Leptin-mediated control of sociosexual behaviour

• Applicant: Dr. Anne Petzold
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555348169

Depression is one of the leading causes of years lived with disability and its incidence is set to rise in the next decades bar new interventions that improve or even prevent the development of depressive symptoms. In depressive patients, levels of leptin - an adipose tissue-derived hormone – are dysregulated. While leptin treatment is a newly emerging strategy to improve emotional and social functioning in depression, the mechanisms of leptin-mediated control of non-nutritional behaviours are unknown, limiting its utility as an antidepressant. Its dedicated study has been hampered by (1) our lack of knowledge of candidate leptin-sensitive neuronal populations in the brain, and (2) technical challenges to measure the activity of leptin-sensitive populations across states in freely behaving animals. In my postdoctoral work, I pioneered the application of single-cell calcium imaging with GRIN lenses and miniaturized endoscopes in deep brain regions. I used this approach to perform unprecedented longitudinal recordings of the neuronal activity in individual, leptin-sensitive neurons in freely moving and interacting mice, and combined these recordings with optogenetic neural activity manipulations. I thereby identified leptin-sensitive neuronal populations located in the lateral hypothalamus as a promising potential substrate for leptin-mediated control of sociosexual behaviour. In this project, we will identify and characterize the neuronal substrates and state-dependent mechanisms of leptin-mediated, sex-specific neuronal control of social and sexual behaviour in health and disease. First, my group will identify the neuronal circuitry for leptin-mediated regulation of sociosexual behaviour and provide the first map of a sex-specific leptin-sensitive neural circuitry on an anatomical, histological, and functional level. Second, we will characterize the interaction of leptin-sensitive circuits with sex and estrous cycle stage to achieve a comprehensive understanding of the fundamental contribution of leptin signaling for the sex-specific regulation of sociosexual behaviour under normal conditions. Third, we will test the utility of leptin for the improvement of social and sexual motivation in a depression model. Ours will be the first study to test whether an enhancement of leptin signaling improves sociosexual functioning in health and disease, in a sex and estrus cycle-specific manner. Our findings will provide essential insights of potential therapeutic utility for the treatment of sociosexual symptoms in depressive disorders.

• DFG Programme: Emmy Noether Independent Junior Research Groups
• Major Instrumentation: Fiber photometry system ; Microendosope
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)