Our Research
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Neuron-Glial interactions in Health and Disease
Neuro-glial interactions are critical to understanding the intricate functioning of the central nervous system (CNS). Microglia, the resident immune cells of the brain, are central players in neuro-glial interactions and are critically involved in the maintenance of CNS health, immune responses, and synaptic plasticity. Their dysfunction is increasingly recognized as a key factor in the pathophysiology of a range of neurological diseases. Employing in vivo transgenic mouse models combined with imaging, molecular, behavioral, and pharmacological approaches, we aim to unravel the molecular and cellular mechanisms underlying epileptogenesis and provide insights for novel therapeutic targets.
A) Characterize the role of PNNs in epileptogenesis using novel SCN1a mouse model of Dravet syndrome
The significance of PNNs in regulating PV interneuron activity and synaptic plasticity have been critical for health and disease. ECM remodeling and PNN disruption is an integral part of epileptogenic changes. Yet, mechanistically, how these contribute to epileptogenesis remains unknown. With the advantage of the novel mouse model of SCN1a haploinsufficiency exclusively in the PV interneurons manifesting Dravet syndrome-like features would enable us to understand the function of ECM structures more precisely
B) Elucidate microglial regulation of perineuronal nets in the epileptic brain
Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround certain neurons, playing a crucial role in synaptic plasticity, neuronal stability, and the regulation of neural circuits. Under normal conditions, microglia help maintain the integrity of PNNs and support synaptic function. However, during injury or disease, microglia can influence the remodeling of PNNs, either by promoting their degradation or by altering their composition. This remodeling can impact neuronal plasticity and has been implicated in various neurological disorders, including epilepsy. Therefore, understanding the dynamic interaction between microglia and PNNs is critical for developing potential therapeutic strategies targeting neural circuit stability and plasticity.
C) Determine the role of PNNs in epilepsy associated behavioral comorbidities
Microglial activation and subsequent alterations to PNNs may contribute to impaired cognitive function and disease progression. The causal role of PNNs will be explored by adopting a battery of tests to assess epilepsy induced cognitive and social deficits, hyperactivity and anxiety-like behavior