PhD research

We are investigating the molecular organization of trans-synaptic nano-columns and their role in signal computation and plasticity in glutamatergic synapses. Glutamatergic synapses form the bulk of excitatory synapses in the Central Nervous System and are important for many aspects of behaviour and cognition. Dysregulation of glutamatergic synapses is one of the main causes of neurodevelopmental and neurodegenerative disorders. Most often the postsynaptic organization at the glutamatergic synapses is impaired in these conditions. This makes it imperative to understand the fundamental mechanisms of synaptic transmission.

Synaptic transmission is the spatiotemporally coordinated sequence of biochemical events resulting in the transfer of chemical information between neurons. At an excitatory synapse, depolarization of the presynaptic neuron results in the opening of voltage-gated calcium channels at the axon terminal, allowing calcium influx. Subsequently, calcium sensors facilitate the fusion of vesicles and the release of neurotransmitters into the synaptic cleft. This neurotransmitter, binds to surface receptors at the post synapse. Various advanced microscopy techniques have shown that these receptors are not distributed homogeneously throughout the synaptic membrane. Rather they form dynamic clusters called nanodomains facilitated by scaffold proteins like PSD95, SAP97, Homer, Shank etc. In the postsynaptic compartment, the scaffold proteins exist in two fractions - membrane-bound and freely diffusing. Our goal is to investigate the contribution of these fractions in the organization and dynamics of surface receptors.