Abstracts

Phasic and tonic inhibitions are mediated by synaptic and extrasynaptic GABA[sub]A[/sub] receptors, respectively. Extrasynaptic receptors respond to ambient levels of GABA thought to originate in part from spillover after vesicular release. If both phasic and tonic inhibitions are activated by vesicular GABA release, in any given cell there should be a correlation between the magnitudes of the two types of inhibition., Whole-cell voltage-clamp recordings were obtained from hippocampal CA1 pyramidal cells and from molecular layer interneurons. In order to measure tonic and phasic inhibitions simultaneously over short periods of time (1 s), we developed a new method of measurement of their mean values (Imean). In addition, simulations of sIPSCs were used to model specific changes in phasic currents., Simulations of sIPSC showed that this new method is highly sensitive and can detect the combined effects of small changes ([sim]15%) in two sIPSC properties (e.g., amplitude and decay time constant) even when the change in each individual parameter is not statistically significant. Using this method we investigated changes in phasic and tonic inhibitions during spontaneous and sucrose induced bursts of sIPSCs recorded in hippocampal interneurons and pyramidal cells. During the bursts there was a large increase ([sim]52 Hz) of sIPSC frequency with a concomitant change in baseline holding current. However, simulations of sIPSC bursts even at much higher frequencies than those actually recorded showed only a minimal contribution of phasic inhibition to the baseline current, thus indicating that tonic inhibition was also activated during the bursts. In addition, we found a strong cross-correlation between phasic and tonic inhibitions when vesicular GABA release was reduced by perfusing TTX + CdCl[sub]2[/sub]., These results are consistent with a significant portion of tonic inhibition being mediated by GABA released from the very vesicles responsible for activating phasic inhibition. Therefore, phasic and tonic inhibitions can be modulated in unison resulting in a compound dampening effect on neuronal excitability., (Supported by the Gonda Fellowship to J.G. and by NS02808, NS30549 and the Coelho Endowment to I.M.)