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MERFISH data from the murine hypothalamus in health and under induced sickness states

Moffitt, Jeffrey12; Wong, Bertrand12; Dulac, Catherine34; Sullivan, Zuri3

Published Dec 24, 2025 on Dryad. https://doi.org/10.5061/dryad.v6wwpzh98

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Abstract

In natural environments, animals encounter diverse pathogens that engage specific peripheral host defense programs and elicit sickness behavior – a set of stereotyped physiological and behavioral changes thought to promote host fitness. So far, most studies have relied on one or few mouse models of infection, limiting insights into pathogen-specific neuroimmune interactions that generate sickness.

We hypothesized that different pathogens may elicit distinct sickness states and engage various brain circuits. Using different models of infection and inflammation representing bacterial, viral, allergic, parasitic and colitis conditions, we assessed sickness across scales: organismal – behavior and physiology; cellular – brain-wide neural activity; and molecular – single-cell in situ transcriptomics in the hypothalamus, associated with social and homeostatic functions affected during sickness. Remarkably, immune challenges each elicited unique repertoires of changes across all scales. Our findings reveal specific pathogen-specific sickness states encoded by the brain across scales, thereby broadening our understanding of how infections make us sick.

This repository contains all MERFISH-related data associated with these studies.