Questions: Long-Term Potentiation (LTP): Synaptic Strengthening

Question 1

What makes NMDA receptors function as 'coincidence detectors' during LTP induction?

• A. They open whenever glutamate binds, regardless of postsynaptic voltage
• B. They require both presynaptic glutamate release and postsynaptic depolarization to relieve Mg2+ block and allow Ca2+ influx
• C. They activate only after repeated stimulation over several hours
• D. They respond only to GABA, not glutamate, at the synapse

Answer: (B)

At resting potential, a Mg2+ ion physically blocks the NMDA receptor channel. Glutamate binding alone is insufficient — the postsynaptic membrane must also be depolarized (typically by AMPA receptor activation) to expel the Mg2+ block. Only when BOTH conditions are met does Ca2+ flow in. This 'and gate' logic is what makes NMDA receptors molecular coincidence detectors implementing Hebbian learning.

Question 2

During LTP induction, the calcium influx through NMDA receptors leads to removal of AMPA receptors from the postsynaptic membrane, weakening the synapse.

• T. True
• F. False

Answer: False

The opposite is true. Calcium influx activates CaMKII and other kinases, which trigger the insertion of additional AMPA receptors into the postsynaptic membrane — specifically to the synapse from intracellular pools. More AMPA receptors means greater depolarization in response to the same glutamate release, which is the cellular basis of synaptic strengthening in LTP.

Question 3

Why is LTP described as a cellular model of associative learning, and which aspect of its mechanism supports this interpretation?

Model answer: LTP is associative because a synapse is strengthened only when pre- and postsynaptic activity coincide — implementing the Hebbian principle 'neurons that fire together, wire together.' The NMDA receptor's requirement for simultaneous glutamate binding AND postsynaptic depolarization enforces this co-activity requirement at the molecular level.

Classical conditioning requires that a neutral stimulus (CS) become associated with an unconditioned stimulus (US). LTP provides a mechanism: if two inputs converge on the same neuron simultaneously, their synapses are strengthened selectively. This selectivity arises from the Mg2+ block — weak or asynchronous activation cannot lift it. The NMDA receptor thus physically instantiates the 'coincidence' requirement that associative learning demands.