Ethanol Differentially Affects Excitatory and Inhibitory Synaptic Transmission in Visual Cortex of Wild-type and Adenosine AR Knock-out Mice.

Ethanol is one of the most commonly used and abused substances in the world. While the behavioral effects of ethanol are well characterized, mechanisms of its action on neurons and synapses remain elusive. Prior research suggested that ethanol could affect neurons by interfering with metabolism of biologically active molecules, such as adenosine. Here, we explored the involvement of adenosine A receptors (AR) in mediating ethanol's effects on synaptic transmission to layer 2/3 pyramidal neurons of visual cortex using wild type (WT) and AR knock-out (KO) mice. Ethanol differentially affected excitatory and inhibitory transmission in WT and KO mice. In slices from WT mice ethanol had heterogeneous effects on excitatory transmission (facilitation, suppression or no change), with no net change. Ethanol's effects remained heterogeneous during acute blockade of A1Rs with a selective antagonist DPCPX. However, in ARKO mice ethanol consistently suppressed excitatory transmission, with no cases of enhancement observed. Inhibitory transmission was suppressed by ethanol in both WT and ARKO mice. At both excitatory and inhibitory synapses, changes of response amplitude correlated with changes of paired-pulse ratio, suggesting involvement of presynaptic mechanisms. We conclude that ARs are not involved in mediating effects of ethanol on synaptic transmission in mouse visual cortex. However, ARs are necessary for development of mechanisms mediating facilitation at some excitatory synapses. Our results add evidence for the diversity of ethanol's effects and mechanisms of action on synaptic transmission in different brain structures, and even in the same brain area (visual cortex) in different species, rats vs mice.