Recruitment of N-Type Ca2+ Channels during LTP Enhances Low Release Efficacy of Hippocampal CA1 Perforant Path Synapses

The entorhinal cortex provides both direct and indirect inputs to hippocampal CA1 neurons through the perforant path and Schaffer collateral synapses, respectively. Using both two-photon imaging of synaptic vesicle cycling and electrophysiological recordings, we found that the efficacy of transmitter release at perforant path synapses is lower than at Schaffer collateral inputs. This difference is due to the greater contribution to release by presynaptic N-type voltage-gated Ca2+ channels at the Schaffer collateral than perforant path synapses. Induction of long-term potentiation that depends on activation of NMDA receptors and L-type voltage-gated Ca2+ channels enhances the low efficacy of release at perforant path synapses by increasing the contribution of N-type channels to exocytosis. This represents a previously uncharacterized presynaptic mechanism for fine-tuning release properties of distinct classes of synapses onto a common postsynaptic neuron and for regulating synaptic function during long-term synaptic plasticity.