What makes the NMDA receptor act as a 'coincidence detector' during LTP induction?
AIt opens only when intracellular Ca²⁺ levels are already elevated
BIt requires both glutamate binding (presynaptic activity) AND postsynaptic depolarization to conduct current
CIt is activated only by high-frequency stimulation, never by single action potentials
DIt can only open after it physically associates with CaMKII
At resting membrane potential, a Mg²⁺ ion physically blocks the NMDA receptor channel even when glutamate is bound. The Mg²⁺ block is only relieved when the postsynaptic membrane is sufficiently depolarized (by summed AMPA receptor activity). This dual requirement — glutamate present AND postsynaptic depolarization — means the NMDA receptor only passes current when the pre- and postsynaptic cells are active simultaneously, the molecular implementation of Hebb's rule.
Question 2 True / False
Long-term potentiation increases synaptic strength primarily by inserting additional AMPA receptors into the postsynaptic density.
TTrue
FFalse
Answer: True
CaMKII, activated by Ca²⁺ influx through unblocked NMDA receptors, both phosphorylates existing AMPA receptors (increasing their conductance) and traffics additional AMPA receptors from intracellular pools to the postsynaptic membrane. More AMPA receptors means a larger EPSC for the same amount of glutamate released, which is the cellular mechanism underlying the potentiated synapse.
Question 3 Short Answer
Why does LTP induction require high-frequency stimulation rather than a single presynaptic action potential?
Think about your answer, then reveal below.
Model answer: A single presynaptic spike produces only a small EPSP via AMPA receptors, which is insufficient to depolarize the postsynaptic membrane enough to relieve the Mg²⁺ block from NMDA receptors. High-frequency stimulation causes temporal summation of EPSPs, achieving the threshold depolarization needed to expel Mg²⁺ and allow Ca²⁺ influx through NMDA receptors.
Temporal summation during rapid firing is the mechanism by which high-frequency protocols (e.g., 100 Hz tetanic stimulation) cross the depolarization threshold required to unblock NMDA receptors. This is directly connected to the concept of EPSP summation from postsynaptic currents — the NMDA receptor's Mg²⁺ block acts as a gate that only opens when summated inputs are strong enough.