Lateral hypothalamic galanin neurons are activated by stress and blunt anxiety-like behavior in mice

Joshua Owens-French, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Shi-Bin Li, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Marie Francois, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
R Leigh Townsend, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Mischael Daniel, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Heather Soulier, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Amy Turner, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Luis de Lecea, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Heike Münzberg, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Christopher Morrison, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Emily Qualls-Creekmore, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA. Electronic address: e.qualls-creekmore@wsu.edu.

Abstract

Despite the prevalence of anxiety disorders, the molecular identity of neural circuits underlying anxiety remains unclear. The lateral hypothalamus (LH) is one brain region implicated in the regulation of anxiety, and our recent data found that chemogenetic activation of LH galanin neurons attenuated the stress response to a novel environment as measured by the marble burying test. Thus, we hypothesize that LH galanin neurons may contribute to anxiety-related behavior. We used chemogenetics and fiber photometry to test the ability of LH galanin neurons to influence anxiety and stress-related behavior. Chemogenetic activation of LH galanin neurons significantly decreased anxiety-like behavior in the elevated plus maze, open field test, and light dark test. However, LH galanin activation did not alter restraint stress induced HPA activation or freezing behavior in the fear conditioning paradigm. In vivo calcium monitoring by fiber photometry indicated that LH galanin neurons were activated by anxiogenic and/or stressful stimuli including tail suspension, novel mouse interaction, and predator odor. Further, in a fear conditioning task, calcium transients strongly increased during foot shock, but were not affected by the unconditioned stimulus tone. These data indicate that LH galanin neurons both respond to and modulate anxiety, with no influence on stress induced HPA activation or fear behaviors. Further investigation of LH galanin circuitry and functional mediators of behavioral output may offer a more refined pharmacological target as an alternative to first-line broad pharmacotherapies such as benzodiazepines.