Mukherjee Laboratory Research Overview

How do the activity patterns generated by the prefrontal cortex (PFC) transform into cognitive control signals? This is a central challenge in systems neuroscience and one of the main focus areas of the lab's research. Uncovering the principles of such transformations could provide key insights into the computational algorithms and neurobiological substrate of cognition and its dysfunction in psychiatric disorders.

To this end, the team combines activity based tagging of neural ensembles, single cell transcriptomics, in vivo electrophysiology, and well-parameterized behavior tasks to probe the cell type-specific microcircuits within the PFC and thalamus and the hippocampus that underlie cognitive control over:

• Perceptual and motivational decision making
• Long term memory consolidation towards rule learning.

Adolescence is a critical period in development marked by heightened exploration and risk-taking behaviors. Such behaviors are theorized to be evolutionary adaptations essential for refining cognitive control over survival and reproductive success. The Mukherjee Lab investigates the emergent properties of the adolescent prefrontal cortex that drive increased exploration and risk taking. The lab's work focuses on:

• Thalamocortical circuits that support decision making in noisy environments
• Dopaminergic modulation of prefrontal circuit function in adolescence.

Protracted maturation of the prefrontal cortex (PFC) across adolescence renders it vulnerable to disruptions from stressors encountered at this age, such as substances of abuse. Notably, many psychiatric disorders, like schizophrenia, that are marked by cognitive deficits first emerge during this period. Research in the Mukherjee Lab focuses on:

• Identifying temporal windows when cell type-specific PFC circuits deviate from typical development in models of neurodevelopmental and psychiatric disorders
• Developing circuit-specific interventions during adolescence that promote long-term cognitive enhancement.