RESEARCH

Behavioral time scale plasticity (BTSP) is important for the induction of CA1 place cells. In this non-Hebbian plasticity mechanism, presynaptic inputs get paired with the large postsynaptic depolarization over seconds to potentiate synapses. Given the unique nature of this plasticity protocol, we hypothesize distinct roles of kinases underlying this plasticity. Previously, we found that novel dendritic CaMKII activity underlies BTSP (Jain et al., 2024, Nature). Using behavior, two-photon fluorescent lifetime imaging and synaptic electrophysiology, we are now exploring the molecular mechanisms that confer synapse specificity to BTSP. Moreover, we plan to investigate the behaviorally relevant homeostatic mechanisms activated following BTSP induction or place cell formation. 

This project investigates mechanisms responsible for the altered synaptic and brain function observed in autism spectrum disorders (ASD). By reprogramming skin or blood cells from ASD patients into iPSCs, we can generate patient-specific neurons that will provide a model to study how autism impacts neuronal development and synaptic function. Advanced imaging, electrophysiology, and molecular biology techniques will be used to assess the morphology, connectivity, and functional activity of these neurons. Synaptic density, strength, and neurotransmitter release will be among the key matrices. The use of patient-derived neurons offers an accurate and human-relevant model to understand the pathophysiology of autism, with the potential for developing new biomarkers and treatments. Ultimately, this work could pave the way for personalized therapies aimed at correcting the neuronal and synaptic deficits contributing to ASD. 

Spino-cerebellar ataxia type 12 is a rare form of Ataxia but is prevalent in the Indian population, especially among the Agrawal community. At CHINTA, stem cell biologists have successfully developed induced pluripotent stem cell-derived 2D and 3D neuronal cultures from these patient population and their control counterparts. As a part of this collaboration, we are investigating how the different electrophysiological or synaptic properties are affected in these neurons. 

The anterior cingulate cortex (ACC) has emerged as a key brain region involved in pain processing (Bliss et al., 2016; Fuchs et al., 2014), and functional, structural and synaptic plasticity in the ACC is a fundamental mechanism to encode chronic pain information (Bliss et al., 2016). By utilizing mouse models of chronic pain, combined with electrophysiology, pharmacological manipulations, and optogenetic approaches, our goal is to elucidate the cellular and molecular mechanisms underlying dopamine-mediated synaptic plasticity alterations in the ACC associated with chronic pain. Through this multidisciplinary approach, this project aims to uncover novel insights into the neurobiology of chronic pain in ACC, with the ultimate goal of identifying new therapeutic strategies for alleviating pain and improving the quality of life for individuals suffering from this debilitating condition.