Susana Cohen-CoryAssociate Professor, Neurobiology and Behavior |
|
|
Research Interests |
Synapse formation in the developing nervous system; in vivo imaging studies | |
| URL | home page | |
|
Research Abstract |
Over the years, a major focus of our research has been to elucidate events that guide the development of synaptic connectivity in the living brain. The approach that we use is to image neurons in intact, non-mammalian vertebrate embryos as a means to provide new insight into the cellular, molecular, and activity-dependent processes that guide synaptogenesis in the central nervous system. Xenopus laevis tadpoles offer a uniquely accessible model system in which dynamic events can be studied because of the translucency of the embryos and because of their accessibility to experimental manipulation. The Xenopus visual system has provided us with a unique model system to study the molecular basis of developmental connectivity in vivo. In vivo time-lapse imaging studies from our laboratory have demonstrated that a process of iterative formation and elimination of synapses and neuronal branches guides synaptogenesis and is responsible for the selective stabilization of those synapses that are maintained during development. We have also used the Xenopus visual system as a model to demonstrate that the neurotrophin brain-derived neurotrophic factor (BDNF) influences synapse formation and synapse stabilization in central neurons in vivo. BDNF is a potent modulator of multiple aspects of brain development and is involved in the control of synaptic function in most vertebrate species. The work performed in my laboratory during the last couple of years has further established key mechanisms by which BDNF controls the development of retinotectal synaptic connectivity. Our work established that BDNF acts cell-autonomously, specifically on presynaptic retinal neurons to; 1) control the transition from growth cone morphology to branching axons, 2) control the stability of axon branches and synapses, and 3) control synaptic function by controlling the ultrastructural composition of synapses and the synaptic vesicle pool. Moreover, we have recently demonstrated that in the retinotectal system, BDNF acts presynaptically but has secondary effects on postsynaptic neurons. Specifically, our studies demonstrate that BDNF has an indirect influence on the morphology and synaptic connectivity of tectal neurons, the postsynaptic targets of retinal ganglion cells (RGCs), and that these effects are delayed with respect to those on RGC axons. In addition, our time-lapse imaging studies show that the dynamic behavior of tectal neuron dendritic arbors (as well as synapse dynamics) parallels the behavior of RGC axons under normal conditions and that this process is suceptible to alterations in glutamate receptor function. Thus, by using the visual system of Xenopus tadpoles as an in vivo model our group has provided unique evidence on how dynamic is synapse formation and stabilization and has demonstrated both permissive and instructive roles for BDNF during synaptogenesis in living embryos. Current studies are aimed at elucidating potential molecular interactions between neurotrophins and extracellular guidance molecules that control synaptogenesis in the developing brain, and the signaling mechanisms that are used to modulate both the morphological and synaptic complexity of developing neurons. By studying how developmental molecular signals interact to control the structural and functional plasticity of the developing brain we aim to provide valuable insights into fundamental mechanisms of synaptogenesis, and to advance the understanding of development deficiencies can affect brain function. |
|
| Publications | C.Manitt, A.M. Nikolakopoulou, D. Almario, S. Nguyen, and S. Cohen-Cory. Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain. Journal of Neuroscience, 29; 11065-11077, 2009. | |
| S. Marshak, A.M. Nikolakopoulou, R. Dirks, G.J.M. Martens and S. Cohen-Cory. Cell autonomous TrkB signaling in presynaptic retinal ganglion cells mediates axon arbor growth and synapse maturation during the establishment of retinotectal synaptic connectivity. Journal of Neuroscience, 27, 2444-2456, 2007. | ||
| A.L. Sanchez, B.J. Matthews, M.M. Meynard, B. Hu, S. Javed and S. Cohen-Cory. BDNF increases synapse density in dendrites of developing tectal neurons in vivo. Development, 133, 2477-2486, 2006. | ||
| B. Hu, A. M Nikolakopoulou and S. Cohen-Cory. BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo. Development, 132, 4285-4298, 2005. | ||
| S. Cohen-Cory and B. Lom. Neurotrophic Regulation of Retinal Ganglion Cell Synaptic Connectivity: From Axons and Dendrites to Synapses. International Journal of Developmental Biology, 48; 947-956, 2004. | ||
| N. Prakash, S. Cohen-Cory, S. Penshuk, R. Frostig. The basal forebrain cholinergic system is involved in rapid nerve growth factor (NGF)-induced plasticity in the barrel cortex of adult rats. Journal of Neurophysiology, 91; 424-37, 2004. | ||
| T.S.Tran, S. Cohen-Cory, and P.E. Phelps. Embryonic GABAergic Spinal Commissural Neurons Project Rostrally To Mesencephalic Targets. Journal of Comparative Neurology, 475; 327-339, 2004. | ||
| S. Cohen-Cory. The developing synapse: construction and modulation of synaptic structure and circuits. Science 298; 770-776, 2002. | ||
| B. Lom, J. Cogen, A. Lontok Sanchez, T. Vu, and S. Cohen-Cory. Local and target-derived BDNF exert opposing effects on the dendritic arborization of retinal ganglion cells in vivo. Journal of Neuroscience 22; 7639-49, 2002. | ||
| B. Alsina, T. Vu and S. Cohen-Cory. Visualizing Synapse Formation in Arborizing Optic Axons in vivo: Dynamics and Modulation by BDNF. Nature Neuroscience, 4; 1093-101, 2001. | ||
| J. Cogen and S. Cohen-Cory. Nitric oxide modulates retinal ganglion cell axon arbor remodeling in vivo. Journal of Neurobiology 45; 120-133, 2000. | ||
| N. Prakash, P. Vanderhaeghen, S. Cohen-Cory, J. Frisén, J. G. Flanagan, and R. D. Frostig. Malformation of the functional cortical somatosensory map in adult ephrin-A5 knockout mice revealed by in vivo functional imaging. Journal of Neuroscience 20; 5841-5847, 2000. | ||
| B. Lom and S. Cohen-Cory. BDNF differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo. Journal of Neuroscience, 19; 9928-9938, 1999. | ||
| S. Cohen-Cory. BDNF modulates, but does not mediate, activity-dependent branching and remodeling of optic axon arbors in vivo. Journal of Neuroscience 19; 9996-10003, 1999. | ||
| S. Cohen-Cory, E. Escandón and S.E. Fraser. The cellular patterns of BDNF and trkB expression suggest multiple roles for BDNF during Xenopus visual system development. Developmental Biology, 179, 102-115 1996. | ||
| N. Prakash, S. Cohen-Cory and R.D. Frostig. Rapid and opposite effects of BDNF and NGF on the functional organization of the adult cortex in vivo. Nature 381, 702-706, 1996. | ||
| S. Cohen-Cory and S.E. Fraser. Effects of brain-derived neurotrophic factor on optic axon branching and remodeling in vivo. Nature 378, 192-196, 1995. | ||
| S. Cohen-Cory and S.E. Fraser. BDNF in the development of the visual system of Xenopus. Neuron 12; 747-761, 1994. | ||
| Graduate Programs |
Neurobiology and Behavior |
|
| Research Center | Member, Developmental Biology Center | |
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=4922 | |
| Last updated | 10/26/2009 | |