Stephen D. Meriney, Ph.D.
Associate Professor, Neuroscience- Ph.D. University of Connecticut (1986)
- Office: 461 Langley Hall
- Telephone:412-624-8283
- Fax:412-624-9198
- E-mail: meriney@pitt.edu
- Website:
Regulation and modulation of presynaptic ion channels and transmitter release.
Research Summary:
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. We are interested in the mechanisms that control calcium entry and how this entry triggers transmitter release. Calcium imaging experiments are compared with microelectrode recordings of the magnitude of transmitter release to aid in the interpretation of data collected.
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.
Modulation of N- and P/Q-type calcium channels expressed in cell lines. We have recently added the use of this model system to examine directly the gating and modulation of selective calcium channel subtypes stably expressed in cell lines. This allows us to study various forms of modulation in a model system where there are no other calcium channels expressed, and we can focus on studying in isolation the types of calcium channels that control transmitter release at many synapses.
Selected Publications:
Keith, R.K., Poage, R.E., Yokoyama, C.T., Catterall, W.A. and Meriney, S.D. Bidirectional modulation of transmitter release by calcium channel/syntaxin interactions in vivo. Journal of Neuroscience 27: 265-269, 2007.
Cho, S. and Meriney, S.D. The effects of presynaptic calcium channel modulation by roscovitine on transmitter release at the adult frog neuromuscular junction. European Journal of Neuroscience 23: 3200-3208, 2006.
King, J.D. and Meriney, S.D. Proportion of N-type calcium current activated by action potential stimuli. Journal of Neurophysiology 94: 3762-3770, 2005.
Wachman, E., Poage, R.E., Stiles, J.R., Farkas, D. and Meriney, S.D. Spatial distribution of calcium entry evoked by single action potentials within the presynaptic active zone. Journal of Neuroscience 24: 2877-2885, 2004.
Pattillo, J.M., Yazejian, B., DiGregorio, D.A., J. L. Vergara, Grinnell, A.D. and Meriney, S.D. Contribution of presynaptic calcium-activated potassium currents to transmitter release regulation in cultured Xenopus nerve-muscle synapses. Neuroscience 102: 229-240, 2001.