Role of somatostatinergic neurons of the extended amygdala in the control of food intake

• Grant number: 24/21064-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Jose Donato Junior
• Grantee: Stephanie Junqueira dos Reis Rusew
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions, AP.TEM

Abstract

The study of feeding behaviours and energy metabolism is complex and involves many biological systems. In regards of that, the neural control of such parameters comprises different nuclei and brain circuits with a significant contribution from areas such as the extended amygdala (EAc) and the parabrachial nucleus (PBN).The PBN, located at the junction of the midbrain and pons, acts alongside with the nucleus of the solitary tract to transmit visceral and gustatory signals to hunger and satiety centers. Besides its integrative and transmission role the PBN is composed of a highly heterogenous neuronal population, some of which are involved in the control and regulation of feeding behaviours, as is the case of neurons that express the calcitonin gene-related peptide (CGRP), known regulators of satiety circuits.The EAc is a macrostructure composed by the central nucleus of the amygdala (CeA), the bed nucleus of the stria terminalis (BNST), the sublenticular extended amygdala (SLEA) and outer regions of the nucleus accumbens (Nac Shell). CeA and BNST are considered the main components of this macrostructure and are considered heterogenous nuclei, with a diverse neuronal population that are reported to exert different actions over feeding on both physiological and hedonistic situations. Despite being highly heterogenous, both nuclei share a similar neurochemical and gene expression pattern and neurons that express somatostatin make up a well defined population on both.The somatostatinergic neurons of the EAc (SSTEAc) coexpress GABA, exerting a mainly inhibitory transmission and recent literature brings forward evidence of its involvement on the regulation of feeding behaviour and energy homeostasis. Furthermore, previous and unpublished work from our group have evaluated the relevance of GABAergic signalling from somatostatin neurons over aspects of energy metabolism. The data gathered suggest that lack of this signalling results on a phenotype of malnutrition and overall metabolic dysregulation and further analysis have shown that PBN neurons are hyperactivated after loss of GABAergic signalling from SST neurons.Based on this, the present project aims to evaluate the role of EAc somatostatin neurons over different neural circuits that satiety, particularly PBN neurons, as well as other aspects of feeding behaviour. For that, it is proposed a set of experiments combining genetically modified mouse models and viral injections to manipulate these neural circuit. (AU)