Serotonergic modulation of medial prefrontal cortex and early life stress

• Grant number: 24/21584-5
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: June 16, 2025
• End date: September 15, 2025
• Field of knowledge: Biological Sciences - Biophysics - Biophysics of Processes and Systems
• Principal Investigator: Roberto De Pasquale
• Grantee: Emily Cruvinel dos Santos
• Supervisor: Minae Niwa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Alabama at Birmingham (UAB), United States
• Associated to the scholarship: 23/14230-0 - Serotonergic modulation of prefrontal cortex neuronal excitation in postnatal development, BP.IC

Abstract

The prefrontal cortex (PFC) is an essential brain region involved in cognitive functions and emotional regulation. Like other cortical areas, a significant portion of its development occurs during the early postnatal period, and any disruptions to this developmental process may contribute to the onset of psychiatric disorders. Previous studies have provided evidence that the PFC exhibits a neuronal excitation-inhibition balance (E/I balance) that is skewed towards elevated levels of excitation during early life. This heightened E/I balance is crucial for the formation of synaptic connections and the overall maturation of the PFC. Among the various neuromodulators that influence neuronal excitation during this critical period, serotonin (5-HT) plays a particularly significant role. It is known to enhance the excitability and glutamatergic transmission within the PFC by activating 5HT2A receptors. Nevertheless, the current body of research remains unclear regarding the specific actions of 5-HT, as its effects can vary considerably across different subpopulations of PFC neurons. This project intends to investigate the serotonergic modulation of E/I balance within a specific subpopulation of neurons located in the prelimbic area of the PFC (PL), which receive projections from the medial cingulate gyrus (mCg). Recent experimental findings indicate that exposure to early life stress (ELS) results in the hypofunctionality of this projection, which may hinder the proper maturation of the PFC and lead to sociability deficits in adulthood. Using an animal model subjected to ELS, our project will explore the serotonergic modulation of E/I balance through the labeling techniques combined with intracellular recordings.