Neural Mechanisms of Threat Learning and Avoidance: Adaptive and MaladaptiveBehaviors

This project aims to investigate the roles of a newly identified population of neurons in the supramammillary nucleus (SuM) that are essential for threat learning and avoidance behaviors. These neurons are activated by diverse stressors and may play critical roles in threat conditioning and persistent avoidance. The specific aims of this research are to: (1) elucidate the temporal dynamics and causal roles of these neurons during threat learning, avoidance, and extinction using fiber photometry, optogenetics, and behavioral assays; (2) determine whether these neurons selectively excite neuron populations in the nucleus accumbens (NAc) to promote threat avoidance; and (3) reveal the neural types in SuM and which are recruited during threat learning and sustained avoidance using advanced molecular techniques such as Projection-TAGs, barcoded retrograde viruses, and Act-seq with single nucleus RNA sequencing. By characterizing this novel neural circuitry, the project aims to advance our understanding of active coping mechanisms and contribute to the development of new treatments for stress and anxiety-related disorders by identifying potential therapeutic targets. Project Number: 1R01MH139879-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Aaron Norris | Institution: WASHINGTON UNIVERSITY, SAINT LOUIS, MO | Award Amount: $735,920 | Activity Code: R01 | Study Section: Neurobiology of Motivated Behavior Study Section[NMB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11298332