Instructive signals drive learning through behavioral timescale synaptic plasticity in the hippocampus and beyond

Abstract

Learning requires the brain to link experience to lasting changes in neural activity, yet most experiences unfold over timescales far longer than those of classical synaptic plasticity mechanisms. Behavioral timescale synaptic plasticity (BTSP) has emerged as a candidate mechanism that bridges this gap by enabling rapid, one-shot modification of synaptic strength at the seconds timescale. BTSP is driven by dendritic Ca2+ plateau potentials (“plateaus”) and potentiates inputs active within a seconds-long window surrounding the plateau, providing a mechanism for the rapid formation and updating of hippocampal place cell representations. Here, we review recent experimental and theoretical advances in BTSP, with a particular focus on the origin and function of the instructive signal from medial entorhinal cortex layer 3 (MEC3) that drives plateau generation in CA1 pyramidal neurons. We discuss evidence that this instructive signal may interact with elements of the hippocampal microcircuit to shape learning-dependent representations. Beyond the hippocampus, emerging findings indicate that BTSP-like mechanisms may operate in other cortical regions, suggesting that integrating signals across dendritic compartments may represent a more general motif for rapid learning. Together, these observations support a view of BTSP as a multi-factor plasticity rule that links synaptic, circuit, and systems-level processes, providing a biologically grounded framework for understanding how the brain rapidly incorporates new information.