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Basolateral amygdala to ventral subiculum network plasticity in alcohol dependent male and female rats

Award Number: K01AA030081
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Basolateral amygdala to ventral subiculum network plasticity in alcohol dependent male and female rats - Project Summary/Abstract Aside from exploring highly relevant scientific questions, the goal of this K01 extends to providing the candidate with mentored training to facilitate her transition to an independent investigator. This encompasses the acquisition of new, sophisticated state-of-the-art techniques as well as career development with the ultimate aim of providing the candidate with a multidisciplinary toolkit to study alcohol use disorder and enhanced mentoring/training skills to relay her expertise to the next generation of mentees interested in alcohol research. Under the mentorship of Dr. Weiner, the candidate will explore the role of posterior basolateral amygdala (BLA) inputs to the ventral subiculum (vSub) of the ventral hippocampus in alcohol dependent male and female rats. Specific Aim 1 of this project will focus on the circuitry and neuroadaptations of pBLA-vSub circuits using the well-validated chronic intermittent ethanol exposure (CIE) paradigm. Based on preliminary findings and growing evidence that the pBLA plays a central role in mediating affective behavior and alcohol drinking-related behaviors, we advance the working hypothesis that CIE initially increases pBLA-vSub excitability in males but that a disproportionate strengthening of inhibitory elements of this circuitry initially protects females from this maladaptive change. However, we predict that this protective effect is either lost or overcome after a longer CIE exposure, leading to similar levels of network excitability and anxiety-like behavior in both sexes. These experiments will focus on two novel inhibitory pBLA-vSub projections that we have begun to characterize, including a monosynaptic GABAergic projection from the pBLA onto vSub glutamatergic neurons. Experiments, using ex vivo optogenetics, and fiber photometry will examine the integrated functional plasticity of glutamatergic and GABAeregic synapses within these pBLA-vSub circuits. To further establish the cellular identity and distribution pattern within the BLA of a novel monosynaptic GABAergic projection neuron population of male and female rats, we will use FISH RNAScope. Additional chemogenetic experiments will then test whether CIE-dependent pBLA-vSub adaptations of synaptic communication (hypoexcitability or hyperexcitability) play a causal role in the anxiety-like phenotypes that emerge during withdrawal from CIE. Together, these findings will significantly advance our understanding of the neural mechanisms responsible for the negative affective symptoms associated with alcohol withdrawal and potentially shed light on novel neural substrates for the development of better treatments for alcohol use disorder.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $142,646 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Alcohol Research Programs	000	4	5/8/2025	NON-COMPETING CONTINUATION	$142,646
														Subtotal = $142,646

Issue Date FY: 2024 ( Subtotal = $142,646 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Alcohol Research Programs	000	3	3/22/2024	NON-COMPETING CONTINUATION	$142,646
														Subtotal = $142,646

Issue Date FY: 2023 ( Subtotal = $142,646 )
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Alcohol Research Programs	000	2	3/18/2023	NON-COMPETING CONTINUATION	$142,646
														Subtotal = $142,646

Issue Date FY: 2022 ( Subtotal = $142,646 )
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Alcohol Research Programs	000	1	3/24/2022	NEW	$142,646
														Subtotal = $142,646

Grand Total All Awards = $570,584

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Basolateral amygdala to ventral subiculum network plasticity in alcohol dependent male and female rats

Award Number: K01AA030081

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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