Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning

Synaptic plasticity underlies learning by modifying specific synaptic inputs to reshape neural activity and behavior. However, the rules governing which synapses will undergo different forms of plasticity in vivo during learning and whether these rules are uniform within individual neurons remain unclear. Using in vivo longitudinal imaging with single-synapse resolution in the mouse motor cortex during motor learning, we found that apical and basal dendrites of layer 2/3 (L2/3) pyramidal neurons showed distinct activity-dependent synaptic plasticity rules. The strengthening of apical and of basal synapses is predicted by local coactivity with nearby synapses and activity coincident with postsynaptic action potentials, respectively. Blocking postsynaptic spiking diminished basal synaptic potentiation without affecting apical plasticity. Thus, individual neurons use multiple activity-dependent plasticity rules in a compartment-specific manner in vivo during learning.