Stephen D. Meriney Associate Professor, Neuroscience University of Pittsburgh Email: meriney@bns.pitt.edu Lab Website: http://www.pitt.edu/~neurosci/merineylab/meriney.html

Research Interests Our research program focuses on studying mechanisms that control synaptic plasticity in the nervous system. We use several model systems that provide the opportunity to study these mechanisms directly. In particular, we are interested in those events that occur in nerve terminals to regulate or modulate synaptic transmission. Calcium imaging in nerve terminals. We use high-resolution calcium imaging in adult nerve terminals to examine the characteristics and modulation of the calcium entry that control transmitter release at the synapse. We have developed a method for imaging the spatial distribution of calcium entry following a single action potential stimulus. Using this approach, we have provided evidence that a very small subset of the available calcium channels opens in the nerve terminal with each stimulus. We hypothesize that transmitter release is triggered by the opening of single calcium channels in these nerve terminals and have begun to study the modulation of this process. The direct study of nerve terminals. Nerve terminals are studied directly using a preparation of Xenopus spinal neurons that will form large presynaptic nerve terminals on muscle cells in culture. This culture system is well suited for direct study of the presynaptic nerve terminal because these terminals form and mature very quickly (< 1 day in vitro), and are accessible to direct study using patch clamp electrophysiological techniques. Using this preparation we currently are interested in how presynaptic calcium channels are modulated by syntaxin interactions, and what role L-type calcium channels have at these synapses. Modulation of nerve terminal function in vivo. We have also begun to study the function of nerve terminals as they mature in vivo. Using the developing Xenopus tadpole tail neuromuscular junction we are examining the effects of manipulating calcium channel-SNARE protein interactions. Modulation of calcium channels in neurons. Another major focus of study in the lab centers around the modulation of calcium channels in parasympathetic neurons. Neuropeptide-mediated modulation of ion channels in the nerve terminal represents a major mechanism for modulation of synaptic transmission. To examine the intracellular mechanisms that mediate these modulatory events, we use acutely dissociated parasympathetic neurons because they are potently modulated by peptides and are amenable to the types of experimental manipulation that has revealed interesting details of intracellular signal transduction cascades. Here, we are currently using cell bodies as a model system with which to study the signal transduction cascade that couples somatostatin receptors to the modulation of calcium current and transmitter release. Using this approach, details of calcium channel modulation can be elucidated. These studies include using action potential waveforms as voltage-clamp commands to study calcium current modulation under normal activation conditions. Modulation of synaptic transmission in rat hippocampal cultured neurons. We have recently added the use of this model system to examine the functional significance of calcium channel-SNARE protein manipulations using transfection with various experimental reagents. Using this approach we measure synaptic transmission at autapses and calcium influx into presynaptic sites using imaging techniques. Recent Publications Artim, D.E. and Meriney. S.D. G-protein-modulated Ca2+ current with slowed activation does not alter the kinetics of action potential-evoked Ca2+ current. Journal of Neurophysiology 84: 2417-2425, 2000. Pattillo, J.M., Yazejian, B., DiGregorio, D.A. J., Vergara, L., Grinnell, A. D. &. Meriney, S. D. ontribution of presynaptic calcium-activated potassium currents to tra nsmitter release regulation in cultured Xenopus nerve-muscle synapses. Neuroscience 102: 229-240. (2001). Choh, V., Sivak, J.G., Meriney, S.D. A physiological model to measure effects of age on lenticular accommodation and spherical aberration in chickens. Investigative Ophthalmology and Visual Science. 43(1): 92-8, 2002. Poage, R.E., Meriney, S.D. Presynaptic calcium influx, neurotransmitter release, and neuromuscular disease. Physiology and Behavior. 77(4-5): 507-12, 2002. Wachman, E.S., Poage, R.E., Stiles, J.R., Farkas, D.L., Meriney, S.D. Spatial distribution of calcium entry evoked by single action potentials within the presynaptic active zone. Journal of Neuroscience. 24(12): 2877-85, 2004.