Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Sicher, Avery; Starnes, William D.; Griffith, Keith R; Dao, Nigel C.; Smith, Grace C; Brockway, Dakota F.; Crowley, Nicole A.

doi:10.1016/j.neuropharm.2023.109561

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…However, mGlu 5 receptors are one of the most widely expressed GPCRs but most cell types do not express overt physiological sex differences. Even in the closely related somatostatin-expressing interneurons, we and others found minimal evidence for sex differences in basal properties [42,89–91] or in mGlu receptor signaling [29,92]. These findings beg the question, what factors make PV-INs sensitive to sex-dependent mGlu receptor signaling?…”

Section: Discussionmentioning

confidence: 55%

Parvalbumin interneuron mGlu₅receptors govern sex differences in prefrontal cortex physiology and binge drinking

Fabian,

Jordan,

Cole

et al. 2023

Preprint

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Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. Activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu1and mGlu5metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5-/-mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol’s stimulant properties. Importantly, these studies identify mGlu1and mGlu5receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant for alcohol use.

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Section: Discussionmentioning

confidence: 55%

Parvalbumin interneuron mGlu₅receptors govern sex differences in prefrontal cortex physiology and binge drinking

Fabian,

Jordan,

Cole

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Electrophysiology was conducted between 9-12 months of age (+/- 2 weeks; corresponding to about 6 months following the cessation of alcohol consumption) similar to our previously published work (Brockway et al, 2023; Sicher et al, 2023). Mice were exposed to an isoflurane chamber for deep anesthetization, the brain was quickly extracted and processed according to the N-methyl-D-glucamine (NMDG) protective recovery method (Ting et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling in Mice

Smith,

Griffith,

Sicher

et al. 2024

Preprint

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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.

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“…Rheobase and VI protocols were conducted consistent with previously published methods from our lab. 56 The rheobase protocol consisted of 4 sequential ramps, each injecting 120 pA of current, and each subsequent ramp stepping by 100 pA. Ramps lasted 1000 ms, and the protocol was stopped after the ramp during which the cell fired an action potential.…”

Section: Methodsmentioning

confidence: 99%

Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Cited by 11 publications

References 42 publications

Parvalbumin interneuron mGlu₅receptors govern sex differences in prefrontal cortex physiology and binge drinking

Parvalbumin interneuron mGlu₅receptors govern sex differences in prefrontal cortex physiology and binge drinking

Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling in Mice

Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior

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Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Cited by 11 publications

References 42 publications

Parvalbumin interneuron mGlu5receptors govern sex differences in prefrontal cortex physiology and binge drinking

Parvalbumin interneuron mGlu5receptors govern sex differences in prefrontal cortex physiology and binge drinking

Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling in Mice

Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior

Contact Info

Product

Resources

About

Parvalbumin interneuron mGlu₅receptors govern sex differences in prefrontal cortex physiology and binge drinking

Parvalbumin interneuron mGlu₅receptors govern sex differences in prefrontal cortex physiology and binge drinking