Mapping Thalamo-striatal Neuronal Circuits Underlying Motivational Drive

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Project Summary Motivated goal-directed behaviors act as mechanisms that ensure and promote survival in animals. However, the mechanisms that underlie motivated behaviors are not fully understood. This is important because deficits in motivation have been linked to various psychiatric disorders. Current research on this topic have largely focused on investigating the contribution of the dopaminergic meso-accumbens pathway to this process. However, the role that glutamatergic inputs to the NAc play in the control of motivation is far less clear. My previous research has shown that the paraventricular nucleus of the thalamus (PVT) sends prominent glutamatergic projections to the accumbens and in turn receives homeostatic signals from areas such as the hypothalamus and brainstem. As such, the PVT has been proposed as a brain area that integrates visceroceptive signals and to promote adaptive responses via projections to the NAc. Moreover, previous research and my preliminary data show that the PVT has two major distinct subpopulations of neurons, Type1PVT and Type2PVT, which differ on their genetic identity, connectional features, and functionality. However, the precise mechanisms by which these PVT projections to the NAc influences different components of motivated behavior remains unknown. To address this gap, we are examining the functional organization of the PVT-NAc neuronal circuit by using a multidisciplinary approach that includes mouse genetics, electrophysiology, neuroimaging and behavior. These findings will advance our understanding of the contributions of thalamo-striatal circuits promoting motivational drive that can create fundamental insights to develop novel approaches for individuals suffering from motivational deficits Relevance: Motivational deficits are a core feature of highly prevalent psychiatric disorders (e.g., drug- abuse or obsessive-compulsive disorder, major depressive disorder, and others), this research may provide insights into potential therapeutic targets for these psychiatric disorders. Lastly the research conducted here seeks to provide fundamental insight into the neural mechanisms that mediate motivated behaviors.