Acute ethanol modulates an incredibly diverse number of neurotransmitter receptors and intracellular pathways. Presynaptic modulation by acute ethanol has been identified at some GABAergic synapses; but descriptions of acute ethanol regulation of presynaptic glutamatergic function are sparse. Recent reports suggest that acute ethanol can inhibit glutamatergic synaptic responses arising from recycling vesicles during tetanic stimulation of Stria terminalis inputs onto basolateral amygdala (BLA) principal neurons. This finding gives rise to the hypothesis that acute ethanol may modulate actively priming synaptic vesicles in glutamate synapses. To test this, we used whole cell patch clamp recordings in BLA principal neurons and measured the effects of acute ethanol on asynchronous synaptic transmission. We found Stria teminalis inputs express EGTA-sensitive asynchronous synaptic glutamatergic responses produced from both increased presynaptic activation and experimental elevation of presynaptic calcium using partial substitution of extracellular Na + with Li + . Under both conditions, asynchronous events were acutely inhibited by ethanol in a concentration-dependent fashion. Ethanol inhibition of asynchronous glutamate release was present in DBA/2J Stria terminalis synapses but absent when measuring inputs in C57BL/6J mice. EGTA, which robustly suppresses expression of asynchronous release, also occluded ethanol modulation under both conditions. Surprisingly, EGTA did not alter the expression or occlude ethanol modulation of synaptic responses arising from recycling vesicles. Our findings demonstrate a unique acute effect of ethanol on asynchronous glutamate vesicle priming pathways. • Glutamate inputs onto basolateral amygdala principal neurons express activity-dependent asynchronous glutamate release that is inhibited by acute ethanol • Ethanol also inhibits asynchronous glutamate release produced by partial substitution of extracellular lithium for sodium • EGTA-AM treatment blocks the expression of asynchronous glutamate release and occludes ethanol inhibition
Parrish et al. (Sun,) studied this question.