Agouti-related peptide (AgRP) neurons in the hypothalamus are key regulators of feeding behaviour and energy balance (1,2) . Emerging evidence indicates that these circuits also influence higher-order cognitive processes through their modulation of hippocampal GABAergic networks (3,4) . Disruptions in such metabolic–cognitive interactions are relevant to neurodegenerative conditions, particularly Alzheimer’s disease (5) . Clarifying these mechanisms requires integrating next-generation neurotechnologies into the field of nutritional neuroscience (6,7) . The aim of this study is to investigate how activation of AgRP neurons modulates hippocampal activity and cognitive performance, thereby elucidating the neural mechanisms linking nutritional state and memory processes. We utilised AgRP-Cre × Vgat-Flp double transgenic mice to examine how AgRP neuronal activity impacts hippocampal function and cognition. Recombinant adeno-associated viral vectors carrying chemogenetic constructs (hM3Dq DREADDs) were injected into the arcuate nucleus to selectively activate AgRP neurons, while calcium sensors (GCaMP6) were introduced into the dentate gyrus. To manipulate neuronal activity, Deschloroclozapine (DCZ) was delivered intraperitoneally following chemogenetic receptor expression. Fluorescent viral tracers were used to visualise AgRP neuronal projections to their downstream targets. In parallel, fibre photometry is being employed during the Novel Object Recognition task to capture calcium dynamics in real time and relate these signals directly to memory performance. Parallel feeding assays were performed to assess the interface between energy balance and cognition. Fibre photometry analyses revealed no statistically significant difference in calcium signal amplitude between the DCZ-treated (AgRP-activated) and saline control groups. However, the DCZ group showed a mild upward trend in mean z-score values, indicating a potentialincrease in hippocampal activity following AgRP neuron activation. Although individual animals exhibited variable signal patterns, some displayed transient increases in calcium fluorescence during object exploration. These findings suggest that AgRP activation may subtly modulate hippocampal network activity, though larger cohorts are required to confirm this effect. While AgRP activation did not elicit a significant change in hippocampal calcium activity, the observed trend points to a possible modulatory link between hypothalamic hunger circuits and hippocampal function. These preliminary results emphasise the importance of integrating chemogenetic and fibre photometry methods to uncover subtle neural mechanisms that couple nutritional state and cognition.
Atar et al. (Fri,) studied this question.
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