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PMID: 11850459 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 4 ·2002-02-15 ·Pages 1316-27

Carter AR, Chen C, Schwartz PM, Segal RA

Abstract

Neurotrophins are key regulators of neuronal survival and function. Here we show that TrkB, the receptor for brain-derived neurotrophic factor (BDNF), is located at parallel fiber to Purkinje cell (PF/PC) synapses of the cerebellum. To determine the effects of TrkB receptor activation on synapse formation and function, we examined the parallel fiber to Purkinje cell synapses of mice with a targeted deletion of the BDNF gene. Although Purkinje cell dendrites are abnormal in BDNF -/- mice, PF/PC synapses are still able to form. Immunohistochemical analysis of mutant animals revealed the formation of numerous PF/PC synapses with the appropriate apposition of presynaptic and postsynaptic proteins. These synapses are functional, and no differences were detected in the waveform of evoked EPSCs, the amplitude of spontaneous mini-EPSCs, or the response to prolonged 10 Hz stimulus trains. However, paired-pulse facilitation, a form of short-term plasticity, is significantly decreased in BDNF -/- mice. Detailed ultrastructural analysis of the presynaptic terminals demonstrated that this change in synaptic function is accompanied by an increase in the total number of synaptic vesicles in mutant mice and a decrease in the proportion of vesicles that are docked. These data suggest that BDNF regulates both the mechanisms that underlie short-term synaptic plasticity and the steady-state relationship between different vesicle pools within the terminal.

MeSH Terms
Animals Brain-Derived Neurotrophic Factor/deficiency,genetics,metabolism,pharmacology Calbindins Cerebellum/cytology,metabolism Dendrites/ultrastructure Electric Stimulation Excitatory Postsynaptic Potentials/physiology Gene Deletion In Vitro Techniques Mice Mice, Knockout Mice, Mutant Strains Neuronal Plasticity/drug effects,physiology Patch-Clamp Techniques Presynaptic Terminals/drug effects,metabolism,ultrastructure Purkinje Cells/metabolism,ultrastructure Receptor, trkB/metabolism Receptors, Glutamate/metabolism S100 Calcium Binding Protein G/metabolism Synapses/drug effects,metabolism,ultrastructure Synaptic Transmission/physiology Synaptic Vesicles/ultrastructure
Chemicals
Brain-Derived Neurotrophic Factor Calbindins Receptors, Glutamate S100 Calcium Binding Protein G glutamate receptor delta 2 Receptor, trkB
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Carter Alexandre R
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Chen Chinfei
Schwartz Phillip M
Segal Rosalind A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2002-02-15
Pages
1316-27
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6757568
Subset
IM
Grants
NLM NIH HHS · F31 LM000040 · United States
NINDS NIH HHS · R01 NS037757 · United States
NINDS NIH HHS · NS37757 · United States
NLM NIH HHS · 5F31LM00040-05 · United States
External Links
PubMed source PMC Full Text View journal details
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