Grant: Fellowship - Priority Announcement: Aging

While Parkinson's disease (PD) is classically characterized by motor symptoms, patients also exhibit marked deficits in social cognition. Notably, patients experience declines in cognitive empathy- the ability to infer the emotional states of others. Impaired empathy may be tied to pathology in higher processing centres of the brain. The accumulation of abnormal proteins, in what are known as Lewy bodies, is a hallmark of PD and is observed most prominently in the hippocampus (HPC). While the HPC is known to be critical for memory, its importance in social and emotional functions has emerged in recent years. I hypothesize that in PD, the presence of Lewy bodies disturbs activity patterns in the HPC which normally support the processing of social and emotional cues leading to impaired social memory and empathy. My objective is to elucidate the activity patterns in the HPC supporting empathy and to uncover alterations to this activity in a mouse model of PD. I will first implement a model of selective HPC Lewy body pathology using a combination of viral and genetic approaches in mice. These mice will be tested for their ability to recognize the identity (social memory) and the fearful states of conspecific individuals (empathy). Throughout the performance of these behavioural tests, the activity of large numbers of cells in the HPC will be simultaneously monitored, and disruptions to their coordinated activities will be investigated. These experiments will causally connect molecular pathology in cells to altered task-related neural representations to the manifestation of behavioural impairments. The proposal's multi-level approach allows for a comprehensive mechanistic understanding of the impact of Parkinson's pathology on behaviour. The project's findings may pave the way to targeted interventions for social cognition deficits in Parkinson's disease and in neuropsychiatric illnesses broadly.