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bioRxiv · 10.1101/2024.04.03.587955

MODERATE ALCOHOL CONSUMPTION INDUCES LASTING IMPACTS ON PREFRONTAL CORTICAL SIGNALING IN MICE

Abstract

Both alcohol use disorder (AUD) and Alzheimers Disease and Related Dementias (ADRD) appear to include disruption in the balance of excitation and inhibition in the cortex, but their potential interactions are unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons. A profound increase in excitatory events onto layer 2/3 non-pyramidal neurons following alcohol consumption was seen, along with altered intrinsic excitability of pyramidal neurons, which could have a range of effects on Alzheimers Disease progression in humans. These results indicate that moderate voluntary alcohol influences the pre-disease environment in aging and highlight the need for further mechanistic investigation into this risk factor. HIGHLIGHTSO_LIModerate voluntary alcohol consumption leads to disruption of prefrontal cortical signaling at protracted ages in both male and female mice C_LIO_LIExcitatory glutamatergic events onto prelimbic cortex GABAergic neurons, but not pyramidal neurons, are increased 6 months following alcohol exposure C_LIO_LIBoth pyramidal neurons and GABAergic neurons show altered intrinsic excitability 6 months following alcohol exposure C_LI

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Smith, G. C., Griffith, K. R., Sicher, A. R., Brockway, D. F., Proctor, E. A., Crowley, N. A.. 2024-04-05. MODERATE ALCOHOL CONSUMPTION INDUCES LASTING IMPACTS ON PREFRONTAL CORTICAL SIGNALING IN MICE. https://doi.org/10.1101/2024.04.03.587955

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