Synaptic Basis of Behavioral Timescale Plasticity

Abstract Learning and memory are fundamental to adaptive behavior and cognition. Various forms of synaptic plasticity have been proposed as cellular substrates for the emergence of feature selectivity in neurons underlying episodic memory. However, despite decades of work, our understanding of how synaptic plasticity underlies memory encoding remains limited, largely due to a shortage of tools and technical challenges associated with the visualization of synaptic plasticity at single-neuron resolution in awake-behaving animals. Behavioral Timescale Synaptic Plasticity (BTSP) postulates that synaptic inputs active during a seconds-long time window preceding and immediately following a large depolarizing plateau spike are potentiated, while synaptic inputs active outside this time window are depressed. We experimentally tested this model in vivo in awake-behaving mice using an all-optical approach by inducing place fields (PFs) in single CA1 pyramidal neurons (CA1PNs) while monitoring the spatiotemporal tuning of individual dendritic spines and changes in their corresponding synaptic weights. We identified an asymmetric synaptic plasticity kernel resulting from bidirectional modifications of synaptic weights around plateau burst induction. Surprisingly, our work also uncovered compartment-specific differences in the magnitude and temporal expression of synaptic plasticity between basal and oblique dendrites of CA1PNs. Our results provide the first experimental evidence linking synaptic plasticity to the rapid emergence of spatial selectivity in hippocampal neurons, a critical prerequisite for episodic memory.