The effects of alcohol on the direct pathway of dorsal striatum sub-regions: a central component in decision-making

• Grant number: 20/12260-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2021
• End date: November 29, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Karina Possa Abrahão
• Grantee: Sara Emi Matos Mendes Ferreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/01686-0 - I cannot stop after the first ‘drink’! Alcohol effects on the inhibitory control brain systems, AP.JP
• Associated scholarship(s): 23/09467-0 - Ethanol effects on the direct striatal pre-synaptic inputs on to the Globus Pallidus and the Substantia Nigra pars reticulata., BE.EP.DR

Abstract

Alcohol (or ethanol) consumption is a serious public health problem. This drug modifies the function of brain regions related to decision-making, such as the basal ganglia. The dorsal striatum, a central nucleus of the basal ganglia, is subdivided into medial, lateral and caudal subregions. Few studies have evaluated the effects of ethanol on these dorsal striatum subregions. The striatum contains GABAergic efferent neurons classified as the direct and the indirect pathways neurons. Although most studies have focused on striatal direct pathway projections to the Substantia Nigra pars reticulata (SNr), these neurons also send collateral projections to the target region of the indirect pathway, the Globus Pallidus (GP). There are no data comparing the effects of ethanol on the direct and collateral projections to the SNr and to the GP. In this project, we will evaluate ethanol's impact on the striatum subregions and the direct pathways to SNr and GP associated with decision-making. C57BL/6J and transgenic mice will receive acute or chronic ethanol treatment in order to evaluate the activation of the direct pathway neurons in the striatum subregions. For this, we will use the immunofluorescence staining of Fos expression. We will also use slice photometry to evaluate the ethanol effects on the synaptic projections of direct pathway neurons to SNr and to GP, using a virally expressed calcium indicator: GCamP6f. Finally, we will study the behavioral consequences of ethanol's in vitro effects by artificially mimicking them with chemoreceptors (DREADDs). (AU)