Coordinated changes in dendritic arborization and synaptic strength during neural circuit development.
Neural circuit development requires concurrent morphological and functional changes. Here, we identify coordinated and inversely correlated changes in dendritic morphology and mEPSC amplitude following increased neural activity. We show that overexpression of beta-catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mEPSC amplitudes, while postsynaptic expression of a protein that sequesters beta-catenin reverses the effects of activity on reducing mEPSC amplitudes. These results were confirmed immunocytochemically as changes in the size and density of surface synaptic AMPA receptor clusters. In individual neurons there was an inverse linear relationship between total dendritic length and average mEPSC amplitude. Importantly, beta-catenin overexpression in vivo promoted dendritic growth and reduced mEPSC amplitudes. Together, these results demonstrate that coordinated changes in dendritic morphology and unitary excitatory synaptic strength may serve as an important intrinsic mechanism that helps prevent neurons from overexcitation during neural circuit development.
Peng
Yi-Rong
YR
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
He
Shan
S
Marie
Helene
H
Zeng
Si-Yu
SY
Ma
Jun
J
Tan
Zhu-Jun
ZJ
Lee
Soo Yeun
SY
Malenka
Robert C
RC
Yu
Xiang
X
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009415:Nerve Net / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; D051176:beta Catenin; D013779:Tetrodotoxin