Unraveling hippocampal networks related to food memories

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Our group at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is uniquely positioned to investigate how hippocampal and cortical networks encode and retrieve food-associated memories, and how these systems interact with hypothalamic and mesolimbic circuits to guide feeding behavior. Using rodent models, the lab employs in vivo calcium imaging, optogenetics, chemogenetics, and activity-dependent tagging (e.g., TRAP systems) to define the ensembles within the hippocampus, prefrontal cortex, and amygdala that support episodic and contextual memory of food cues. These studies advance the field of cognitive and systems neuroscience while directly addressing NIH research priorities in understanding the neural substrates of learning, memory, and motivation as they relate to obesity, disordered eating, and metabolic disease. A critical extension of this work is to determine how anti-obesity therapeutics such as semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, alter memory-guided feeding processes. GLP-1 receptor signaling is known to act in the hypothalamus and hindbrain to promote satiety, but accumulating evidence indicates that it also influences hippocampal and corticolimbic networks to reduce food cue reactivity and conditioned reinforcement. By combining pharmacological interventions with circuit-level readouts, the lab can test whether semaglutide modifies the stability or retrieval of food-related memory traces, suppresses hippocampal-driven cue reactivity, or recalibrates communication between memory and reward systems. These efforts align with NIH scientific programs in the gut–brain axis, neuroendocrinology, and therapeutic mechanism of action and address disease areas including obesity, type 2 diabetes, and binge eating disorder. Through this integrative approach, the Krashes laboratory contributes to a broader scientific mission of the NIH by connecting basic neural circuit analysis with translational pharmacology. By elucidating how hippocampal memory systems bias feeding decisions, and how GLP-1–based therapies reshape these associations, this research identifies mechanistic nodes that could be targeted to improve treatment of obesity and related metabolic disorders. These studies also inform the development of next-generation interventions that not only blunt appetite and food consumption but also modify maladaptive food memories and cue-driven relapse, ultimately reducing the public health burden of metabolic disease.