Our recent work has demonstrated that reducing InsP3R function in Drosophila neurons affects feeding and growth in larvae and multiple aspects of flight circuit development and function in pupae and adults(Read here). These studies have shown that restoring InsP3R function in neurons which either synthesize monoamines (like dopamine) or insulin-like peptides (ILPs) rescues InsP3R mutant defects.

More recently, projects to understand how InsP3R mutants respond to changes in regulation of intracellular store Ca2+ and to stress conditions (Subramanian et.al 2013) have been initiated. Work from my group has demonstrated for the first time in a physiological context the requirement for store-operated calcium entry downstream of InsP3 signaling in neurons. Results from these studies suggest that genetic and pharmacological methods could be used for controlling intracellular Ca2+ homeostasis as a possible therapeutic strategy in certain neurodegenerative and metabolic diseases. Drosophila model and human studies in the context of such diseases are in progress.

A model of existing and proposed pathways that contribute to spontaneous Ca2+ spikes and excitability in neurons.