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Neurobiological responses of somatostatin neuronal circuits to environmental light disruptions during pubertal development

Award Number: R01AT013234
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2029

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Neurobiological responses of somatostatin neuronal circuits to environmental light disruptions during pubertal development - Over 80% of the world's population lives under light-polluted skies, with indoor light exposure rising due to factors like electronic devices. Exposure to altered light environments induces circadian disruptions, leading to adverse neurophysiological and behavioral changes including anxiety disorders. Adolescents, who often have altered sleep patterns and extensive electronic device use, are particularly vulnerable to circadian disruptions. However, the neurobiological effects of light interventions on brain circuits and behaviors during pubertal development are understudied. Mammalian light perception involves specialized retinal cells that communicate light information to various brain regions, including the medial amygdala (MeA), which processes environmental cues to control emotional responses. Our long-term goal is to understand how the MeA circuit adapts to light environments during adolescence, and whether light interventions can enhance resilience and prevent anxiety disorders induced by circadian disruptions. We recently demonstrated that altered light environments during adolescence increased avoidance behaviors, increased somatostatin neuronal activity and decreased inward-rectifying potassium channels expression in the MeA. MeA neurons in turn project to the bed nucleus of the stria terminalis (BNST), a brain region involved in avoidance responses. Given the key role of somatostatin signaling in the amygdala in regulating affective behaviors, we seek to characterize the mechanism by which somatostatin neurons in the MeA adapt to light environments to regulate emotional responses and promote resilience. We will test the general hypothesis that somatostatin neurons in the MeA act as a key regulator, capable of adjusting to light environments to influence adaptive responses (resilience). Three Specific Aims are proposed to functionally dissect the role of somatostatin neurons in mediating lightinduced adaptive behaviors: In Aim 1, we will investigate whether somatostatin neurons in the MeA are required for light-induced avoidance behavior through chemogenetic manipulations and cell-type-specific ablation of somatostatin expression in adolescent mice exposed to chronic light cycles disruption. In Aim 2, we will establish the role of inward-rectifying potassium channel in regulating light-induced increase of somatostatin neuronal activity in the MeA regulating avoidance behaviors. In Aim 3, we will study MeA somatostatin cells downstream projections to uncover the circuits mediating light-induced avoidance behaviors by employing in vivo fiber photometry for neuronal activity and somatostatin release recording in the BNST of adolescent mice exposed to chronic light cycle disruption. We will also use optogenetic approach to inhibit MeA somatostatin synapsis terminals into the BNST while testing adolescent mice for light-induced avoidance behaviors. By integrating a diverse set of cutting-edge methodologies, this project will advance our understanding of the adaptive mechanisms of the MeA somatostatin circuit in response to light environments. Our goal is to provide pre-clinical data to develop safe light interventions that enhance resilience and prevent affective disorders in adolescents experiencing circadian disruptions.


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 = $517,666 )
2026	2026	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Research and Training in Complementary and Integrative Health	000	2	3/23/2026	NON-COMPETING CONTINUATION	$517,666
														Subtotal = $517,666

Issue Date FY: 2025 ( Subtotal = $507,427 )
2025	2025	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Research and Training in Complementary and Integrative Health	000	1	3/31/2025	NEW	$507,427
														Subtotal = $507,427

Grand Total All Awards = $1,025,093

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Neurobiological responses of somatostatin neuronal circuits to environmental light disruptions during pubertal development

Award Number: R01AT013234

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2029

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