Postsynaptic glutamate receptors and integrative properties of fast-spiking interneurons in the rat neocortex

The glutamate-mediated synaptic responses of neocortical pyramidal cell to fast-spiking interneuron (pyramidal-FS) connections were studied by perform ing paired recordings at 30-33 degrees C in acute slices of 14- to 35-day-o ld rats (n = 39). Postsynaptic fast-spiking (FS) cells were recorded in who le cell configuration with a patch pipette, and presynaptic pyramidal cells were impaled with sharp intracellular electrodes. At a holding potential o f -72 mV (near the resting membrane potential), unitary excitatory postsyna ptic potentials (EPSPs) had a mean amplitude of 2.1 +/- 1.3 mV and a mean w idth at half-amplitude of 10.5 +/- 3.7 ms (n = 18). Bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D(-)2-amino-5-phosphonoval eric acid (D-AP5) had minor effects on both the amplitude and the duration of unitary EPSPs, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-pr opionate (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX) almost completely blocked the synaptic responses. In voltage-c lamp mode, the selective antagonist of AMPA receptors 1-(4-aminophenyl)-3-m ethylcarbamyl-4-methyl-7, 8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepin e (GYKI 53655; 40-66 mu M) blocked 96 +/- 1.9% of D-APS-insensitive unitary excitatory postsynaptic currents (EPSCs), confirming the predominance of A MPA receptors, as opposed to kainate receptors, at pyramidal-FS connections (n = 3). Unitary EPSCs mediated by AMPA receptors had fast rise times (0.2 9 +/- 0.04 ms) and amplitude weighted decay time constants (2 +/- 0.8 ms; n = 16). In the presence of intracellular spermine, these currents showed th e characteristic rectifying current-voltage (I-V) curve of calcium-permeabl e AMPA receptors. A slower component mediated by NMDA receptors was observe d when unitary synaptic currents were recorded at a membrane potential more positive than -50 mV. In response to short trains of moderately high-frequ ency (67 Hz) presynaptic action potentials, we observed only a limited temp oral summation of unitary EPSPs, probably because of the rapid kinetics of AMPA receptors and the absence of NMDA component in these subthreshold syna ptic responses. By combining paired recordings with extracellular stimulati ons (n = 11), we demonstrated that EPSPs elicited by two different inputs w ere summed linearly by FS interneurons at membrane potentials below the act ion potential threshold. We estimated that, in our in vitro recording condi tions, 8 +/- 5 pyramidal cells (n = 18) should be activated simultaneously to make FS interneurons fire an action potential from -72 mV. The low level of temporal summation and the linear summation of excitatory inputs in FS cells favor the role of coincidence detectors of these interneurons in neoc ortical circuits.