Discovery of two distinct subpopulations of ntsr1-expressing neurons in the substantia nigra pars compacta

Feeding behavior and energy balance are largely influenced by dopamine (DA) neuronal activity. The neurotensin (Nts) system is also largely linked to feeding and weight loss behaviors. Dopaminergic neurons in the substantia nigra pars compacta (SNc) are responsible for locomotor activity, motivation and habit forming. Modulating Nts and neurotensin receptor 1 (NtsR1) has been linked to reduce feeding and increase locomotor activity however, the mechanisms and brain regions responsible for these behaviors are yet to be discovered. In the SNc, I have found NtsR1 expressing neurons, though not all NtsR1 neurons in the SNc are dopaminergic. This was confirmed using three complementary approaches: genetic reporter mice, RNAScope in situ hybridization, and viral recombinase tracing to define the cellular identity of NtsR1-expressing neurons in the SNc. I hypothesize that NtsR1 is expressed not only in dopaminergic neurons but also in a distinct non-dopaminergic subpopulation within the SNc and these two distinct populations contribute to weight loss behaviors in different ways. While SNc DA neurons are well studied in movement and locomotor function, their involvement in feeding regulation has not been characterized. Moreover, the specific role of SNc^NtsR1-only neurons remains entirely unexplored. This study aims to determine how chemogenetic activation of SNc^NtsR1+DA and SNc^NtsR1-only neurons influences feeding, movement, and body weight. Findings will clarify how distinct SNc NtsR1 neuronal populations contribute to feeding and movement control, offering insight into the neural basis of obesity-related behavioral changes. Understanding these pathways may inform novel targets for treating metabolic disorders without impairing motor function. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.