AMPA receptor channels with long-lasting desensitization in bipolar interneurons contribute to synaptic depression in a novel feedback circuit in layer 2/3 of rat neocortex

A novel, local inhibitory circuit in layer 2/3 of rat somatosensory cortex is described that connects pyramidal cells reciprocally with GABAergic vaso active intestinal polypeptide-immunoreactive bipolar interneurons. In paire d whole-cell recordings, the glutamatergic unitary responses (EPSPs or EPSC s) in bipolar cells evoked by repetitive (10 Hz) stimulation of a pyramidal cell show strong frequency-dependent depression. Unitary IPSPs evoked in p yramidal cells by repetitive stimulation of bipolar cells, on average, main tained their amplitude. This suggests that the excitatory synapses on bipol ar cells act as a low-pass filter in the reciprocal pyramid-to-bipolar circ uit. The EPSCs in bipolar cells are mediated predominantly by AMPA receptor (AMPAR) channels. AMPARs desensitize rapidly and recover slowly from desen sitization evoked by a brief pulse of glutamate. In slices, reduction of AM PAR desensitization by cyclothiazide (50-100 muM) or conditioning steady-st ate desensitization induced by application of extracellular AMPA (50 nM) or glutamate (50 muM) strongly reduced synaptic depression. It is concluded t hat in the local circuits between pyramidal and bipolar cells the desensiti zation of AMPARs in bipolar cells contributes to low-pass feedback inhibiti on of layer 2/3 pyramidal neurons by bipolar cells.