Somatic and Dendritic Actions of ~-aminobutyri~ Acid Agonists and Uptake Blockers in the Hippocampus in Vw0

In rats under urethane anaesthesia y-aminobutyric acid agonists and uptake blockers were microiontophoretically applied in the pyramidal layer of CA1 and in the apical dendrites using a twin set of multibarrelled micropipettes. Thus, the somatic and dendritic field potentials elicited by commissural stimulation were recorded simultaneously and the effects of iontophoretic applications at either site studied. Somatic applications of ~-aminobut~~ acid, isoguvacine or muscimol produced an inhibition of the somatic population spike; this showed rapid fade and was followed by an “off” response i.e. an enhancement of the population spike discharge and the occurrence of a second (and occasionally third) spike. The order of potency with regard to the “off” >>y-aminobutyric acid. In contrast, response was muscimol z isoguvacine the inhibition of the population spike produced by 4,5,6,7-tetrahydroisoxazolo(5,4-C) pyridin 3-OL showed little fade and no prominent “off” response. The fade and “off” response were not associated with significant changes in the dendritic field excitatory postsynaptic potential concommittantly recorded and were exclusively restricted to the immediate vicinity of the pyramidal layer. Ejection of ~-aminobutyric acid and its agonists in the stratum radiatum produced a reduction of the field excitatory postsynaptic potential and the somatic spike, this effect however showed no fade (even during prolonged applications of high doses) and no “off” response. Somatic applications of the uptake blockers nipecotic acid or guvacine consistently produced: (a) an increase in the effectiveness of the inhibition produced by y-aminobutyric acid and its analogues; (b) a decrease in the latency to peak of the inhibition and an increase in the time to recovery; (c) a full blockade of the fade and the “off” response. All of these effects were rapid and fully reversible without significant changes in either the field excitatory postsynaptic potential or the (control) somatic spikes. The more specific ghal uptake blocker, 4,5,6,7-tetrahydroisoxazolo(4,5-C) ovridin 3-OL occasionallv blocked the , ., “off” response, however it was less potent and also tended to reduce the spike amplitude. Dendritic applications of the uptake blockers reduced the excitatory postsynaptic potential and the somatic spike but failed to produce prominent changes in the action of y-aminobutyric acid and its analogues. Somatic, but not dendritic, applications of nipecotic acid or guvacine effectively reduced the enhancement of the spikes which is easily evoked in this preparation by an increase of the frequency of stimulation. These observations suggest that removal of y -aminobutyric acid in the pyramidal layer is highly efficient; the possibility that this plays a role in the susceptibility of the hippocampus to epileptogenic procedures is discussed. In keeping with earlier biochemical48 and immunocytochemicaP data, recent electrophysiolo~cal studies in the hippocampus performed both in sitd and in vitro’.Z,M have provided direct evidence that y-aminobutyric acid (CABA) mediates the powerful inhibition first described in the hippocampus by Kandel et ~1.‘~ (see also ref. 3). As in other brain structures’4 iontophoretic applications of GABA at the soma produces a hy~rpolarization which is associated with an increase in chloride permeability. ‘v2.’ However, in vitro the dendritic application of GABA in this structure leads to a depolar-