Presynaptic processes

Presynaptic terminal is seen very often as just an on-off faucet as most studies focus on the postsynaptic responses.This over-simplification arises due to experimental difficulty in making direct measurements at the presynaptic terminal. It is also difficult to delineate the specific contribution of the presynaptic terminal based on postsynaptic activity alone. We counter this by building physiologically realistic spatially explicit models of the presynaptic terminal that will direct experiments and vice versa to address gaps in our understanding.
We study how different sources of calcium modulate spatiotemporal details of the local calcium signal in the presynaptic terminal and influence vesicle release and Short-term plasticity (STP). We ask how different forms of STP impacts information during synaptic transmission and regulate energy use.
We investigate mechanisms of Long-term potentiation (LTP) at the CA3 presynaptic terminal of the hippocampus and the signaling involved neurotransmitter vesicle recycling. The number of vesicles available for release in the readily releasable pool of small hippocampal synapses are small and can be a bottleneck during intense activity. However activity is also seen to change this number and modulate vesicle recycling time on 'as per need' bases. As a LTP mechanism, we seek to create quantitative models for 1) activity dependent vesicle recycling and 2) different forms vesicles fusion that can switch from full fusion, where vesicle membrane looses its identity, to kiss-and-run that allows vesicle membranes to retain its identity and refill neurotransmitter rapidly. LTP mediated changes that structurally remodel the postsynaptic terminal also go hand-in-hand with presynaptic remodeling. We seek to understand how presynaptic structural changes, in turn, modify synaptic dynamics.
A diverse morphology of presynaptic terminals that range from a single release site to several hundred release sites, presence or absence of endoplasmic terminal and mitochondria is observed across brain areas and within the hippocampus. We examine in detail, structure-function relationships at the presynaptic terminal and its downstream effects on postsynaptic plasticity.
A presynaptic locus has been identified in several neurological disorders. We specifically aim to understand changes in calcium signaling leading upto calcium overload associated with Alzheimer's Disease (AD). We ask how differential localiztion of proteins in presynaptic terminal seen diseases can adversely affect function.