Functional regulation of the dentate gyrus by GABA-mediated inhibition

Abstract

Dentate granule cells are characterized by their low levels of excitability, an important aspect of hippocampal function, which distinguishes them from other principal cells of the hippocampus. This low excitability derives in large part from the degree and nature of GABAergic inhibition evident in the dentate gyrus. Granule cells express a unique and complex assortment of GABA(A) receptor subunits, found in few areas of the brain. Associated with this receptor complexity, granule cells are endowed with both synaptic and extrasynaptic GABA(A) receptors with distinctive properties. In particular, extrasynaptic GABA(A) receptors in granule cells exhibit high affinity for GABA and do not desensitize. This results in activation of a tonic current by ambient levels of GABA present in the extracellular space. This tonic current contributes significantly to the circuit properties of the dentate gyrus. Both synaptic and extrasynaptic GABA(A) receptors exhibit profound dysregulation in animal models of temporal lobe epilepsy, which may contribute to the hippocampal hyperexcitability that defines this disorder.