alpha 5GABA(A) receptors regulate the intrinsic excitability of mouse hippocampal pyramidal neurons

作者：Bonin Robert P; Martin Loren J; MacDonald John F; Orser Beverley A^*

来源：Journal of Neurophysiology, 2007, 98(4): 2244-2254.

DOI：10.1152/jn.00482.2007

GABA(A) receptors generate both phasic and tonic forms of inhibition. In hippocampal pyramidal neurons, GABA A receptors that contain the alpha 5 subunit generate a tonic inhibitory conductance. The physiological role of this tonic inhibition is uncertain, although alpha 5GABA(A) receptors are known to influence hippocampal-dependent learning and memory processes. Here we provide evidence that alpha 5GABA A receptors regulate the strength of the depolarizing stimulus that is required to generate an action potential in pyramidal neurons. Neurons from alpha 5 knock-out (alpha 5-/-) and wild-type (WT) mice were studied in brain slices and cell cultures using whole cell and perforated-patch-clamp techniques. Membrane resistance was 1.6-fold greater in alpha 5-/- than in WT neurons, but the resting membrane potential and chloride equilibrium potential were similar. Membrane hyperpolarization evoked by an application of exogenous GABA was greater in WT neurons. Inhibiting the function of alpha 5GABA(A) receptor with nonselective (picrotoxin) or alpha 5 subunit-selective (L-655,708) compounds depolarized WT neurons by similar to 3 mV, whereas no change was detected in alpha 5-/- neurons. The depolarizing current required to generate an action potential was twofold greater in WT than in alpha 5-/- neurons, whereas the slope of the input-output relationship for action potential firing was similar. We conclude that shunting inhibition mediated by alpha 5GABA(A) receptors regulates the firing of action potentials and may synchronize network activity that underlies hippocampal-dependent behavior.

• 出版日期2007-10
• 单位河北医科大学