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PMID: 10884321 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

TrkB receptor ligands promote activity-dependent inhibitory synaptogenesis.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 14 ·2000-07-15 ·Pages 5367-73

Seil FJ, Drake-Baumann R

Abstract

Organotypic cerebellar cultures derived from newborn mice were simultaneously exposed to activity-blocking agents and neurotrophins for 2 weeks. Activity-blocked explants treated with the TrkB receptor ligands BDNF and neurotrophin-4 (NT-4) developed a full complement of Purkinje cell inhibitory axosomatic synapses, as defined ultrastructurally, and displayed control spontaneous cortical discharge rates after recovery from activity blockade. Otherwise untreated activity-blocked cultures and activity-blocked cultures exposed to the TrkC receptor ligand NT-3 had reduced inhibitory synapse development and persistent cortical hyperactivity after recovery. The added TrkB receptor ligands did not induce axonal sprouting to account for increased inhibitory synaptogenesis. Addition of neurotrophins to untreated cerebellar cultures did not increase the complement of Purkinje cell axosomatic synapses. Exposure of cerebellar cultures to a combination of antibodies to BDNF and NT-4 resulted in reduced inhibitory synapse formation, similar to the effects of activity blockade, indicating the necessity for endogenous neurotrophins for development of the full complement of inhibitory synapses in the presence of neuronal activity. Application of antibodies to BDNF and NT-4 to cerebellar explants exposed to picrotoxin to increase neuronal activity prevented the hyperinnervation of Purkinje cell somata by inhibitory terminals characteristic of cultures exposed to picrotoxin alone. These results are consistent with the concept that TrkB receptor ligands promote inhibitory synaptogenesis. The ability of neurotrophins to substitute for neuronal activity in encouraging development of inhibitory synapses may have therapeutic implications.

MeSH Terms
Animals Animals, Newborn Antibodies, Blocking/pharmacology Axons/physiology Brain-Derived Neurotrophic Factor/antagonists & inhibitors,pharmacology Cells, Cultured Cerebellum/cytology,drug effects,growth & development GABA Antagonists/pharmacology Ligands Mice Nerve Growth Factors/antagonists & inhibitors,pharmacology Neural Inhibition/drug effects,physiology Neuroprotective Agents/pharmacology Organoids Picrotoxin/pharmacology Purkinje Cells/cytology,drug effects Receptor, trkB/metabolism Synapses/drug effects,physiology Tetrodotoxin/pharmacology
Chemicals
Antibodies, Blocking Brain-Derived Neurotrophic Factor GABA Antagonists Ligands Nerve Growth Factors Neuroprotective Agents Picrotoxin Tetrodotoxin Receptor, trkB neurotrophin 4
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Seil F J
Neurology Research, Veterans Affairs Medical Center and Departments of Neurology and Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201, USA. seilf@ohsu.edu
Drake-Baumann R
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Email
seilf@ohsu.edu
Published
2000-07-15
Pages
5367-73
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772333
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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