Synaptic inhibition in the rat hippocampus : investigation of the actions of 2-hydroxy-saclofen

• Main Author: Caddick, Sarah Jane
• Other Authors: Chad, John
• Published: University of Southampton 1993
• Subjects: 615.1; QH301 Biology
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295677

In the hippocampus, aminobutyric acid (GABA) acts as an inhibitory neurotransmitter via ligand gated GABA_A and G protein -coupled GABA_B receptors. GABA can also inhibit synaptic transmission via activation of presynaptic GABA_B receptors on the terminals of local interneurones and excitatory afferents. These multiple sites of control allow a number of possibilities for modulation of physiological and pathological processes. In order to address the role of inhibition in the modulation of excitatory transmission, standard extracellular techniques were used to record population spikes from CAI pyramidal cells in response to stimulation of afferent fibre tracts. Two components of inhibition, GABA_A (10-30msec) and GBA_B (300msec) were measured which could be blocked by bicuculline and phaclofen respectively. The selective GABA_b antagonist 2-hydroxy-saclofen (2-OH-S) was used to investigate inhibition mediated by GABA_B receptors. In addition to attenuating the late inhibition 2-OH-S unexpectedly depressed the conditioning response and the early inhibition. These effects could be blocked by phaclofen but not bicuculline suggesting that increased activation of GABA_A receptors due to disinhibition of inhibitory interneurones was not involved. To investigate these anomalous effects and the physiological role of pre and postsynaptic inhibition mediated by GABA_B receptors, isolated IPSC's were recorded from single CAI pyramidal cells. The IPSC_A and IPSC_B were both depressed by 2-OH-S. The latency to peak of the IPSC_A correlated with the latency to peak of the early inhibition. However the latency to peak of the IPSC_B (175msec) was less than the latency to peak of the late inhibition (300msec), which was similar to the latency to peak of the paired pulse depression of the EPSC. With the postsynaptic K^+ channel blocked, both 2-OH-S and baclofen depressed the EPSC via activation of presynaptic GABA_B receptors. Unlike baclofen, there appeared to be no evidence for an action of 2-OH-S at the postsynaptic site in any of these experiments. These results could be explained by a partial agonist action of 2-OH-S at presynaptic GABA_B receptors.