ABSTRACT
Both alcohol use disorder (AUD) and Alzheimer’s 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 Alzheimer’s 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.
HIGHLIGHTS
Moderate voluntary alcohol consumption leads to disruption of prefrontal cortical signaling at protracted ages in both male and female mice
Excitatory glutamatergic events onto prelimbic cortex GABAergic neurons, but not pyramidal neurons, are increased 6 months following alcohol exposure
Both pyramidal neurons and GABAergic neurons show altered intrinsic excitability 6 months following alcohol exposure
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Declarations of interest: none
ABBREVIATIONS
- aCSF
- artificial cerebrospinal fluid
- AP
- action potential
- AUD
- alcohol use disorder
- ADRD
- Alzheimer’s Disease and Related Dementias
- DID
- Drinking-in-the-Dark
- E/I
- excitatory/inhibitory
- EtOH
- ethanol
- fAHP
- fast afterhyperpolarization
- NMDG
- N-methyl-D-glucamine
- PL
- prelimbic
- RMP
- resting membrane potential
- sEPSC
- spontaneous excitatory postsynaptic current
- sIPSC
- spontaneous inhibitory postsynaptic current
- VI
- current injection