Priya Rajasethupathy, MD, PhD

Prize Winner

Position

Jonathan M. Nelson Family Associate Professor and Head of Lab Neurosciences and Behavior

Prize

MIND Prize

Cohort

2023

Program

MIND Prize

Institution

The Rockefeller University

Website

www.rajasethupathylab.com

Project

Leveraging Neuron-Glia Crosstalk in Thalamo-Cortical Circuits for Cognitive Rescue

Vision

How are brief interactions in our external world codified into lasting internal representations in our brain? We develop molecular, cellular, and brain imaging approaches to capture the evolving nature of memories across the brain over time. Our vision is to be able to understand how a memory progresses from inception, to reorganization, to long-term stabilization.

About

Priya Rajasethupathy is currently the Jonathan M. Nelson Family Associate Professor and Head of Lab at the Rockefeller University. She obtained her BA from Cornell University, and an MD/PhD in Neuroscience from Columbia University, working with Eric Kandel. She did her post-doctoral work at Stanford University with Karl Deisseroth. Priya is a Vallee, Searle, and Klingenstein Scholar and has been a recipient of an NIH New Innovator Award, Presidential Early Career Award, and the MIND Prize.

Innovation is approaching the problem in a new way that allows the puzzle pieces to come together into a new understanding or framework.

Basic genetic or neural circuit mechanisms driving cognitive variability are poorly understood. Why do some individuals have difficulty with attention, short-term memory, and executive functions, while others are particularly adept? In recent work from the lab, we studied a population of genetically diverse mice and identified a small genetic locus on chromosome 5 that contributes to substantial variability in short-term memory. Within this locus, we identified a causative gene, a brain-specific orphan GPCR, which functions in thalamus neurons to promote short-term memory. Since then, we have discovered additional genetic loci linked to short-term memory but that harbor primarily non-neuronal genes, including those functioning predominantly in astrocytes and oligodendrocytes. It is thus possible that glial-neuron crosstalk in the thalamus-cortex circuit promotes signal propagation and metabolic support to sustain short-term memory, and can be targeted for cognitive rescue in neurodegeneration. Indeed, short-term memory deficits are prodromal and prognosis-driving in neurodegenerative disease, where subtle momentary lapses manifest as subsequent deficits in planning, decision-making, memory and higher order executive functions.

"I am honored to receive the MIND prize and to be a part of a supportive and inspiring network of colleagues. The MIND prize will allow us to explore the brain pathways that are used for memory maintenance and recall, and to identify cells types in these circuits that are most vulnerable during neurodegeneration, which may serve as targets for resilience and recovery."

Emerging studies have identified re-programming of glial cell-types in patients with dementia, and broad perturbations to astrocytes have led to cognitive improvements in mouse models. Thus, in this proposal we explore the possibility that cooperation between neurons and glia in the thalamus-PFC circuit is critical for short-term memory and can provide functional targets for cognitive rescue in neurodegenerative disease.