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Hippocampal dopamine signaling and food-related memory: implications for obesity

Award Number: F31DK142526
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/15/2025
PERIOD OF PERFORMANCE END DATE: 09/14/2028

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Hippocampal dopamine signaling and food-related memory: implications for obesity - Project Summary/ Abstract Dopamine (DA) is a neurotransmitter associated with reward and reward-prediction based learning9. One type of rewarding stimulus is the consumption of food which provides both orosensory and post-ingestive positive feedback10; 11. In a modern society where food is both plentiful and more energetically dense, these systems may also be involved in the etiology of obesity and overeating12; 13. In fact, research in human subjects with obesity and obese rodent models has found that dopaminergic (DAergic) signaling machinery is dysregulated compared to healthy subjects in key reward processing centers such as the nucleus accumbens in the ventral striatum (ACB)14; 15; 16. The hippocampus (HPC), a brain region associated with memory function, has also been implicated in the higher-order control of food intake17; 18. For example, humans with bilateral HPC damage will eat multiple meals in rapid succession yet report little to no change in hunger or satiety11. Further, primed verbal recall of a previous meal can reduce the consumption of a subsequent snack19; 20. While not as widely studied as the midbrain DA pathway, the HPC also receives DAergic innervation from VTA neurons associated with reward21; 22; 23. HPC neurons also express both major classes of DA receptors rendering them able to respond to DA24; 25; 26. DA receptors have been shown to influence the synaptic plasticity and firing patterns of HPC neurons, properties which are widely considered the molecular substrates for memory formation26; 27. Human PET scan data revealed that DA is indeed released in the HPC following a palatable meal, and in mice, manipulating the activity of DA receptor-expressing HPC neurons influences food intake28; 29. Together, these data suggest that meal-induced DA signaling in the HPC may influence future food intake, and that dysregulation of this system may contribute to obesity. We hypothesize that elevated dHPC DA signaling upon eating serves to encode an episodic memory of consuming a meal. Preliminary data presented herein reveal that HPC targeted DA type 2 receptor (D2R) but not D1R blockade impairs meal location memory in male rats. Aim 1 experiments will investigate if this phenotype is specific to food-specific memories, and if manipulation of these receptors influences food intake. Other preliminary findings using in vivo DA-sensing molecules also show that HPC DA is elevated in a post- meal state. These results were found using a mixed nutrient meal, and the proposed work will aim to parse these HPC DA responses to isolated macronutrients, as well as to post-ingestive versus orosensory responses to nutrients. Finally, Aim 3 seeks to build on previous findings in the lab revealing that diet induced obesity (DIO) rat models have impaired meal location memory. We hypothesize that these memory deficits may arise from aberrant expression of DAergic machinery in the HPC which may result in a blunted post-meal DA release. Overall, improved understanding of the mechanisms underlying HPC DA signaling and the higher-order control of food intake can elucidate the role of food reward and overeating behaviors associated with obesity.


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 = $49,538 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	6/17/2025	NEW	$0
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	9/12/2025	NEW	$0
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/17/2025	NEW	$49,538
														Subtotal = $49,538

Grand Total All Awards = $49,538

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Hippocampal dopamine signaling and food-related memory: implications for obesity

Award Number: F31DK142526

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/15/2025

PERIOD OF PERFORMANCE END DATE: 09/14/2028

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