Recruitment of GABA A inhibition in rat neocortex is limited and not NMDA- dependent. Ling, Douglas S. F. and Larry S. Benardo. Departments of Pharmacology and Neurology, State University of New York - Health Science Center at Brooklyn, Brooklyn, NY 11203 (U.S.A.).
APStracts 2:0207N, 1995.
SUMMARY AND CONCLUSIONS
1 . The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) was examined using whole-cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex. Synaptic currents were evoked with graded electrical stimulation to assess the relative activation of IPSCs and EPSCs. Fast GABA A ergic IPSCs were selectively recorded by holding cells at potentials equal to EPSC reversal (0 ? mV). EPSCs were likewise isolated by holding cells at IPSC reversal ( ? -75 ? mV). 2 . As stimulus intensities were increased, the magnitude of the postsynaptic currents also increased. Over the range of stimuli applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast GABA A -mediated IPSCs reached a maximum at intensities approximately 2X threshold. 3 . The limit on fast inhibition was unresponsive to alterations in NMDA-mediated excitation. Exposure to nominally magnesium-free solutions or to the NMDA antagonist CPP did not affect the fast IPSC maximum. Shifts in the input-output curves for submaximal activation of IPSCs were seen, which were attributed to polysynaptic excitation. 4 . Blockade of AMPA/kainate (non- NMDA) receptors with CNQX completely abolished synaptically driven, fast GABA A -mediated inhibition. These findings suggested that neocortical inhibitory cells could be driven exclusively through non-NMDA transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6 . The results in neocortex were corroborated by direct intracellular recordings from layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic activation of action potentials in these cells, even during co-treatment with magnesium-free solution. 7 . Together, these results suggest that recruitment of GABA A ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents arriving at non-NMDA receptors on interneurons. Properties limiting fast inhibition would favor the propagation of enhanced excitatory activity through the neuronal network. 

Received 30 March 1995; accepted in final form 18 July 1995.
APS Manuscript Number J211-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.