Kainate receptors regulate unitary IPSCs elicited in pyramidal cells by fast-spiking interneurons in the neocortex

Unitary IPSCs elicited by fast-spiking (FS) interneurons in layer V pyramid al cells of the neocortex were studied by means of dual whole-cell recordin gs in acute slices. FS to pyramidal cell unitary IPSCs were depressed by (R S)-S-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl) (ATPA), a kainate (KA) re ceptor agonist, and by the endogenous agonist L-glutamate in the presence o f AMPA, NMDA, mGluR, and GABA(B) receptor antagonists. This effect was acco mpanied by an increase in failure rate of synaptic transmission, in the coe fficient of variation, and in the paired pulse ratio, indicating a presynap tic origin of the IPSC depression. Pairing the activation of the presynapti c neuron with a depolarization of the postsynaptic cell mimicked the decrea se of unitary IPSCs, and this effect persisted when postsynaptic sodium act ion potentials were blocked with the local anesthetic QX314. The effects of ATPA, glutamate, and of the pairing protocol were almost totally blocked b y CNQX. These data suggest that KA receptors located on presynaptic FS cell terminals decrease the release of GABA and can be activated by glutamate r eleased from the somatodendritic compartment of the postsynaptic pyramidal cells.