Postsynaptic Calcium Influx at Single Synaptic Contacts between Pyramidal Neurons and Bitufted Interneurons in Layer 2/3 of Rat Neocortex Is Enhanced by Backpropagating Action Potentials

Abstract

Pyramidal neurons in layer 2/3 (L2/3) of the rat somatosensory cortex excite somatostatin-positive inhibitory bitufted interneurons located in the same cortical layer via glutamatergic synapses. A rise in volume-averaged dendritic [Ca²⁺]_i evoked by backpropagating action potentials (APs) reduces glutamatergic excitation via a retrograde signal, presumably dendritic GABA. To measure the rise in local [Ca²⁺]_i at synaptic contacts during suprathreshold excitation, we identified single synaptic contacts in the acute slice preparation in pairs of pyramidal and bitufted cells each loaded with a Ca²⁺ indicator dye. Repetitive APs (10-15 APs at 50 Hz) evoked in a L2/3 pyramidal neuron gave rise to facilitating unitary EPSPs in the bitufted cell. Subthreshold EPSPs evoked a transient rise in [Ca²⁺]_i of 80-250 nm peak amplitude at the postsynaptic dendritic site. The local postsynaptic [Ca²⁺]_i transient was restricted to ∼10 μm of dendritic length, lasted for ∼200 msec, and was mediated predominantly by NMDA receptor channels. When EPSPs were suprathreshold, the evoked AP backpropagated into the apical and basal dendritic arbor and increased the local [Ca²⁺]_i transient at active contacts by approximately twofold, with a peak amplitude reaching 130-450 nm. This value is in the range of the half-maximal dendritic [Ca²⁺]_i, evoking retrograde inhibition of glutamate release from boutons of pyramids. The localized enhancement of dendritic Ca²⁺ influx at synaptic contacts by synaptically evoked backpropagating APs could represent one mechanism by which a retrograde signal can limit the excitation of bitufted interneurons by L2/3 pyramids when these are repetitively active.