Axonal GABAA receptors

Type A GABA receptors (GABAARs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABAARs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABAARs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABAAR modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABAARs 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 GABAARs 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 GABAARs persist into adulthood. Altogether, axonal GABAARs appear as potent neuronal modulators of the mammalian CNS.