Martin LJ, Zurek AA, MacDonald JF, Roder JC, Jackson MF, Orser BA. (2010) J Neurosci. 30(15):5269-82.

Abstract

Synaptic plasticity, which is the neuronal substrate for many forms of hippocampus-dependent learning, is attenuated by GABA type A receptor (GABA_AR)-mediated inhibition. The prevailing notion is that a synaptic or phasic form of GABAergic inhibition regulates synaptic plasticity; however, little is known about the role of GABA_AR subtypes that generate a tonic or persistent inhibitory conductance. We studied the regulation of synaptic plasticity by α5 subunit-containing GABA_ARs (α5GABA_ARs), which generate a tonic inhibitory conductance in CA1 pyramidal neurons using electrophysiological recordings of field and whole-cell potentials in hippocampal slices from both wild-type and null mutant mice for the α5 subunit of the GABA_AR (Gabra5-/- mice). In addition, the strength of fear-associated memory was studied. The results showed that α5GABA_AR activity raises the threshold for induction of long-term potentiation in a highly specific band of stimulation frequencies (10-20 Hz) through mechanisms that are predominantly independent of inhibitory synaptic transmission. The deletion or pharmacological inhibition of α5GABA_ARs caused no change in baseline membrane potential or input resistance but increased depolarization during 10 Hz stimulation. The encoding of hippocampus-dependent memory was regulated by α5GABA_ARs but only under specific conditions that generate moderate but not robust forms of fear-associated learning. Thus, under specific conditions, α5GABA_AR activity predominates over synaptic inhibition in modifying the strength of both synaptic plasticity in vitro and certain forms of memory in vivo.

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