alpha 5GABA(A) Receptor Activity Sets the Threshold for Long-Term Potentiation and Constrains Hippocampus-Dependent Memory

作者：Martin Loren J; Zurek Agnieszka A; MacDonald John F; Roder John C; Jackson Michael F; Orser Beverley A^*

来源：Journal of Neuroscience, 2010, 30(15): 5269-5282.

DOI：10.1523/JNEUROSCI.4209-09.2010

Synaptic plasticity, which is the neuronal substrate for many forms of hippocampus-dependent learning, is attenuated by GABA type A receptor (GABA(A)R)-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(A)R subtypes that generate a tonic or persistent inhibitory conductance. We studied the regulation of synaptic plasticity by alpha 5 subunit-containing GABA(A)Rs (alpha 5GABA(A)Rs), 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 alpha 5 subunit of the GABA(A)R (Gabra5(-/-) mice). In addition, the strength of fear-associated memory was studied. The results showed that alpha 5GABA(A)R 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 alpha 5GABA(A)Rs 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 alpha 5GABA(A)Rs but only under specific conditions that generate moderate but not robust forms of fear-associated learning. Thus, under specific conditions, alpha 5GABA(A)R activity predominates over synaptic inhibition in modifying the strength of both synaptic plasticity in vitro and certain forms of memory in vivo.

• 出版日期2010-4-14
• 单位河北医科大学