Navneet Vasistha

Rescuing early parvalbumin interneuron dysfunction in schizophrenia

Parvalbumin-expressing interneurons (PVIs) are a crucial cellular population in the brain which regulate neuronal circuits. As suggested by their name, they are characterized by the expression of parvalbumin, an activity dependent calcium-binding protein. Further, genetic or environmental disturbance of PVIs in mice leads to behavioural changes reminiscent of schizophrenia.

Our preliminary studies in juvenile mice shows an increased expression of parvalbumin in models of schizophrenia. This indicates heightened activity of PVIs that can affect the precise development of neuronal circuits. To follow this up, I will use more sensitive methods to study PVI activity in wild-type and mice models of schizophrenia. In parallel, I will also use state-of-art single-cell RNA sequencing to identify molecules that are dysregulated in PVIs. This will provide us with candidates that can be targeted via genetic or pharmacological interventions to rescue PVI activity.

This approach will shed new light on the maturation of inhibitory neurons in the brain and also provide fresh ideas for therapeutic approaches in schizophrenia.

Mentors

Basic Mentor: Associate Professor Konstantin Khodosevich, Biotech Research & Innovation Centre (BRIC), University of Copenhagen

Clinical Mentor: Professor Jens Damsgaard Mikkelsen, Neurobiology Research Unit, Rigshospitalet