Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex

1. Dual whole-cell recordings were made in layer 2/3 of the rat neocortex in synaptically connected pyramidal cells and fast-spiking non-accommodating (FSN) interneurons. In 75% of cell pairs (n = 80), the cells formed reciprocal synaptic connections. 2. Trains of backpropagating action potentials in pyramidal cells induced Ca2+ transients in dendrites followed by inhibition of unitary IPSPs. IPSP depression was prevented by loading pyramidal cells with 5 mM BAPTA or EGTA. 3. IPSP depression was mimicked by the metabotropic glutamate receptor (mGluR) agonist ACPD and was prevented by a mixture of the mGluR antagonists CPCCOEt and EGLU. 4. IPSP depression was prevented by loading pyramidal cells with the antagonists of vesicular exocytosis botulinum toxin D (light chain) and GDP-beta -S. 5. It is concluded that Ca2+-dependent release of a retrograde messenger, most probably glutamate, from pyramidal cell dendrites suppresses the inhibition of pyramidal neurons via activation of mGluRs located in FSN interneuron nerve terminals.