Axonal GABAA receptors

Type A GABA receptors (GABA_ARs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA_ARs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA_ARs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA_AR modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA_ARs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA_ARs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA_ARs persist into adulthood. Altogether, axonal GABA_ARs appear as potent neuronal modulators of the mammalian CNS.