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Sunday, November 15, 2009

Acute ethanol exposure elevates muscarinic tone in the septohippocampal system



The septohippocampal system has been implicated in the cognitive deficits associated with ethanol consumption, but the cellular basis of ethanol action awaits full elucidation. In the MS/DB, a muscarinic tone, reflective of firing activity of resident cholinergic neurons, regulates that of their non-cholinergic, putatively GABAergic, counterparts.

Here we tested the hypothesis that ethanol alters this muscarinic tone.

The spontaneous firing activity of cholinergic and non-cholinergic MS/DB neurons were monitored in acute MS/DB slices from C57Bl/6 mice.

Exposing the entire slice to ethanol increased firing in both cholinergic and non-cholinergic neurons. However, applying ethanol focally to individual MS/DB neurons increased firing only in cholinergic neurons. The differential outcome suggested different mechanisms of ethanol action on cholinergic and non-cholinergic neurons. Indeed, with bath-perfused ethanol, the muscarinic antagonist methyl scopolamine prevented the increase in firing in non-cholinergic, but not cholinergic, MS/DB neurons.

Thus, the effect on non-cholinergic neuronal firing was secondary to ethanol's direct action of acutely increasing muscarinic tone.

We propose that the acute ethanol-induced elevation of muscarinic tone in the MS/DB contributes to the altered net flow of neuronal activity in the septohippocampal system that underlies compromised cognitive function.

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Request Reprint E-Mail: hermes.yeh@dartmouth.edu

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