The role of ventral subículum > juxtadorsomedial region of the lateral hypothalamus pathway in the passive avoidance response to aversive sites

• Grant number: 21/01642-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2022
• Effective date (End): February 28, 2025
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Newton Sabino Canteras
• Grantee: Karolina Domingues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diferent types of aversive stimuli are processed by parallel circuits that promote the expression of appropriate behaviors for each situation. However, although well defined, there can also be an overlap. For example, very different stimuli such as restraint stress and social defeat, exposure to snake and passive avoidance mobilize common areas, such as areas of the septo-hippocampal pathway and perifornicial areas of the lateral hypothalamic area, particularly the juxtadorsomedial region (LHAjd). This regions is of special interest for it recieves information from the ventral subículum (SUBv), which is involved in contextual processing, and conects to the premamilary nucleus and periaquedutal grey matter, which are regions involved in the expression of avoidance behaviors. Therefore, it was postulated that the LHAjd could be involved in the detection of potential dangerous places for the animal, such as the environmental boundaries imposed by the presence of a predator or an aggressive co-specific, and control the risk assessment behaviors during passive avoidance. Initially we will determine the anatomical organization of the SUBv > LHAjd pathway. To test the hypothesis that the SUBv > LHAjd pathway is involved in avoidance of aversive places we will pharmacologically inhibit the SUBv, as well as optogenetically inhibit the projection SUBv > LHAjd and test the passive avoidance in a context paired with electrical shock. Using the DD-Cre strain we will induce the expression of archaerhodopsin in the cells of the LHAjd during passive avoidance and test how the optogenetic inhibition affects this behavior. We also propose unitary recordings of the LHAjd cells to correlate with the behavioral responses during passive avoidance. Next we will use the imunofluorescence technique for Fos protein combined with in situ hybridization for the c-FOS mRNA (IF-FISH) to determine de degree of superposition of the LHAjd cells that are active in both passive avoidance and social defeat. And finally, in case there is such a superposition, using the DD-Cre strain we will induce the expression of archaerodhopsin in the LHAjd cells mobilized during social defeat and test how their optogenetic inhibition affects the passive avoidance behavior.