Li, Yong-Xin and Xu, Youfeng and Ju, Donghong and Lester, Henry A. and Davidson, Norman and Schuman, Erin M. (1998) Expression of a dominant negative TrkB receptor, T1, reveals a requirement for presynaptic signaling in BDNF-induced synaptic potentiation in cultured hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America, 95 (18). pp. 10884-10889. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:LIYpnas98
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We have developed a method to analyze the relative contributions of pre- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using adenovirus-mediated gene transfer. A recombinant virus directed the expression of both a GFP reporter protein and TrkB.T1, a C-terminal truncated dominant negative TrkB neurotrophin receptor. When expressed in the presynaptic cell at synapses between embryonic hippocampal neurons in culture, the dominant negative TrkB.T1 inhibited two forms of synaptic potentiation induced by the neurotrophin brain-derived neurotrophic factor (BDNF): (i) greater evoked synaptic transmission and (ii) higher frequency of spontaneous miniature synaptic currents. These inhibition effects are not seen if the transgene is expressed only in the postsynaptic cell. We conclude that BDNF-TrkB signal transduction in the presynaptic terminal leads to both types of potentiation and is therefore the primary cause of synaptic enhancement by BDNF in these neurons.
|Additional Information:||Copyright © 1998 by the National Academy of Sciences. Contributed by Norman Davidson, July 10, 1998. We thank Dr. Andy Welcher (Amgen) for the generous gift of BDNF and TrkB antibody. We thank Sheri McKinney for tissue culture work. This work was supported by National Institutes of Health Grant MH-49176. E.M.S. is a Pew Biomedical Scholar, Beckman Young Investigator, Merck Scholar, and an Assistant Investigator of the Howard Hughes Medical Institute. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.|
|Subject Keywords:||LONG-TERM POTENTIATION, NEUROTROPHIC FACTOR, SILENT SYNAPSES, TYROSINE KINASE, PLASTICITY, LTP, TRANSMISSION, ENHANCEMENT, MICE|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||07 Nov 2005|
|Last Modified:||26 Dec 2012 08:41|
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