Amar Sahay, Ph.D.

Massachusetts General Hospital

Harvard Medical School

Broad Institute of MIT and Harvard

asahay@mgh.harvard.edu

Sahay Lab

PubMed Site

Amar Sahay Publications

Re-engineering neural circuits to restore cognition in brain disorders

Adaptively responding to the environment is critical to optimal navigation of our world. The hippocampus plays a critical role in this process by generating memories of our experiences, transferring these memories for storage or consolidation to the prefrontal cortex and recalling and routing memories to subcortical circuits to calibrate defensive and motivated behaviors (e.g., approach, cadence, avoidance, reward seeking). It is intuitive to think how aberrations in hippocampal circuit mechanisms underlying memory processing or storage or linkage of mnemonic information with subcortical circuits are the basis for cognitive impairments in neurodevelopmental disorders, aging and Alzheimer’s Disease. The mission of the Sahay lab is to generate insights to reverse these aberrations through investigation of molecular, circuit and network plasticity mechanisms supporting cognition.

Our projects are governed by the intuitive logic that elemental features of wiring diagrams are prescribed by proteins, whose functions have been fine-tuned by evolution and experience. By identifying genetic and molecular determinants of elemental features of circuit wiring diagrams, we strive to ascribe causal relationships between circuit motifs and function. Towards this goal, we have undertaken a multifaceted bottom-up approach that integrates inducible mouse- and viral-genetics, pharmaco- and optogenetics, synaptic tracing, in vivo awake behaving optical imaging, ex vivo electrophysiology, in vivo electrophysiological recordings and behavioral analysis. Ongoing efforts have resulted in discoveries that enable us to:

A. Re-engineer connectivity of inhibitory microcircuits and reverse impairments in GABAergic inhibition and cognition in NDD risk models, aging and AD.

B. Restore lipid signaling to reverse cognitive impairments in aging and AD.

C. Rejuvenate hippocampal circuitry with new neurons to restore GABAergic inhibition and preserve cognition in aging.

D. Harness a novel brain circuit to regulate feeding.

Biosketch

Dr. Sahay is Professor of Psychiatry and James and Audrey Foster MGH Research Scholar at the Center for Regenerative Medicine at MGH and Harvard Medical School. He is an Associate Member of the Broad Institute of MIT and Harvard.