Summary
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 novel 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.
AbstractEpisodic memory requires linking events in time, a function dependent on the hippocampus. In “trace” fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use 2-photon calcium imaging to track neural population dynamics over the complete time-course of learning and show that, in contrast to previous theories, the hippocampus does not generate persistent activity to bridge the time delay. Instead, learning is concomitant with broad changes in the active neural population in CA1. While neural responses were highly stochastic in time, cue identity could be reliably read out from population activity rates over longer timescales after learning. These results question the ubiquity of neural sequences during temporal association learning, and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.
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