Ethanol effects on the direct striatal pre-synaptic inputs on to the Globus Pallidus and the Substantia Nigra pars reticulata.

• Grant number: 23/09467-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 04, 2024
• End date: March 03, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Karina Possa Abrahão
• Grantee: Sara Emi Matos Mendes Ferreira
• Supervisor: David Lovinger
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Laboratory for Integrative Neuroscience (LIN), United States
• Associated to the scholarship: 20/12260-0 - The effects of alcohol on the direct pathway of dorsal striatum sub-regions: a central component in decision-making, BP.DR

Abstract

Alcohol consumption is a serious public health problem. This drug modifies the function of brain regions crucial for decision-making, such as the Basal Ganglia. The dorsal striatum, a central nucleus of the Basal Ganglia, contains GABAergic efferent neurons classified as the indirect and the direct pathways. Although much attention has been given to the striatal direct pathway projections to the Substantia Nigra pars reticulata (SNr), these neurons also send bridge collateral projections to the external part Globus Pallidus (GPe). In this project, we aim to compare the effects of ethanol on the striatal projections to the SNr and to the GPe. We will use in vitro and in vivo photometry to evaluate how ethanol intoxication modifies pre-synaptic functions, using a fluorescent calcium indicator (GCamP). AAV-DIO-GCamP virus will be stereotaxically injected into the dorsal striatum of the EY262-Cre mice (cre recombinase expression is driven by the D1 receptor gene). For the in vitro photometry tests, brain slices from naïve and chronically ethanol-treated mice (12x i.p. administration of 2.0 g/kg ethanol), containing the SNr and/or the GPe, will be prepared and recorded with a photometry setup and ethanol will be bath applied to analyze if previous exposure to ethanol can change in vitro acute ethanol effects. In addition, another group of mice will be implanted with fiber optics onto the SNr and/or the GPe for in vivo recordings of the pre-synaptic activity before and after acute and chronic 2.0 g/kg ethanol or saline administration. We expect to have a better comprehension of how ethanol can change the physiology of this neuronal pathway which contributes to decision-making behaviors.