Article abstract
Nature Neuroscience 12, 767 - 776 (2009)
Published online: 17 May 2009 | Corrected online: 28 May 2009 | doi:10.1038/nn.2315
Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release
Camin Dean1,2, Huisheng Liu1,2, F Mark Dunning1,2, Payne Y Chang1, Meyer B Jackson1 & Edwin R Chapman1,2
Abstract
Synaptotagmin-IV (syt-IV) is a membrane trafficking protein that influences learning and memory, but its localization and role in synaptic function remain unclear. We found that syt-IV localized to brain-derived neurotrophic factor (BDNF)-containing vesicles in hippocampal neurons. Syt-IV/BDNF–harboring vesicles underwent exocytosis in both axons and dendrites, and syt-IV inhibited BDNF release at both sites. Knockout of syt-IV increased, and overexpression decreased, the rate of synaptic vesicle exocytosis from presynaptic terminals indirectly via changes in postsynaptic release of BDNF. Thus, postsynaptic syt-IV regulates the trans-synaptic action of BDNF to control presynaptic vesicle dynamics. Furthermore, selective loss of presynaptic syt-IV increased spontaneous quantal release, whereas a loss of postsynaptic syt-IV increased quantal amplitude. Finally, syt-IV knockout mice showed enhanced long-term potentiation (LTP), which depended entirely on disinhibition of BDNF release. Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP.
- Department of Physiology, University of Wisconsin, Madison, Wisconsin, USA.
- Howard Hughes Medical Institute, University of Wisconsin, Madison, Wisconsin, USA.
Correspondence to: Edwin R Chapman1,2 e-mail: chapman@physiology.wisc.edu
Correspondence to: Camin Dean1,2 e-mail: camin@physiology.wisc.edu
