Description of Research Expertise

We, at the Mukherjee lab, take a systems neuroscience approach to understand how brain circuits support complex cognition and how their dysfunction contribute to psychiatric disorders. Our research primarily focuses on the prefrontal cortex (PFC) and its dynamic interactions with key brain regions like the hippocampus and thalamus.

We use an integrative approach, combining behavioral physiology with modern techniques such as virus based circuit tracing, single-cell transcriptomics, and opto/chemo-genetic perturbations. Using rodents and treeshrews as model organisms, we investigate how specific populations of neurons within the PFC and across its wider network work together to support cognitive functions like memory consolidation and inference based reasoning. By studying these circuits in freely behaving animals we formulate hypotheses about their functional roles and causally validate them using optical and pharmacological tools.

A key goal of our work is to understand the functional maturation of cognitive control circuits across normal development and their fidelity in animal models of psychiatric disorders. Ultimately, we hope to identify cell type specific circuits for targeted neuromodulation aimed at enhancing cognitive function in psychiatric and neurological disorders.​

We are based out of the Center for Brain Research in Development, Genetics and Engineering (BRIDGE) at the Children's Hospital of Philadelphia and the University of Pennsylvania. These two world renowned institutions offer state of the art infrastructure, strong peer networks and deep domain expertise in all areas of neuroscience.



Research Interests:

1. Molecular Signatures and Connectivity Maps of Cognitive Control Circuits

How does the activity patterns generated by the prefrontal cortex transform into cognitive control signals? This is a central challenge in systems neuroscience and one of the main focus areas of our lab. 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 we combine 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.


2. Principles Governing the Maturation of Cognitive Control Across Adolescence

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. We, at the Mukherjee lab, investigate the emergent properties of the adolescent PFC that drive increased exploration and risk taking. We specifically focus on:

- Thalamocortical circuits that support decision making in noisy
environments.

- Dopaminergic modulation of prefrontal circuit function in adolescence.


3. Cell-type specific sensitive periods of vulnerability of the PFC

Protracted maturation of the 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. Our research 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.