Organisms interact with their immediate environment, including members of their own and different species, through a number of sensory modalities. The dynamic interplay between the sensory environment, genes and neural circuits that occurs in evolutionary and developmental time shapes the sensory biology of an animal, which we hope to understand at various levels.
Rodents and several animals depend on their highly elaborate sense of smell to find food, social interactions and detect predators. Our current studies use the mouse vomeronasal (also termed accessory olfactory) system as a model to study the molecular and cellular mechanisms, gene expression patterns that have evolved to detect specialized chemo-signals in sensory neurons and their transmission to the brain to elicit innate behaviors. Recently using single cell and spatial transcriptomics, we have delineated gene expression patterns associated with the developmental specification of neuronal subtypes (available at: scvnoexplorer). These data form the base for mechanistic investigations to understand molecular mechanisms that enable sensory detection in neurons. For instance our research has uncovered a unique endoplasmic reticulum environment that diverges during neuronal development.
In a second set of projects, we build on our long standing interest to investigate the structure and plasticity of neuronal synapses at nanometer scale resolution, by developing the tools of single molecule super-resolution microscopy. We have been interested in asking the broad question: how does sensory experience sculpt the properties of synapses? At single synapse resolution, we investigate synapses in peripheral sensory neurons as well as higher order centres in the brain, where these signals are processed. Our current focus has been on the auditory system, where we are investigating the transformation of synapses in the cochlea and auditory cortex, upon exposure to sound. We hope that these studies will also lead to a better understanding of congenital deafness, occupational hearing loss and their effective treatment.
Extending our studies of neuronal synapses and gene expression patterns, our lab has embarked on clinical collaborative projects to understand the synaptic basis of psychiatric disorders. Our current focus is on Bipolar disorder, a major psychiatric illness characterized by alterations in mood, activity and thoughts during episodes of depression and mania. Alterations in levels of neurotransmitters dopamine, glutamate and their synaptic receptors is hypothesized to underlie the pathophysiology of psychiatric illness as well as the response or resistance to treatments and their side-effects. Whether treatment should be restricted to episodes or will need to be lifelong cannot be predicted, primarily due to the poor understanding of underlying neurobiological changes.
Using mouse models that phenocopy the human condition, we aim to quantitatively study the changes in dendritic spines and neurotransmitter receptors at single synapse, nanoscale resolution. Using standard interventions used for treating human patients, we hope to understand whether a pathologic state of synaptic receptors can be reversed and we hope to map gene expression patterns in the brain associated with the treatments.
These studies have implications to the choice of medicines prescribed, their mechanism of action, prognosis and whether clinical remission is the same as neurobiological remission, as studied at the synapse. We hope the pipeline thus created would enable investigation into other psychiatric conditions such as depression and schizophrenia.