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Principal Investigator: Melanie M Pina
Organization: UNIVERSITY OF MARYLAND BALTIMORE
Fiscal Year: 2024
Award: $76,809
Funding agency: National Institute on Alcohol Abuse and Alcoholism
Project Summary
Repeated episodes of binge alcohol drinking dysregulate serotonin (5-hydroxytryptamine, 5-HT) systems
throughout the brain, which may place an individual at greater risk of developing an alcohol use disorder
(AUD). The orbitofrontal cortex (OFC) is one site of 5-HT innervation that has been shown to undergo plastic
changes after heavy alcohol intake. Previous work has indicated that chronic alcohol exposure disrupts 5-HT
signaling in the OFC, leading to a loss of its inhibitory control in this region. Preliminary findings from the
parent R00 grant show that binge-like patterns of alcohol intake alter OFC activity across multiple species
and produce profound impairments in 5-HT1A receptor signaling in this region. However, this work from our
group and others has focused primarily on pyramidal neurons when evaluating alcohol’s impact on the OFC.
Of note, the OFC has a complex microcircuitry that contains interspersed GABA interneurons (INs) that fine-
tune the activity patterns of pyramidal cells and other IN populations. These cortical INs, which can be
broadly classified based on their expression of parvalbumin (PV) or somatostatin (SST), appear to serve
distinct roles in the coordination of OFC activity. Given the complex microcircuitry of the OFC and interplay
between its mixed neuronal populations, it will be informative to examine the broader cellular network in
which alcohol-induced adaptations may occur. At present, the impact of binge intake on OFC PV-INs and
SST-INs remains unknown. The project proposed by the supplement candidate will address this knowledge
gap through a series of experiments that evaluate plasticity induced by binge-like alcohol drinking in PV-INs
and SST-INs and its effect on 5-HT signaling in these cell populations. In Aim 1, the candidate will perform
whole-cell patch clamp electrophysiology recordings in the OFC of PV and SST reporter mice following
repeated cycles of binge alcohol intake. Specifically, the candidate will examine changes in excitability,
synaptic transmission, and 5-HT signaling in these genetically defined IN populations. In Aim 2, the applicant
will use fluorescence in situ hybridization to measure the effect of binge alcohol on 5-HT receptor mRNA
expression levels in OFC PV and SST INs. In addition to yielding novel information, this supplement award
will add to the candidate’s existing scientific toolkit by allowing him to receive training in more advanced
cellular and molecular techniques, including ex vivo electrophysiology, fluorescence in situ hybridization, and
confocal microscopy. Beyond technical training, this diversity supplement will provide the candidate with
professional development opportunities and an individualized mentoring plan that will support his graduate
work and foster his career progression. Combined, the proposed project and supplemental training will
enhance the candidate’s graduate research experience and facilitate his successful transition to the next
phase of his career as a postdoctoral fellow.
Terms: <4-Aminobutanoic Acid><4-Aminobutyric Acid><4-amino-butanoic acid><5-HT><5-HT Receptors><5-HT(1A) Receptor><5-HT1A Receptor><5-Hydroxytryptamine><5-Hydroxytryptamine 1A Receptor><5-Hydroxytryptamine Receptors><5HT><Alcohol Chemical Class><Alcohol Drinking><Alcohol consumption><Alcohols><Aminalon><Aminalone><Anxiety><Award><Brain><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Chronic><Classification><Complex><Confocal Microscopy><Connector Neuron><Cyclic Somatostatin><Death Rate><Development><Dysfunction><Electrophysiology><Electrophysiology (science)><Encephalon><Enteramine><EtOH drinking><EtOH use><FISH Technic><FISH Technique><FISH analysis><FISH assay><Fluorescence In Situ Hybridization><Fluorescent in Situ Hybridization><Fostering><Functional disorder><Future><GABA><Grant><Growth Hormone Inhibiting Factors><Growth Hormone-Inhibiting Hormone><Health><Hippophaine><Impairment><Individual><Intake><Intercalary Neuron><Intercalated Neurons><Interneurons><Internuncial Cell><Internuncial Neuron><Intracellular Communication and Signaling><Knowledge><Measures><Mental Depression><Mentors><Mice><Mice Mammals><Molecular><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neural Transmission><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Outcome><Parents><Parvalbumins><Pattern><Phase><Physiopathology><Population><Postdoc><Postdoctoral Fellow><Public Health><Pyramidal Cells><Pyramidal neuron><Receptor Signaling><Reporter><Research><Research Associate><Risk><Role><SRIH><SRIH-14><Series><Serotonin><Serotonin 1A Receptor><Serotonin Receptor 5-HT1A><Signal Transduction><Signal Transduction Systems><Signaling><Site><Somatostatin><Somatostatin-14><Somatotropin Release Inhibiting Factors><Somatotropin Release-Inhibiting Hormone><Synaptic Transmission><System><Systematics><Techniques><Training><Work><alcohol exposed><alcohol exposure><alcohol ingestion><alcohol intake><alcohol product use><alcohol use><alcohol use disorder><alcoholic beverage consumption><alcoholic drink intake><binge alcohol consumption><binge drinking><biological signal transduction><career><depression><developmental><electrophysiological><episodic drinking><ethanol consumption><ethanol drinking><ethanol exposed><ethanol exposure><ethanol ingestion><ethanol intake><ethanol product use><ethanol use><ethanol use disorder><experience><experiment><experimental research><experimental study><experiments><exposed to alcohol><exposed to ethanol><exposure to alcohol><exposure to ethanol><gamma-Aminobutyric Acid><growth hormone release inhibiting factor><hippocampal pyramidal neuron><innervation><mRNA Expression><mortality rate><mortality ratio><nerve supply><neural circuit><neural circuitry><neurocircuitry><neuronal><novel><parent><patch clamp><pathophysiology><post-doc><post-doctoral><post-doctoral trainee><research associates><serotonin receptor><social role><synaptic circuit><synaptic circuitry><therapeutically effective><treatment strategy><γ-Aminobutyric Acid>