Study of hypothalamic circuits that regulate metabolism and the endocrine system

Abstract

The hypothalamus is a structure located at the base of the brain, responsible for regulating various visceral functions. Thus, body homeostasis depends on the control of hypothalamic circuits, which are still little known. The hypothalamus regulates the functioning of the body by controlling the expression of motivated behaviors, the autonomic nervous system and finally by regulating the secretion of pituitary hormones. Alterations in the functioning of these hypothalamic circuits may be responsible for the emergence of several metabolic and endocrine diseases. This project aims to study the functioning of hypothalamic circuits responsible for regulating metabolism and the endocrine system. Therefore, a combination of histological and electrophysiological techniques will be used in genetically modified mouse tissues, in order to obtain more information about the neurais networks that make up the hypothalamus. For the plan of this postdoctoral fellowship, the fellow will initially establish in our laboratory the RNAScope technique that allows the identification of the expression of messenger RNAs of interest, in specific neural populations. Concomitantly, we will establish the record of neural activity, through the indirect technique of calcium imaging. We have the necessary equipment to perform this technique and the necessary animal model (LoxP-STOP-LoxP-GCaMP6f; https://www.jax.org/strain/028865) will arrive in our bioterium in october 2021. With this model, we will study how the action of some hormones of interest, such as GH, leptin and others, can affect the influx of intracellular calcium. Finally, in neural populations that respond in the calcium imaging method, we intend to deepen the recording of activity using the whole-cell patch clamp technique. All these techniques will be performed in tissues from genetically modified mice, whose cells of interest express a fluorescent reporter protein, which allows their identification. The cells initially studied are located in hypothalamic nuclei that control metabolism and the neuroendocrine system, including neurons in the periventricular, paraventricular, arcuate and lateral hypothalamic nuclei. Thus, this project will be able to discover new mechanisms and neural circuits related to the control of metabolism and endocrine system. (AU)