Researchers find that repeated stimulation of hippocampal neurons involved in memory and learning leads to potentiation of synaptic transmission. Patch-clamp recordings of stimulated neurons are shown below (dotted line: baseline; solid line: after repeated stimulation [potentiated]). Which of the following neurotransmitter receptors on the postsynaptic membrane is most likely involved in this process?

Question

Researchers find that repeated stimulation of hippocampal neurons involved in memory and learning leads to potentiation of synaptic transmission.  Patch-clamp recordings of stimulated neurons are shown below (dotted line: baseline; solid line: after repeated stimulation [potentiated]).  Which of the following neurotransmitter receptors on the postsynaptic membrane is most likely involved in this process?

Quizplus · Accepted Answer

11ec160b_3cd2_4fb3_9249_a1bcce0fabdf_MD0001_00 The top panel in this experiment demonstrates a classic excitatory postsynaptic potential (EPSP), a small depolarization that moves the postsynaptic neuron closer to the threshold for full action potential firing. The EPSP occurs with rising intracellular calcium (bottom panel), indicating that the involved postsynaptic receptor acts, at least in part, by increasing calcium conductance. The glutamate NMDA receptor becomes permeable to cations causing net depolarization (sodium and calcium in > potassium out) when bound by glutamate. The increased calcium entry also initiates second-messenger signaling cascades (eg, protein kinase C) to regulate synaptic plasticity; repetitive excitation of postsynaptic neurons renders them more responsive, producing stronger EPSPs over time. This process, known as long-term potentiation (LTP), dictates synaptic strength between hippocampal neurons and plays a critical role in the molecular basis of memory, learning, and addiction. Because of its role in memory, acute blockade of glutamate NMDA receptors confers the amnestic property of certain medications (eg, ketamine) and some drugs of illicit use (eg, phencyclidine [PCP]). However, chronic blockade (eg, memantine) can exert neuroprotective effects by dampening glutamate-induced excitotoxicity (ie, neuron apoptosis due to calcium overload). (Choice A) Dopamine can be either excitatory or inhibitory depending on the receptor subtype. D₂ receptors are generally coupled to G_i proteins that inhibit protein kinase A, leading to the opening of potassium channels that inhibit neuronal depolarization. (Choice B) GABA is the chief inhibitory neurotransmitter, causing postsynaptic hyperpolarization via increased chloride and bicarbonate influx (ie, ionotropic GABA-A ion channel) or increased potassium efflux (ie, metabotropic GABA-B receptor). (Choice D) The glycine receptor causes inhibitory postsynaptic hyperpolarization via increasing membrane permeability to chloride. This receptor mediates inhibitory interneuron transmission in the spinal cord. (Choice E) The norepinephrine alpha₂ receptor is located predominantly on presynaptic (not postsynaptic) nerve terminals throughout the CNS and the peripheral nervous system. Activation of these receptors inhibits norepinephrine release from the nerve terminal, inducing sympatholytic effects (eg, reduced heart rate, vasodilation). Educational objective: Glutamate is the main excitatory neurotransmitter of the CNS, inducing postsynaptic neuron depolarization and calcium entry through the NMDA receptor. Calcium entry programs the neuron to depolarize more robustly to repeated stimulation; this long-term potentiation forms a molecular basis for memory, learning, and addiction.

Researchers Find That Repeated Stimulation of Hippocampal Neurons Involved in Memory