How much of our behavior and its disorders are determined by our genes and by our environment? This nature-nurture debate has continued for centuries by both philosophers and scientists. We now know our behavior reflects neural circuits sculpted by experience during “critical periods” in postnatal life. Such heightened plasticity declines into adulthood, often limiting recovery of function. On the other hand, the adult brain needs stability. Failed stabilization can disrupt circuit computations by allowing modification by undesirable information, which may lead to mental disorders. How does the brain solve this stability-plasticity dilemma? The goal of our lab is to identify the mechanisms of developmental critical periods to establish (1) Perception and (2) Cognitive & (3) Social Behavior relevant to neuro-developmental and psychiatric disorders. Our strategy is to use visual system, a premier model of critical period for cortical plasticity, to discover molecular/ circuit mechanisms, and then apply these mechanisms as unique tools to dissect more complicated critical periods for cognitive behaviors such as attention and social cognition. We are an active member of Center for Neurotechnology and Behavior and Center for Affective Neuroscience at Mount Sinai.

Another current line of research aims to examine the mechanisms prefrontal social circuit maturation. Social behavior is commonly dysregulated in neurodevelopmental disorders, yet little is known about the mechanisms governing social behavior development. Studies in humans and animals demonstrate that the prefrontal cortex is important in regulating social cognition (see our recent review Front Psychology 2015). The goal of this line of research is to identify molecular and circuit mechanisms in prefrontal cortex regulating juvenile critical period for experience-dependent development of social behavior. By combining intersectional approaches of behavior, cell-type-specific manipulation of neural activity and gene expression, our recent studies identified the role of specific excitatory and inhibitory cell-types in social behavior development (Nature Neuroscience 2020, Nature Communications 2020). Identification of a critical period and underlying mechanisms for social circuits and behavior would eventually improve diagnosis, prevention and treatment of psychiatric disorders. Currently supported by NIMH R01, One Mind, and Simons Foundation.

Experience-dependent cortical plasticity is heightened during developmental critical periods but declines into adulthood, posing a major challenge to recovery of function following injury or disease later in life. Our research aims to identify the mechanisms of experience-dependent cortical plasticity. Using visual system, a premier model of critical period, we take an integrated approach, combining molecular, anatomical, imaging, electrophysiological methodologies (e.g. in vivo viral gene transfer, optogenetics, chemogenetics, and two-photon time lapse imaging) (Science 2010, J Neurosci 2015, J Neurosci 2016, eNeuro 2017, Scientific Reports 2018, J Neurosci 2020). Our study would have direct implications for Amblyopia, a condition with limited adult-applicable treatment affecting 2–5% of the human population, but also for brain injury repair, sensory recovery, and the treatment of neurodevelopmental disorders. Currently supported by National Eye Institute R01.

Mechanisms driving critical period circuit development are well described in sensory cortex—but poorly characterized for prefrontal cortex dependent cognitive behaviors. A second major goal of our research is to examine the molecular and circuit mechanisms to prefrontal cortex maturation to establish proper cognitive behavior. We combine in vivo circuit-specific manipulation/monitoring of neural activity and gene expression in behaving mice using a translationally-relevant touchscreen behavioral testing. We recently found that frontal top-down cortico-cortical neurons projecting to visual cortex, which are preferentially recruited after errors to adjust attentional behavior (Neuron 2021), undergo activity-dependent integration of local inputs during adolescence sensitive period (Nature Communications 2020), followed by nicotinic signaling-dependent shift in local and long-range input balance to establish proper attentional behavior in adulthood (Science Advances 2021). Identified circuit-associated mechanisms would promote translation of our basic research findings to clinical research to improve diagnosis, prevention and treatment of neuro-developmental disorders. Currently supported by NIMH R01.