Activity-dependent synaptic plasticity during
neural development, using neuromuscular and CNS synapses in mice
and zebrafish as model systems; neurotrophic and other cell-cell
signaling mechanisms underlying synapse formation and maintenance;
axon outgrowth and synapse reinnervation after neural injury.
Molecular
and cellular biology; electrophysiology; in vivo imaging in mice
and zebrafish; confocal microscopy.
We are studying the cellular and molecular interactions between
neurons and their targets that underlie synapse formation and
maintenance during neural development. We use neuromuscular synapses
between motor neurons and muscle fibers in mice and zebrafish
in vivo, and CNS synapses among hippocampal neurons in vitro,
as relatively simple, accessible and easily manipulated model
systems. Imaging and electrophysiology are used to study how synaptic
structure and function are affected by neural activity in mice
and zebrafish. Cre/lox genetic deletion strategies are used to
study neurotrophin signaling mechanisms that underlie synapse
formation, maintenance and axon regeneration in mice. Cellular,
molecular and genetic approaches are used to dissect the mechanisms
underlying synapse formation in wild type and mutant zebrafish.
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Neuromuscular synapses from adult mouse muscle. Immunostained presynaptic nerve terminals in green, perisynaptic Schwnan cells in blue, postsynaptic AChR clusters in red. Ryan Wyatt, Dr. Srilatha Potluri, Dr. Elizabeth Vernon Pitts and Huan Ying Zhou use this model system to study the roles of activity and neurotrophic interactions that underlie synapse formation, function and reinnervation after injury.
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Hippocampal synapses in vitro. Immunostained neuron with presynaptic nerve terminals (green) and postsynaptic NMDA receptor clusters (red) impinging on its dendritic arbor. Ethan Hughes and Solsire Zevallos study the role of astrocytes and neurotrophic signaling during synaptogenesis using this model system.
Neuromuscular synapses in wild type zebrafish at 48 hours of development. Externally, very early stages in synaptogenesis are accessible, unlike in mice. Immunostained presynaptic nerve terminals (green) apposed to postsynaptic AChR clusters (red) on developing muscle fibers. Yuanquan Song, Marion Scott, and Amy Kugath study mutant zebrafish that have defects in various aspects of neuromuscular synaptogenesis.
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KEY
WORDS: Synaptogenesis; synaptic plasticity; activity;
neuromuscular junction; motor neuron; neurotrophins; neuromuscular
disease; mice; zebrafish
Personius, K. E. and Balice-Gordon, R. J. (2001) Loss of correlated motor neuron activity during synaptic competition at developing neuromuscular synapses. Neuron 31: 395-408.
Elmariah, S. B. and Balice-Gordon, R. J. (2004) Postsynaptic TrkB-mediated signaling modulates NMDA clustering at synapses via a homeostatic, activity-dependent mechanism. J. Neurosci. 24: 2380-2393.
Elmariah, S. B., Oh, E. J., Hughes, E. and Balice-Gordon, R. J. (2005) Astrocytes regulate inhibitory synapse formation via Trk-mediated modulation of postsynaptic GABA A receptors. J. Neuroscience 25: 3638-3650. (This paper was featured in “This Week in the Journal” in J. Neurosci ., and in “Research Highlights” in Nature , 04-30-05 issue).
Panzer, J. A., Gibbs, S. M., Dosch, R., Wagner, D., Mullins, M. C., Granato, M. and Balice-Gordon, R. J. (2005) Neuromuscular synaptogenesis in wild type and mutant zebrafish. Developmental Biology285: 340-357.
Panzer, J.A., Gibbs, S., Song, Y., and Balice-Gordon, R.J. (2006) In vivo imaging of preferential motor axon outgrowth to and synaptogenesis at prepatterned acetylcholine receptor clusters in embryonic zebrafish skeletal muscle. J. Neuroscience 26: 934-947.
Front row left to right: Rita Balice-Gordon, Ethan Hughes, Ryan Wyatt, Elizabeth Vernon Pitts, Srilatha Potlui, Sara Gibbs, Xiaoyu Peng
Back row left to right: Marion Scott, Darren Hess, Amy Kugath, Yuanquan Song, Cristin Welle, Paul Scherer
