside?

A. All neurons have chloride transporters that reduce the intracellular concentration.

B. The hyperpolarizing phase of action potentials pushes chloride outside the cell.

C. The negative potential inside neurons causes exiting of chloride ions through leakage channels.

D. Chloride accompanies the exit of sodium in the sodium/potassium active transporter.

E. None of the above are correct.

C. The negative potential inside neurons causes exiting of chloride ions through leakage channels.

What active ion transporter in neurons is necessary for the ionic concentration differences underlying the action potential?

A. Na⁺/K⁺ ATP pump

B. Ca²⁺ pump

C. Na⁺/Ca²⁺ exchange pump

D. Cl^– transporter pump

E. Na⁺/Cl^– ATP pump

A. The Na⁺/K⁺ ATP pump is necessary for the ionic concentration differences underlying the action potential.

What other molecules beside ions are transported across neural membranes by active pumps?

A. Glucose and dextrose

B. Amino acids and neurotransmitters

C. RNA

D. Molecules with phenyl rings

E. Enzymes

B. Amino acids and neurotransmitters are transported across neural membranes by active pumps.

What voltage-gated ion channel causes the relative refractory period?

A. Na⁺

B. Cl^–

C. Ca²⁺

D. K⁺

E. Mg²⁺

D. The K⁺ ion channel causes the relative refractory period.

What does the term ligand-gated mean?

A. Opened by stretch

B. Open only transiently

C. Opened by concentration differences

D. Opened by liganic ions

E. Opened by binding a neurotransmitter.

E. Ligand-gated means opened by binding a neuro-transmitter.

Chapter 6: Resting Membrane Potential & Action Potential

The resting membrane potential is characterized by which of the following?

A. Passive fluxes of Na⁺ and K⁺ are balanced by an active pump that derives energy from enzymatic hydrolysis of adenosine triphosphate (ATP).

B. A membrane is depolarized when the differences between the charges across the membrane are increased.

C. As the inside of the cell is made more negative with respect to the outside, the cell becomes depolarized.

D. In a cell whose membrane possesses only K⁺ channels, the membrane potential cannot be determined.

E. The resting membrane potential is unrelated to the separation of the charge across the membrane.

A. The potential difference across the membrane is a result of the separation charge and is called the resting membrane potential. The potential difference across the membrane is a direct function the numbers of positive and negative charges on either side of the membrane. As the separation of charge (ie, the differences between the charges) across the membrane is reduced, the membrane is said to be depolarized. Conversely, as the difference between the charges is increased, the membrane becomes hyperpolarized. In the latter case, the inside of the cell is made more negative with respect to the outside. If a cell has only a single channel in its membrane (eg, for K⁺), the gradients for the other become irrelevant and the membrane will approach the equilibrium potential for the single ion (K⁺ in this example). There is a tendency for ions to leak down their electrochemical gradients from one side of the membrane to the other. For there to be a steady resting membrane potential, the gradients across the membrane must be held constant. Changes in ionic gradients are avoided, despite the leak, by the presence of an active Na⁺/K⁺ pump (a membrane protein) that moves Na⁺ out of the cell and at the same time brings K⁺ into the cell. Such pumping mechanism requires energy because it is working against the electrochemical gradients of the 2 ions. This energy is derived from hydrolysis of ATP.

After the occurrence of an action potential, there is a repolarization of the membrane. Which of the following is the principal explanation for this event?

A. Potassium channels have been opened.

B. Sodium channels have been opened.

C. Potassium channels have been inactivated.

D. The membrane becomes impermeable to all ions.

E. There has been a sudden influx of calcium.

A. In the late phase of the action potential, potassium channels become opened and potassium efflux produces a hyperpolarization of the membrane. During the repolarization of the membrane, sodium channels are closed (sodium inactivation). Recall that activation of sodium channels is associated with the generation of the action potential. Calcium has a strong electrochemical gradient that drives it into the cell; this coincides with the upstroke of the action potential. A number of different types of calcium-gated potassium channels have been described that are activated during the action potential. Thus, it would appear that calcium influx during the action potential could generate opposing effects. On the one hand, calcium influx carries a positive charge into the cell, which contributes to the depolarization of the membrane. On the other hand, calcium influx may help to open up more potassium channels, which contributes to an outward ionic flow of potassium that causes repolarization of the membrane.

Where in the neuron is the trigger zone that integrates incoming signals from other cells and initiates the signal that the neuron sends to another neuron or a muscle cell?

A. Cell body

B. Dendritic trunk

C. Dendritic spines

D. Axon hillock and initial segment

E. Axon trunk

D. The trigger zone for the initiation of impulses from a neuron includes a specialized region of the cell body—the axon hillock—together with the section of the axon that adjoins this region—the initial segment. Other components of the neuron, such as the dendrites and cell body, receive inputs from afferent sources but are not capable of initiating impulses at these sites. The same is true about more distal aspects of the axon over which the impulse is conducted.

The equilibrium potential for potassium, as determined by the Nernst equation, differs from the resting potential of the neuron. Which of the following best accounts for this difference?

A. An active sodium-potassium pump makes an important contribution to the regulation of the resting potential.

B. The membrane is selectively permeable only to the potassium ion.

C. The Nernst equation basically considers only the relative distribution of potassium ions across the membrane.

D. The resting potential is basically dependent upon the concentration of sodium but not potassium ions across the membrane.

E. The Nernst equation fails to account for local changes in temperature that influence the resting membrane potential.

A. Because the membrane is a leaky one, the sodium-potassium pump assists in actively transporting ions from one side of the membrane to the other. The membrane is permeable to ions other than potassium, such as sodium and chloride. This fact is taken into consideration in the Goldman equation. This equation includes the distribution of all of these other ions in its formula for determining the value of membrane potential. Accordingly, the resting membrane potential is dependent upon the concentration of these other ions as well as potassium. Although it is true that the Nernst equation considers the relative distribution of potassium ions across the membrane, this statement in itself does not explain why the equilibrium potential for potassium differs from the resting potential of the neuron. The statement that the Nernst equation does not take into account differences in temperature is false. But, again, even if that statement were true, it would not account for the differences between the equilibrium potential for potassium and the resting potential of the neuron.

To which of the following does the term all-or-none response most closely relate?

A. The resting potential

B. Increased-conductance presynaptic potentials

C. Increased-conductance postsynaptic potentials

D. The generator potential

E. The action potential

E. The action potential is characterized by an all-or-none response in which the overshoot may reach an amplitude of up to 100 mV. The mechanism involves separate ion channels for sodium and potassium. The resting potential is characterized by a relatively steady potential, usually in the region of 270 mV, but that may range from 235 to 270 mV. This potential is mainly dependent on potassium and chloride channels.

Chapter 7: Mechanisms of Synaptic Transmission

Which of the following best describes a basic property of synapses in the central nervous system (CNS)?

A. Synaptic vesicles constitute important features for transmission in both chemical and electrical synapses.

B. A postsynaptic neuron typically receives input from different presynaptic axons that are either excitatory or inhibitory, but it cannot receive inputs from both types.

C. Synaptic delay is approximately the same for both chemical and electrical synapses.

D. Neurotransmitter (NT) receptors can regulate the gating/opening of an ion channel either directly (ionotropic receptor) or indirectly (metabotropic receptor)

E. The mechanism of indirect gating of ions normally does not involve the activation of G proteins.

D. Electrical synapses do not involve neurotransmitter and thus do not require synaptic vesicles. A typical postsynaptic neuron receives thousands of inputs, with synaptic inputs from excitatory, inhibitory, and modulatory neurons. Because there is no neurotransmitter release or receptors, synaptic delay is much shorter at electrical synapses. Ionotropic receptors are neurotransmitter gated ion channels, whereas metabotropic receptors can regulate ion channels indirectly. Indirect gating of ion channels involves G proteins, which can interact with ion channels, or G proteins that produce second messengers, which control protein kinases that phosphorylate and regulate ions channels.

Which of the following events directly determines the release of NTs from the terminal of the presynaptic neuron?

A. Activation of voltage-gated Na⁺ channels and Na⁺ influx

B. Activation of voltage-gated Na⁺ channels and Na⁺ efflux

C. Activation of voltage-gated K⁺ channels and K⁺ influx

D. Activation of voltage-gated K⁺ channels and K⁺ efflux

E. Activation of voltage-gated Ca²⁺ channels and Ca²⁺ influx

E. Although voltage-gated Na⁺ and K⁺ channels are involved in the generation and conduction of the action potential (with Na⁺ influx and K⁺ efflux), which is necessary to depolarize the presynaptic membrane potential, it is the influx of Ca²⁺ through the activation of voltage-gated Ca²⁺ channels that directly activates the fusion of synaptic vesicles and neurotransmitter release by the presynaptic axon.

The level and duration of NT release are determined predominantly by which of the following?

A. The magnitude and duration of the presynaptic action potential

B. The inactivation of the presynaptic voltage-gated Na⁺, K⁺, and Ca²⁺ channels

C. The frequency and pattern of presynaptic action potentials

D. The rate of recycling and refilling of synaptic vesicles

E. The extent of synaptic delay

B. The action potential has a fairly consistent (stereotypical) magnitude and duration, which does not change. Voltage-gated Na⁺ channels inactivate, but voltage-gated K⁺ and Ca²⁺ channels do not typically inactivate. The frequency and pattern of presynaptic action potentials determine how long the voltage-gated Ca²⁺ channels will be open and thus how much presynaptic Ca²⁺ influx there is and how much neurotransmitter is released and for how long. The synaptic delay does not affect the level or extent of neurotransmitter release.

Which of the following best describes NT removal from the synaptic cleft? NTs are removed by

A. astrocytic end feet located in nearby capillaries.

B. channels that open in response to depolarization.

C. transporters or degradative enzymes.

D. endocytosis by the presynaptic plasma membrane.

E. oxidation and diffusion out of the cleft.

C. Astrocytic end feet would not have access to neurotransmitters at the synapse. There are no neurotransmitter channels. Neurotransmitter transporters transport glutamate, GABA, glycine, and monoamines and biogenic amines, whereas acetylcholine is degraded by acetylcholine esterase. Most neurotransmitters are not oxidized at the cleft (monoamine oxidases were previously thought to be present in the synapse but have now been shown to be mainly intracellular).

Following exocytosis, lipids and transmembrane proteins of the synaptic vesicles that fuse with the plasma membrane can be recycled by

A. endocytosis and trafficking to the early/synaptic endosome.

B. release into the synaptic cleft and uptake by nearby astrocytes.

C. secretory trafficking via the rough endoplasmic reticulum and Golgi complex.

D. degradation through the lysosomal pathway.

E. trafficking back to the trans-Golgi network (TGN) in the cell soma.

A. After synaptic vesicles fuse with the presynaptic membrane, they undergo endocytosis and are either refilled or traffic to the early/synaptic endosome. Vesicles are not released into the cleft; only their content, the neurotransmitter, is released. The endocytosed vesicles do not traffic to the secretory pathway. Most endocytic vesicles are not degraded by lysosomes. Endocytic vesicles do not traffic back to the cell body where the TGN (Golgi) is located.

Chapter 8: Neurotransmitter Systems I: Acetylcholine & the Amino Acids

The cell bodies for neurons that synthesize and release acetylcholine (ACh), called cholinergic neurons, are located in

A. only the brainstem and spinal cord.

B. only the autonomic nervous system.

C. only the central nervous system (CNS).

D. only the peripheral nervous system (PNS).

E. both the CNS and PNS.

E. Cholinergic neurons are located in the brainstem and spinal cord (lower somatic motor neurons and preganglionic autonomic neurons), interneurons in the brain (basal forebrain, striatum, and brainstem), and autonomic ganglia (majority of postganglionic parasympathetic neurons).

A neurologist selects a drug that has properties similar to γ-aminobutyric acid (GABA) for the treatment of temporal lobe epilepsy. This neurotransmitter (NT) serves important functions within the CNS. Which of the following accurately characterizes a basic property of this NT?

A. GABA is known to have equal inhibitory and excitatory properties in the adult CNS.

B. The associated receptor channel is permeable to Cl^- ions.

C. GABA is formed directly from serine.

D. Increased GABA is associated with the generation of seizure activity.

E. GABA is present mainly in the spinal cord.

B. GABA has predominantly inhibitory actions in the adult CNS (it has some excitatory actions in the developing brain). The GABA receptor is a ligand-gated Cl^– channel, which when open, usually leads to Cl^– influx and hyperpolarization of the membrane potential and inhibition. GABA is formed from glutamate. Decreased GABA function is associated with seizures. GABA is present in both the brain and spinal cord, whereas glycine is found mainly in the spinal cord.

A patient with a history of depression is treated with a novel compound that acts mainly upon N-methyl-D-aspartate (NMDA) receptors. Which of the following best describes a basic property associated with the NMDA receptor?

A. The NMDA receptor–associated channel is blocked by the presence of Mg²⁺ at the resting membrane potential.

B. It controls a high-conductance anion channel.

C. NMDA is selective for metabotropic receptors.

D. Insufficient amounts of glutamate, acting through NMDA receptors, may cause neuronal cell death.

E. Current flow is blocked in the presence of glutamate, leading to hyperpolarization of the postsynaptic cell.

A. The NMDA receptor is a ligand (glutamate)-gated channel, but at the resting membrane potential, it is blocked by Mg²⁺ binding inside the channel pore. The NMDA receptor is a nonselective cation channel permeable to Na⁺, K⁺, and Ca²⁺. NMDA is selective for 1 subtype of glutamate ionotropic receptor. Excess glutamate acting through NMDA receptors is thought to cause excitotoxic cell death. Glutamate opens the channels if the membrane is depolarized to remove the Mg²⁺ block, leading to Na⁺ and Ca²⁺ influx (because of the larger driving forces for Na⁺ and Ca²⁺ than for K⁺), which leads to depolarization of the postsynaptic cell.

Which of the following best describes neurons in the cerebral cortex?

A. Cortical local circuit neurons release monoamines that modulate projection neurons.

B. Cortical projection neurons are mainly GABAergic and send axons to other CNS regions.

C. Cortical neurons receive inputs from other cortical regions but not other brain areas.

D. Cortical neurons are either glutamatergic or GABAergic.

E. The majority of cortical glutamatergic neurons are local circuit neurons.

D. Although they can receive inputs from all types of neurons in the brain, the only types of neurons in the cerebral cortex are glutamatergic and GABAergic neurons. Cortical local circuit neurons are GABAergic or glutamatergic. Cortical projection neurons are mainly glutamatergic. Cortical neurons receive inputs from other cortical regions as well as the thalamus and brainstem. The majority of glutamatergic neurons are projection neurons.

Summation in neurons refers to the addition of all the

A. driving forces for all the ions.

B. action potentials.

C. inhibitory postsynaptic potentials (IPSPs) and excitatory postsynaptic potentials (EPSPs).

D. Na⁺ currents.

E. Nernst/equilibrium potentials for all the ions.

C. Summation refers to the summation of all the responses from synaptic inputs, which are the postsynaptic excitatory (EPSPs) and inhibitory (IPSPs) responses in neurons. Summation occurs everywhere in the neuron, but it is important at the axon hillock initial segment since that is the place where, if the summed depolarization is above threshold, the action potential is triggered.

Chapter 9: Neurotransmitter Systems II: Monoamines, Purines, Neuropeptides, & Unconventional Neurotransmitters

In the central nervous system (CNS), all monoamine (biogenic amine) cell bodies are found in the

A. cerebral cortex or cerebellum.

B. spinal cord or brainstem.

C. brainstem or hypothalamus.

D. hypothalamus or basal forebrain.

E. sympathetic or parasympathetic ganglia.

C. All the monoamine/biogenic amine cell bodies are located in the brainstem or hypothalamus.

Monoamine (biogenic amine) neurons project to and synapse onto neurons in

A. only the autonomic nervous system.

B. only the brainstem.

C. predominantly the basal ganglia, thalamus, and cerebellum.

D. many areas of the cerebral cortex, subcortical regions, and spinal cord.

E. mainly the brainstem, hypothalamus, and basal forebrain.

D. The monoamine/biogenic amine neurons project throughout the brain and spinal cord to many areas of the cerebral cortex, to key subcortical regions such as the basal ganglia and hippocampus, and to the spinal cord.

A patient was treated with a drug whose basic mechanism involves the activation of second messengers. Which of the following statements is correct regarding second messengers within neurons?

A. They most frequently generate a marked hypersensitization of most types of receptors.

B. They regulate gene expression that controls the levels and types of proteins synthesized.

C. They generally do not affect the opening or closing of ion channels.

D. Glutamate typically generates inhibitory effects upon metabotropic receptors.

E. They are directly involved in the gating of nonselective cation channels by N-methyl-D-aspartic acid (NMDA) receptors.

B. Second messengers often lead to desensitization of receptors. Second messengers regulate protein kinases, which can control transcription and translation and hence affect gene expression. Second messengers can directly gate ion channels and also regulate protein kinases, which can also control opening or closing of ion channels. Activation of metabotropic glutamate receptors is typically excitatory. NMDA receptors are gated by glutamate binding (although they can be indirectly affected by second messengers and protein kinases).

Which of the following best describes neuropeptides (NPs)?

A. NPs are usually released by the presynaptic terminus at the active zone.

B. NPs function by activating both ionotropic and metabotropic receptors.

C. NPs are transported into small synaptic vesicles at the presynaptic terminus.

D. NPs are released following low-frequency action potential trains in the presynaptic axon.

E. NPs are cleaved by proteases in vesicles during maturation along microtubules.

E. NPs are typically released far away from the active zone. NPs activate only metabotropic receptors. NPs are packaged into larger secretory granule or dense core vesicles, not transported into synaptic vesicles. NPs typically require high-frequency action potential trains to be released because they are located further away from the active zones where the voltage-gated Ca²⁺ channels are located. NPs are synthesized as larger precursor peptides and undergo cleavage inside vesicles and maturation; they are trafficked by fast axonal transport along microtubules to the axon terminus.

Which of the following best explains how nitric oxide differs from other “classical” neurotransmitters?

A. Nitric oxide is a gaseous transmitter.

B. Nitric oxide has both excitatory and inhibitory functions.

C. Nitric oxide release by neurons occurs predominantly in response to injury.

D. The distribution of nitric oxide is limited to the peripheral nervous system.

E. Nitric oxide is packaged into vesicles.

A. Classical neurotransmitters are small organic molecules or peptides. Nitric oxide (NO) is a free radical gas. NO is usually modulatory in its function and does not directly cause inhibitory postsynaptic potentials or excitatory postsynaptic potentials. NO is typically released by classical neurotransmitter action in neurons. NO is released by neurons in the central nervous system. As a free radical gas, NO is hydrophobic and is not packed into vesicles because it can diffuse across the lipid bilayer.

Chapter 10: Synaptic Plasticity

Which of the following statements best describes neuroplasticity?

A. Neuroplasticity takes place during development but not in the adult brain.

B. Neuroplasticity is the process that prevents the brain from becoming rewired after injury and disorders.

C. Neuroplasticity is synonymous with neurotransmission.

D. Neuroplasticity is proposed to be the mechanism whereby learning and memory take place.

E. Neuroplasticity involves modification of individual synapses but not neuronal circuits.

D. Neuroplasticity occurs in both the developing and adult brain. Neuroplasticity is the mechanism that allows the brain to become rewired after injury and disorders. Neuroplasticity is what leads to a change in neurotransmission and circuit activity. Neuroplasticity is thought to underlie all types of learning and memory. Neuroplasticity likely involves modification of individual synapses, overall neuronal activity, neuronal circuits, and even formation of new neurons (neurogenesis).

Which of the following best describes synapses?

A. Synapses form predominantly during prenatal synaptogenesis but can be weakened or strengthened postnatally.

B. Synapses occur only between axons and dendrites but involve astrocytes that regulate neurotransmitter uptake.

C. Synaptogenesis occurs robustly during the critical period, and the majority of those synapses are stable in adulthood.

D. A typical interneuron receives between 1 and 10 synapses.

E. Synapses can be modified postnatally by experience and activity.

E. Synapses form (synaptogenesis) prenatally, postnatally, and in the adult brain. Synapses can occur between a presynaptic neuron and another neuron (on the dendrite, axon, or cell body), a muscle, or a gland. Synaptogenesis occurs both prenatally and postnatally, and the critical period is when a significant amount of activity-dependent synaptic refinement occurs. Some synapses are not completely stable in adulthood. A typical interneuron receives thousands of synapses. Synapses are modified by postnatal experience and activity.

Changes in synapse number and strength in the adult brain are usually called

A. synaptogenesis.

B. synaptic plasticity.

C. synaptic transmission.

D. synaptic integration.

E. adult neurogenesis.

B. Synaptogenesis is the formation of new synapses. Synaptic plasticity refers to changes (increase or decreases) in synapse number and strength (response). Synaptic transmission usually refers to the electrical or other response at the postsynaptic target. Synaptic integration can refer to summation of excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Adult neurogenesis is the formation of new neurons in the adult.

Which of the following best describes the process of long-term potentiation (LTP) as studied in the Schafer collateral (SC CA3-CA1 neurons) in the hippocampus?

A. LTP occurs in the hippocampal Schaffer collaterals (SCs), but not in other neuronal circuits.

B. LTP expression is mainly a presynaptic effect that involves an increase in presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and glutamate release.

C. Protein kinase activity, transcription, and translation are required for LTP.

D. In LTP, regulation of gene expression involves the control of transcription factors but does not involve epigenetic mechanisms.

E. LTP requires the silencing of synapses.

C. LTP has been shown to occur in many regions of the brain (hippocampus, cerebellum, and striatum) and with several types of neuronal circuits. LTP in the SC is generally a postsynaptic effect with increased AMPA receptors, although a presynaptic increase in glutamate is observed. LTP at the SC requires Ca²⁺-dependent protein kinases, transcription of new mRNA, and translation of new proteins. LTP in the SC involves regulation of gene expression that involves transcription factors and epigenetic mechanisms. LTP at the SC involves the unsilencing of previously silent synapses.

Which of the following best describes a likely function of long-term depression (LTD) in the hippocampus?

A. LTD resets synapses following synaptic and system consolidation so the hippocampus can be used for future encoding.

B. LTD releases plasticity molecules so they can be recycled and used by other nearby synapses.

C. LTD transfers information to other subregions of the hippocampus.

D. LTD decreases synaptic transmission at synapses that receive high synaptic activity and prevent excitotoxicity.

E. LTD quickly reverses the effects of LTP so that irrelevant information is forgotten.

A. One of the main functions for hippocampal LTD may be to reverse LTP after information has been transferred to cortical circuits via consolidation so that the hippocampus can be used to encode new information. Plasticity molecules are synthesized de novo and probably do not need to be recycled. Encoded information is most likely not transferred within the hippocampus and LTD is probably not required for synaptic or systems consolidation. Once induced, LTP is fairly stable, and although activity is increased at some synapses, the potentiation is not high enough to cause excitotoxicity. LTP is stable for hours to days, and the idea is that only relevant information association produces LTP.