GABA(A)-MEDIATED IPSCS IN PIRIFORM CORTEX HAVE FAST AND SLOW COMPONENTS WITH DIFFERENT PROPERTIES AND LOCATIONS ON PYRAMIDAL CELLS

A recent study in piriform (olfactory) cortex provided evidence that, as in hippocampus and neocortex, gamma-aminobutyric acid-A (GABA(A))-m ediated inhibition is generated in dendrites of pyramidal cells, not j ust in the somatic region as previously believed. This study examines selected properties of GABA(A) inhibitory postsynaptic currents (IPSCs ) in dendritic and somatic regions that could provide insight into the ir functional roles. Pharmacologically isolated GABA(A)-mediated IPSCs were studied by whole cell patch recording in slices. To compare prop erties of IPSCs in distal dendritic and somatic regions, local stimula tion was carried out with tungsten microelectrodes, and spatially rest ricted blockade of GABA(A)-mediated inhibition was achieved by pressur e-ejection of bicuculline from micropipettes. The results revealed tha t largely independent circuits generate GABA(A) inhibition in distal a pical dendritic and somatic regions. With such independence, a selecti ve decrease in dendritic-region inhibition could enhance integrative o r plastic processes in dendrites while allowing feedback inhibition in the somatic-region to restrain system excitability. This could allow modulatory fiber systems from the basal forebrain or brain stem, for e xample, to change the functional state of the cortex by altering the e xcitability of interneurons that mediate dendritic inhibition without increasing the propensity for regenerative bursting in this highly epi leptogenic system. As in hippocampus, GABA(A)-mediated IPSCs were foun d to have fast and slow components with time constants of decay on the order of 10 and 40 ms, respectively, at 29 degrees C. Modeling analys is supported physiological evidence that the slow time constant repres ents a true IPSC component rather than an artifactual slowing of the f ast component from Voltage clamp of a dendritic current The results in dicated that, whereas both dendritic and somatic-region IPSCs have bot h fast and slow GABA(A) components, there is a greater proportion of t he slow component in dendrites. In a companion paper, the hypothesis i s explored that the resulting slower time course of the dendritic IPSC increases its capacity to regulate the N-methyl-D-aspartate component of EPSPs. Finally, evidence is presented that the slow GABA(A)-mediat ed IPSC component is regulated by presynaptic GABA(B) inhibition where as the fast is not. Based on the requirement for presynaptic GABA(B)-m ediated block of inhibition for expression of long-term potentiation, this finding is consistent with participation of the slow GABA(A) comp onent in regulation of synaptic plasticity. The lack of susceptibility of the fast GABA(A) component to the long-lasting, activity-induced s uppression mediated by presynaptic GABA(B) receptors is consistent wit h a protective role for this process in preventing seizure activity.