Dr. Mani Ramaswami
Neural circuit function, plasticity, and maintenance
In trying to map brain activity to innate and learned behaviours, the greatest advances have been made by "sizing down" the problem: probing simple model animals such as the tiny fruit-fly, Drosophila. One of Drosophila's most informative behaviours has been, surprisingly, olfaction. Smell is detected by frontline olfactory neurons, which connect to brain centres that process olfactory signals. The early olfactory system has an exquisitely precise and broadly conserved architecture, revealed in part through pioneering work from our colleague and collaborator, Veronica Rodrigues. We collaborate with K. VijayRaghavan's group, to use the sophisticated knowledge and access to the olfactory system to dissect mechanisms of a simple olfactory memory called olfactory habituation on a multitude of fronts. We are mapping contributions of individual neuronal types (e.g. wide-field inhibitory and neuromodulatory interneurons) and synaptic plasticity mechanisms in circuit plasticity that underlies habituation. We are also studying how translational control of synaptic mRNAs, potentially through regulated prion-domain mediated assembly and disassembly of mRNA-protein complexes, contributes to a long-lasting form of olfactory habituation. The latter is of additional interest, because mutations that alter mRNP assembly in vivo, appear to underlie various synaptopathies and neurodegenerative diseases in humans. With a readily available stock of mutant genes, reagents provided by an exciting genome resources being built in C-CAMP, and in vivo brain imaging techniques established in my lab in Trinity College, Dublin, we are now a good way into reconstructing the highly integrated and hitherto mysterious process of behavioral habituation, whose secrets are already helping us to understand principles of neural circuit plasticity and learning throughout the animal kingdom.