SPONTANEOUS GABA A RECEPTOR-MEDIATED INHIBITORY CURRENTS IN ADULT RAT SOMATOSENSORY CORTEX. SALIN, PAUL A., DAVID A. PRINCE. DEPARTMENT OF NEUROLOGY AND NEUROLOGICAL SCIENCES, STANFORD UNIVERSITY SCHOOL OF MEDICINE.
APStracts 2:0317N, 1995.
SUMMARY AND CONCLUSIONS
1. Spontaneous inhibitory synaptic currents (sIPSCs) were studied with whole- cell voltage-clamp recordings from 131 pyramidal cells in adult rat somatosensory cortical slices. Neurons were intracellulary labelled with biocytin and classfied as supragranular (SG, layers 2-3), layer IV (IV), or infragranular (IG, layer V) on the basis of the laminar localization of their somata. Somatic areas were similar for SG, IV, and IG neurons. All identified pyramidal cells generated high frequency GABA A receptor-mediated synaptic events. 2. Bath application of bicuculline blocked the sIPSCs, and resulted in a decrease of 0.5 nS in resting conductance and an inward shift in baseline current. 3. Spontaneous IPSC frequency was significantly lower in SG versus IG or IV neurons, and this difference was accounted for by the occurrence of a higher percentage of bursts of sIPSCs in the IG and IV neurons. 4. Bath application of the [alpha]-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA) receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) decreased the frequency of sIPSCs by 13-21%. By contrast, application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) generally had no effect on spontaneous IPSC frequency, suggesting that AMPA rather than NMDA receptor activation contributed to resting discharge of inhibitory interneurons. 5. Addition of tetrodotoxin (TTX) to the perfusion medium reduced the spontaneous IPSC frequency by about 30-55%. The miniature IPSCs (mIPSCs) seen in TTX-containing solutions had a frequency of about 10Hz and an average conductance of 0.42-0.48nS. 6. The kinetic properties of mIPSCs generated in pyramidal cells of different layers were the same, with the rise times of about 0.9 ms and decay time constants of about 8 ms at a holding potential of 0mV. The decay phase of mIPSCs was generally fitted by one exponential and displayed a voltage dependence with an e -fold increase in decay time constant for a every 198 mV depolarization. 7. These results show that there is ongoing spontaneous release of GABA in neocortical slices that gives rise to high frequency impulse-related and non-impulse- related postsynaptic inhibitory currents. Activation of AMPA receptors on inhibitory interneurons accounts for only a small proportion of the GABA A receptor-mediated events. Judging from the distribution of mIPSC frequencies in neurons of different laminae, there is a relatively uniform distribution of inhibitory synapses throughout the cortex. Tonic activation of GABA A receptors on neocortical pyramidal neurons generates an increase in resting membrane conductance that may play an important role in vivo by preventing the development of hyperexcitability, modulating excitatory synaptic events, and controlling the rate and patterns of spike discharge. 

Received 5 April 1995; accepted in final form 20 October 1995.
APS Manuscript Number J227-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95