Electrophysiological study of serotonergic modulation of the prefrontal cortex during postnatal development

• Grant number: 22/00850-3
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2022 - October 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Roberto De Pasquale
• Grantee: Roberto De Pasquale
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Fernando da Silva Borges ; Guilherme Shigueto Vilar Higa

Abstract

The prefrontal cortex (PFC) is a region involved in planning cognitive behaviors, emotional responses, and decision making. An important part of the development of this cortical area occurs during the early postnatal period. In rodents, this phase corresponds to the first three weeks of life. During this period, PFC neurons show high excitability and develop endogenous waves of excitatory activity. These properties are believed to play a decisive role in the formation of new synaptic connections and in the definition of primordial circuits, with consequences that also impact adulthood. Serotonin (5-HT) stands out among the factors that could play an important role in this process. Its receptors act directly on excitability, altering ionic conductance and also affect synaptic potentiation (LTP) mechanisms that are necessary for the formation of new synapses. In particular, there is evidence suggesting that 5-HT7 and 5-HT3 receptors could play an important role in defining the window of heightened excitability and synaptic strength in postnatal development. It is known that the 5-HT7 receptor increases excitability and favors LTP in other brain regions. Its early expression in the PFC suggests that it could favor the high arousal levels of the first three weeks of the postnatal period, possibly through modulation of the TREK-1 potassium channel. In turn, the 5-HT3 receptor acts on the PFC, strengthening GABAergic synapses and its action tends to be more impactful after the third week of life, thus being the factor responsible for closing the period of high excitation. This project aims to use intracellular electrophysiological recording techniques and evaluation of protein expression and activation via Western Blot to study the effects of 5-HT on neuronal excitability, LTP and GABAergic inhibition in PFC neurons during postnatal development, focusing on the role of serotonin and 5-HT7 and 5-HT3 receptors as determinants of the temporal window of high excitability and synaptic potentiation. (AU)