GABAA receptors at hippocampal mossy fibers

Presynaptic GABA(A) receptors modulate synaptic transmission in several areas of the CNS but are not known to have this action in the cerebral cortex. We report that GABAA receptor activation reduces hippocampal mossy fibers excitability but has the opposite effect when intracellular Cl(-) is experimentally elevated. Synaptically released GABA mimics the effect of exogenous agonists. GABA(A) receptors modulating axonal excitability are tonically active in the absence of evoked GABA release or exogenous agonist application. Presynaptic action potential-dependent Ca(2+) transients in individual mossy fiber varicosities exhibit a biphasic dependence on membrane potential and are altered by GABA(A) receptors. Antibodies against the alpha(2) subunit of GABA(A) receptors stain mossy fibers. Axonal GABAA receptors thus play a potentially important role in tonic and activity-dependent heterosynaptic modulation of information flow to the hippocampus.