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The role of valence encoding amygdala ensembles in avoidance behavior

Award Number: R00DA062328
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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The role of valence encoding amygdala ensembles in avoidance behavior - PROJECT SUMMARY The ability of an organism to rapidly and accurately assess whether an environmental stimulus is worth approaching or avoiding, also known as valence, is critical to survival. One brain region necessary for this computation is the basolateral amygdala (BLA), which contains discrete ensembles of anatomically intermixed excitatory principal neurons that respond selectively to either positive- and negative-valence stimuli. Recently, I demonstrated that multiphoton activation of these activity defined valence ensembles was sufficient to bias valence-specific behavioral output via mutual ensemble inhibition. However, how this inhibition is generated and its relevance to avoidance behavior is not known. In this proposal, I first aim to determine how functional antagonism of valence-selective ensembles is generated (Aim 1: K99) using chronically implanted microprisms to record the simultaneous activity of both GABAergic and glutamatergic principal neurons during valence stimulus testing. After mapping activity, I will perform microcircuit mapping using multiphoton activation of individual parvalbumin-expressing (PV) interneurons to establish the rules that govern their valence ensemble connectivity and relevance to valence-specific behavioral output. Next, I will identify how antagonistic valence ensemble activity is modulated during avoidance (Aim 2: K99). Using two-photon GRIN lens imaging and a novel specialized conversion adapter allowing for image registration between both freely moving 1-photon calcium and 2-photon imaging, I will determine how valence ensembles in the BLA are modulated avoidance. I will then generate computational models to identify specific ensembles responsible for encoding avoidance behavior. I will then target these ensembles for multiphoton inhibition to assess their role in producing avoidance behavior. Finally, I will isolate how norepinephrine (NE) release from the locus coeruleus (LC) alters BLA ensemble activity through gain control to promote avoidance behavior (Aim 3: R00) to identify the endogenous signal that is governing BLA ensemble recruitment to promote avoidance behavior. Using combined optogenetics and fiber photometry I will first measure NE release in the BLA following an acute stressor, and compare this to release evoked by optogenetic activation of LC terminals in BLA. I will then conduct 1-photon calcium imaging, avoidance behavioral assays, pharmacology, and graph theory analyses, I will evaluate whether activation of LC terminals in BLA alters ensemble activity via β2-adrenergic receptors (ARs). The training received following the completion of this proposal will facilitate my transition to running an independent laboratory focused on neuromodulation of avoidance circuits.


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: 2026 ( Subtotal = $248,999 )
2026	2026	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Drug Use and Addiction Research Programs	000	3	6/25/2026	EXTENSION WITH OR WITHOUT FUNDS	$248,999
														Subtotal = $248,999

Grand Total All Awards = $248,999

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The role of valence encoding amygdala ensembles in avoidance behavior

Award Number: R00DA062328

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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