1. Molecular Signatures and Connectivity Maps of Cognitive Control Circuits
How does the activity patterns generated by the PFC 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 across the PFC, thalamus and the hippocampus that underlie cognitive control over:
1. Perceptual and Motivational decision making, and
2. Long term memory consolidation towards rule learning.
3. Cell-type specific sensitive periods of vulnerability of the PFC
The Prefrontal cortex has a protracted period of maturation that renders it vulnerable to stressors encountered at this age, such as substances of abuse. Many psychiatric disorders, like schizophrenia, that are marked by cognitive deficits first emerge during this period. Our research specifically focuses on the transitory period between adolescence and adulthood to:
1. Identify temporal windows when cell type–specific PFC circuits deviate from typical development in models of neurodevelopmental and psychiatric disorders.
2. Develop circuit-specific interventions during adolescence that promote long-term cognitive enhancement.
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. These 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:
1. Thalamocortical circuits that support decision making in noisy environments.
2. Dopaminergic modulation of prefrontal circuit function in adolescence.