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bioRxiv · 10.1101/337097

Chronic intermittent ethanol exposure selectively increases synaptic excitability in the ventral domain of the rat hippocampus

Ewin, S. E.·Morgan, J. W.·Nierre, F.·McMullen, N. P.·Barth, S. H.·Almonte, A. G.·Raab-Graham, K. F.·Weiner, J. L.
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Abstract

Many studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety-and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. To that end, we examined the effects of the chronic intermittent ethanol vapor exposure (CIE) model of AUD on dHC and vHC synaptic excitability. Adult male Long-Evans rats were exposed to CIE or air for 10 days (12 hrs/day; targeting blood ethanol levels of 175-225 mg%) and recordings were made 24 hours into withdrawal. As expected, this protocol increased anxiety-like behaviors on the elevated plus-maze. Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, was dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal.\n\nHighlightsChronic intermittent ethanol exposure produces robust increases in anxiety-like behavior in male Long Evans rats.\nChronic intermittent ethanol exposure increases synaptic excitability in the ventral, but not the dorsal, domain of the hippocampus.\nThese changes in excitability are associated with alterations in synaptoneurosomal expression of small conductance calcium-activated potassium channels and the GluA2 AMPA receptor subunit that are also restricted to the ventral hippocampus.

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Ewin, S. E., Morgan, J. W., Nierre, F., McMullen, N. P., Barth, S. H., Almonte, A. G., Raab-Graham, K. F., Weiner, J. L.. 2018-06-03. Chronic intermittent ethanol exposure selectively increases synaptic excitability in the ventral domain of the rat hippocampus. https://doi.org/10.1101/337097

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