Project Details
Projekt
Dopamine function in working memory networks and its dysfunction in a mouse model of schizophrenia
Applicants
Dr. Sevil Duvarci; Professor Dr. Jochen Roeper; Professorin Dr. Gaby Schneider; Dr. Torfi Sigurdsson
Subject Area
Cognitive, Systems and Behavioural Neurobiology
Term
from 2016 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 322169167
Schizophrenia is a chronic and devastating psychiatric disease characterized by a dysfunction of the dopamine (DA) midbrain system and severe cognitive dysfunctions including an impairment of working memory (WM). Our aim is to understand how the DA system interacts with the prefrontal cortex (PFC) to guide WM behavior in mice and how these interactions are affected in a mouse model of schizophrenia. Specifically, we will focus on a 4 Hz oscillation that we identified in the previous funding period that synchronizes neuronal activity in the ventral tegmental area (VTA) and the PFC in a WM-dependent manner and which is disrupted in a schizophrenia mouse model. We will use previously developed viral tools to optogenetically identify PFC and VTA projection neurons connecting the two structures. We will then use novel statistical tools to characterize their respective WM-related firing patterns at the level of individual neurons and neuronal populations. Finally, optogenetic manipulations of projection-specific neuronal subpopulations within the VTA and PFC will enable us to test their causal role in VTA-PFC synchrony and WM behavior. Based on these insights, we will attempt to rescue deficits in VTA-PFC network activity and WM behavior in our schizophrenia mouse model using cell-specific optogenetic activation. Taken together, our results will yield important mechanistic insights into VTA-PFC interactions, their role in normal cognitive functioning and their breakdown in psychiatric disease models.
DFG Programme
Priority Programmes
