Ethanol experience elicits circuit specific adaptations of ventral hippocampal-accumbens glutamatergic signaling

Kircher, Daniel M.
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The purpose of this study was to determine the effects of ethanol exposure and consumption on the expression of plasticity of D1 dopamine receptor expressing (D1R) medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell receiving glutamatergic input solely from the ventral hippocampus (vHipp). Drd1a-tdTomato mice on a C57BL/6J background were injected bilaterally in the vHipp with a viral vector in order to express channelrhodopsin (ChR2) in vHipp terminals that synapse onto shell D1R-MSNs. Blue LED light stimulation was used to selectively depolarize ChR2 expressing vHipp terminals in the NAc shell, resulting in light-evoked EPSCs originating from vHipp. In voltage clamp experiments, we found that an induction protocol pairing 1 Hz blue light stimulation with postsynaptic membrane depolarization produced LTD in the vHipp to NAc circuit that is NMDA receptor dependent. In this study we found acute application of ethanol in vitro uniquely alters plasticity in the vHipp to NAc circuit. Low to moderate intoxicating concentration of ethanol blocked light evoked LTD expression which is in contrast to previous observations. Ethanol consumption in rodents impaired vHipp-Shell plasticity as well as resulted in altered glutamatergic signaling, and the insertion of Ca2+ permeable AMPA receptors (CPARs) D1R-MSNs post synaptic membranes. These findings suggest that the vHipp to NAc circuit is highly sensitive to ethanol treatment and may constitute a critical neuroadaptation that leads to the expression of ethanol dependence.