Our research bridges cellular and systems neuroscience with an emphasis on the mechanisms and effects of synaptic plasticity. We publish in some of the most important journals in the field including Science, Nature, Neuron, Nature Neuroscience, PNAS, and the Journal of Neuroscience. Or research leans heavily on live cell imaging of neurons both as a determinant of neuronal activity (Smetana et al Nat Neurosci. 2010 13:731-8) but also looking at ionic fluxes, synaptic vesicle turnover and dynamic protein-protein interactions at the level of synapses (Hamid et al J Neurosci. 2014 34:260-74) to determine pathways involved in synaptic plasticity. We utilize various approaches to live cell imaging of Ca2+ in synapses, axons and dendrites to relate this to both synaptic plasticity and behavior.

The principal foci of my research are twofold. To understand the mechanisms by which signal transduction pathways modulate neurotransmission and from there - behavior. We are particularly interested in how presynaptic mechanisms control synaptic transmission and how such modulatory mechanisms impact the neural control of behavior and motor output. The laboratory has been funded by the National Institutes of Neurological Disorders and Stroke (NINDS), the National Institutes of Mental Health (NIMH) and the National Science Foundation (NSF) for over 30 years. We also develop techniques utilizing simultaneous electrophysiology and live cell imaging in a number of cell compartments. In particular, we use the giant reticulospinal axons of lampreys as a model synapse to understand synaptic transmission and its plasticity in addition to the role it plays in descending motor control. A particular focus has been on the role that the G protein subunit Gbg plays in synaptic plasticity. We have recently demonstrated that this interacts with the SNARE complex fusion machinery in lamprey but also mammalian brain. The accessibility of lamprey presynaptic terminals to electrophysiological and imaging approaches, is further driving our need to utilize high temporal resolution imaging in lamprey giant synapses in combination with manipulations of protein constituents of the presynaptic terminal. These approaches allow the direct study of presynaptic protein-protein interactions involved with the physiology, but also pathologies involved in synaptic vesicle cycling.