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mPFC Regulation of VTA Dopamine and GABA Neuronal Activity During Flexible Updating of Appetitive and Aversive Associations

Award Number: F32DA060070
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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mPFC Regulation of VTA Dopamine and GABA Neuronal Activity During Flexible Updating of Appetitive and Aversive Associations - Project Summary/Abstract In order to efficiently traverse an environment, one must learn to distinguish among cues that predict outcomes of different modalities, such as an appetitive reward or an aversive shock. In a dynamic environment where cues predicting rewarding or aversive outcomes unexpectedly change, it is adaptive to flexibly update behavioral responding while retaining the ability to recall previous associations. Impairments in the ability to appropriately respond to cues according to the outcome are evident in a number of psychiatric disorders. The overarching aim of my postdoctoral training is to better understand the neural circuitry responsible for updating previously learned cue-outcome associations. A large literature has implicated the ventral tegmental area (VTA) in the initial learning of appetitive and aversive associations. Both dopamine and γ-aminobutyric acid (GABA) neurons in the VTA are involved individually or cooperatively in different aspects of appetitive and aversive learning. After initial learning, I hypothesize that flexible responding to changes in outcome contingencies is modulated by the medial prefrontal cortex (mPFC) projections to the VTA in a valence-specific manner. To behaviorally quantify initial learning as well as updating cue-outcome associations, I will use a flexible contingency learning (FCL) task in which three distinct cues are paired with either an appetitive outcome (sugar pellet reward), an aversive outcome (mild foot shock), or no outcome. After learning, the appetitive and aversive outcomes reverse such that the cue previously paired with a shock will instead precede reward delivery and vice versa. I will be trained in fiber photometry recordings from VTA dopamine and GABA neurons as well as chemogenetic manipulation of the mPFC-VTA pathway to test whether the mPFC regulates flexible updating in a valence-specific manner. Regardless of the outcome, the proposed work will increase our understanding of the flexible updating of behavioral responding when outcome contingencies change.


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 = $74,284 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Drug Use and Addiction Research Programs	000	2	1/15/2025	NON-COMPETING CONTINUATION	$74,284
														Subtotal = $74,284

Issue Date FY: 2023 ( Subtotal = $69,080 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Drug Use and Addiction Research Programs	000	1	8/9/2023	NEW	$69,080
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Drug Use and Addiction Research Programs	001	1	8/9/2023	NEW	$0
														Subtotal = $69,080

Grand Total All Awards = $143,364

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mPFC Regulation of VTA Dopamine and GABA Neuronal Activity During Flexible Updating of Appetitive and Aversive Associations

Award Number: F32DA060070

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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