We aim to understand how early life experiences, such as sensory inputs, social bonding, stress and substance exposure, impact brain circuit assembly and mature function in models of psychiatric illness.
Research
We apply a multi-dimensional approach to elucidate the effects and consequences of early life experiences from neonates to adults, assessing transcriptional, circuit, neuronal activity, and behavioral changes on the entire developmental time axis. Understanding the developmental trajectories following early life experiences holds the key to developing diagnostics and early intervention for many psychiatric illnesses. Currently lab focuses the following three specific areas:
The Role of Oxytocin on the Development of Social Behavior
Touch contributes powerfully to parent-infant interactions that are fundamental for early social behavior development. Abnormalities in tactile perception are prevalent features in individuals with autism spectrum disorders (ASD), exacerbating the core social deficits. While the neural mechanisms underlying the interplay between tactile input and social behavior is not yet known, a prominent route through which social information can be conveyed to neurons is oxytocin signaling. In neurons, oxytocin modulates inhibition to increase signal-to-noise ratios, promote long-term synaptic plasticity, and enhance the salience of socially-relevant stimuli. We are investigating how oxytocin facilitates the development of social touch on a circuit level. We use a combination of techniques including mouse genetics, slice electrophysiology, longitudinal in vivo 2-photon imaging on behaving animals to reveal how circuits underlying whisker-dependent social interaction is established.
Circuit Dysfunction in PTSD
PTSD is a debilitating disorder involving intrusive memories of a traumatic events, which are due in part to an inability to modify responses to stimuli that are no longer threatening – a process known as extinction. The medial prefrontal cortex (mPFC) plays a critical role in extinction, however the circuit-level mechanisms that support extinction learning in the mPFC are not completely understood. Recent TWAS and gene expression studies on PTSD postmortem brain revealed numerous dysregulated genes expressed in GABAergic neurons in the dlPFC that are also key drivers capable of coordinating transcriptomic organization. We aim to understand how these genes are involved in fear extinction on cellular, circuit and functional levels with an emphasis on the developmental period, leveraging new technologies for cell type-specific genetic manipulations and 2-photon imaging through chronically implanted microprisms. *Image from Girgenti et al. Nat. Neurosci. 2021
Early-Life Cannabinoid Exposure on Circuit and Behavior Maturation
Cannabis consumption during pregnancy and lactation has reached 7-15% in recent year, and will likely continue to rise due to widespread legalization. Increased availability of cannabis has led to the public perception that it is a safe natural remedy for pregnancy-related ailments and postpartum mood disorders. However, growing clinical and preclinical data suggest prenatal and perinatal cannabis exposure is associated with long-term neurodevelopmental consequences in children, including sensorimotor, emotional, and cognitive deficits, as well as increased risk for illicit drug use in adolescence and adulthood. The neural mechanisms and sensitive periods underlying these long-term effects are still poorly understood, making it challenging to provide accurate medical advice for risk assessment of cannabis use in mothers. To address this challenge, our overall goal is to identify the developmental processes and circuit-specific mechanisms underlying the effects of early-life cannabinoid exposure on cognitive behaviors. We will leverage our novel longitudinal 2-photon imaging technique in developing mice to assess the impact of cannabinoid exposure.
Effect of Early Life Stress in Development and Adulthood
Early life stress exerts profound short- and long-term effects on the susceptibility to mood disorders, such as depression and anxiety, in adolescents and adults. Although signs of psychiatric disturbance are typically not expressed until later life, signs of dysfunctional social behavior have been found as early as infancy. To date, most animal studies of early stress focused on its impact on adult brain and behavior, while knowledge on the precise developmental trajectories following stressful events remains limited. We are interested in assessing molecular and functional changes taking place after stress during development. We will apply transcriptomic analyses and our functional approaches to understand how developmental changes correspond to alterations in network activity and social behaviors later in life.