Involvement of medial prefrontal cortex neuronal ensembles and its perineuronal NETs on incubation of cocaine craving

• Grant number: 20/01343-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2020
• End date: October 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Giovanna Victória Lopes Costa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories, AP.JP2

Abstract

Correlational data suggests that learned associations are encoded within sparsely distributed patterns of neurons called neuronal ensembles that are selectively activated during learned behaviors. Until recently it has been difficult to prove that neuronal ensembles mediate learned behaviors because both traditional pharmacological and lesion methods, and newer optogenetic and chemo genetic methods alter the activity of neurons regardless of whether they were selectively activated or not activated during learned behaviors. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviorally activated and non-activated neurons. Based on these considerations, we propose to combine some methodologies, considered as state-of-art (overlap, optogenetic regulation, FACS, causal role experiments, c-Fos::teop-Cre and LacZ rats) to assess different aspects of ensemble-specific neuroadaptations in different brain areas in context-induced reinstatement of alcohol-seeking and incubation of cocaine seeking. Understanding the role of these neuronal ensembles in behavior and the ways that repeated drug administration alters them will help us to understand how drugs of abuse produce the learned behaviors associated with addiction. (AU)