Grant: Master's Award: Canada Graduate Scholarships

Neural communication is carried out by the release of neurotransmitters which bind to postsynaptic ligand-gated ion channels to modulate neuronal activity. Dysregulated receptor expression has been linked to a constellation of disorders including schizophrenia, Parkinson's disease and Alzheimer's disease. As such, studies on ion channel physiology and dysfunction help facilitate diagnosis and treatment of many neurological disorders. My research focuses on nicotinic acetylcholine receptors (nAChRs), a class of ligand-gated ion channels that are activated by the transmitter acetylcholine (ACh). In the central nervous system (CNS), nAChRs are involved in sensorimotor processing and executive functions. However, their neurophysiological role in the CNS remains elusive. In a recent study using optogenetics, the Nashmi lab showed for the first time a subpopulation of dopaminergic (DA) neurons in the substantia nigra (SN) that received coreleased acetylcholine and GABA. Different probabilities of release and short-term adaptations were found for these two opposing transmitters. For my research project, I will study the neurotransmission properties between coreleased ACh and GABA mediated responses found on DA SN neurons. I will use electrophysiological experiments to test whether the differential probability of GABA versus ACh release is due to the difference in proximity of their respective vesicles from the influx of calcium necessary for vesicular release. I will also investigate mechanisms of short-term plasticity underlying ACh and GABA release using light stimulation with different concentrations of extracellular calcium and drugs targeting different calcium channel subtypes and GABA(B) receptors.