BTSP, not STDP, Drives Shifts in Hippocampal Representations During Familiarization.

Synaptic plasticity is widely thought to support memory storage in the brain, but the rules determining impactful synaptic changes in-vivo are not known. We considered the trial-by-trial shifting dynamics of hippocampal place fields (PFs) as an indicator of ongoing plasticity during memory formation. By implementing different plasticity rules in computational models of spiking place cells and comparing to experimentally measured PFs from mice navigating familiar and novel environments, we found that Behavioral-Timescale-Synaptic-Plasticity (BTSP), rather than Hebbian Spike-Timing-Dependent-Plasticity, is the principal mechanism governing PF shifting dynamics. BTSP-triggering events are rare, but more frequent during novel experiences. During exploration, their probability is dynamic: it decays after PF onset, but continually drives a population-level representational drift. Finally, our results show that BTSP occurs in CA3 but is less frequent and phenomenologically different than in CA1. Overall, our study provides a new framework to understand how synaptic plasticity shapes neuronal representations during learning.