Participation of the Nucleus Incertus in the behavioral activation process

• Grant number: 25/08983-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: June 30, 2029
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Newton Sabino Canteras
• Grantee: Renata Silva Jorge
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/14359-0 - Anatomic, functional and molecular studies of neural systems involved in behavioral activation, fear memory and inhibition of defense responses, AP.TEM

Abstract

A fundamental issue in psychiatric disorders such as anxiety and depression is the alterationof behavioral activation levels. The concept of behavioral activation is still underexplored and refers to processes of behavioral regulation related to the overall level of activity, degree of alertness, and attentional engagement. This project will investigate a site in the pontine periventricular region known as the nucleus incertus (NI), which plays a critical role in behavioral activation. Initially, we willexamine various behavioral situations in which we aim to contrast high and low behavioral activation. In these different behavioral contexts, we will assess the activation pattern of the NI. We will use a neuromedin B (NMB) Cre transgenic mouse for NI manipulation, as NI cells differentially express NMB compared to neighboring structures. First, we will validate this transgenic model by evaluating the efferent and afferent projection patterns of NMB-positive cells in the NI. Once the hodological pattern of NMB-positive NI cells is validated, we will determine, through optogenetic experiments, how the activation and inhibition of the NI can influence behavioral states of low and high activation,respectively. Thus, the results of this investigation will provide important insights into the role of the NI in controlling behavioral activation. Subsequently, we will determine the activation patterns of the main afferent sources of the NI under conditions of high and low behavioral activation and investigatehow the manipulation of projections from these afferent sites to the NI can modulate activation and inhibition in the examined behavioral models. Together, the results of this project may provide critical information for a better understanding of behavioral activation and its regulation, as well as its possible implications for psychiatric disorders such as anxiety and depression. (AU)