NeuroNetwork 13

Project titel: Dopaminergic modulation of working memory-related persistent neuronal activity in auditory cortex: from molecules to behavior Project leader: Janelle Pakan, Ying Huang, Motoharu Yoshida

Throughout our lives, we obtain and recall a potentially infinite amount of information. However, at any given moment, only a limited amount of information can be forefront in our minds. This 'online' information allows us to detect changes in our environment, communicate with others, reason and problem solve, and to complete many tasks in our everyday lives. This cognitive function to store information online and over short periods of time is termed working memory and is a fundamental prerequisite for us to perform everyday functions. Working memory deficits are evident in many patients with neurodevelopmental and neurodegenerative diseases, and have been postulated to be related to alterations of specific signaling systems used by the brain. One important neuromodulatory signaling system in this regard is the dopaminergic system; changes in the levels of dopamine in the brain have been directly linked to cognitive and working memory performance in both health and disease. However, the underlying neuronal mechanisms through which dopamine affects working memory processes remain largely unknown, making it difficult to develop effective treatments. In this project, we will investigate the role of dopamine on working memory from the molecular level in mice to the cellular and behavioral levels in monkeys with a focus on persistent neuronal activity: a cellular correlate of working memory. Our goal is to establish a coherent understanding of the cellular to network-level neural activity supported by specific dopaminergic receptors across species and to directly correlate the modulation of dopaminergic activity to the performance on working memory tasks. The complementary and translational nature of our project will foster the development of advanced drugs and strategies to treat disorders involving working memory deficits and alternations of dopaminergic signaling, such as in schizophrenia and Parkinson’s diseases.