Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling
Restricted (Penn State Only)
- Author:
- Smith, Grace
- Graduate Program:
- Biomedical Engineering
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- February 19, 2024
- Committee Members:
- Nikki Crowley, Thesis Advisor/Co-Advisor
Patrick James Drew, Committee Member
Yuguo Lei, Professor in Charge/Director of Graduate Studies
Elizabeth Anne Proctor, Committee Member - Keywords:
- prefrontal cortex
alcohol
binge drinking
Alzheimer's Disease
electrophysiology - Abstract:
- Both alcohol use disorder and Alzheimer's Disease appear to include disruption in the balance of excitation and inhibition, which is critical for maintaining information processing in the cortex. Here, I examined the effect of binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on pyramidal (excitatory) and non-pyramidal (inhibitory) neurons in the prelimbic cortex following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on intrinsic excitability in pyramidal neurons and on spontaneous vesicle release onto non-pyramidal neurons. These changes may be due to a homeostatic regulation of activity in the prolonged period following alcohol exposure that results in overcompensation of pyramidal intrinsic excitability and spontaneous excitatory signaling onto non-pyramidal neurons. The increase in excitatory events onto non-pyramidal neurons following alcohol consumption could have a range of effects on Alzheimer’s Disease progression in humans. First, the increase of excitation onto inhibitory non-pyramidal neurons could result in greater inhibitory firing and confer a protective effect against Alzheimer’s Disease hyperexcitability. Alternatively, the increase in excitatory input could result in greater synchrony of inhibitory signaling, decreasing entropy and worsening Alzheimer’s Disease progression. Finally, alcohol exposure doubling the number of excitatory events onto non-pyramidal neurons may result in excitotoxicity and cell death, which would significantly worsen Alzheimer’s Disease progression, as there is already significant loss of interneurons. In layer 2/3 of the murine prelimbic cortex, binge alcohol consumption alters intrinsic excitability of pyramidal neurons and increases spontaneous excitatory release onto non-pyramidal neurons, even after prolonged abstinence from alcohol, indicating that alcohol influences the pre-disease environment in aging.