Postsynaptic spiking determines anti-Hebbian LTD in visual cortex basket cells

Abstract

Long-term plasticity at pyramidal cell to basket cell (PC → BC) synapses is important for the functioning of cortical microcircuits. It is well known that at neocortical PC → PC synapses, dendritic calcium (Ca²⁺) dynamics signal coincident pre-and postsynaptic spiking which in turn triggers long-term potentiation (LTP). However, the link between dendritic Ca²⁺ dynamics and long-term plasticity at PC → BC synapses of primary visual cortex (V1) is not as well known. Here, we explored if PC → BC synaptic plasticity in developing V1 is sensitive to postsynaptic spiking. Two-photon (2P) Ca²⁺ imaging revealed that action potentials (APs) in dendrites of V1 layer-5 (L5) BCs back-propagated decrementally but actively to the location of PC → BC putative synaptic contacts. Pairing excitatory inputs with postsynaptic APs elicited dendritic Ca²⁺ supralinearities for pre-before-postsynaptic but not post-before-presynaptic temporal ordering, suggesting that APs could impact synaptic plasticity. In agreement, extracellular stimulation as well as high-throughput 2P optogenetic mapping of plasticity both revealed that pre-before-postsynaptic but not post-before-presynaptic pairing resulted in anti-Hebbian long-term depression (LTD). Our results demonstrate that V1 BC dendritic Ca²⁺ nonlinearities and synaptic plasticity at PC → BC connections are both sensitive to somatic spiking.

Keywords: action potential backpropagation; calcium imaging; inhibitory interneurons; plasticity; spike-timing dependent plasticity; synapse; visual cortex.