The decline in synaptic GluN2B and rise in inhibitory neurotransmission determine the end of a critical period.
Neuronal plasticity is especially active in the young, during short windows of time termed critical periods, and loss of a critical period leads to functional limitations in the adults. The mechanism that governs the length of critical periods remains unknown. Here we show that levels of the NMDA receptor GluN2B subunit, which functions as a Ca2+channel, declines in spinal cord synapses toward the end of the critical period for activity-dependent corticospinal synapse elimination. This period could be prolonged by blocking the decline of GluN2B, and after its termination the critical period could be reopened through upregulation of GluN2B. It is known that inhibitory neural activity increases with development in the CNS including the spinal cord. Suppression of the increasing inhibitory activity using low-dose strychnine also prolonged this critical period. During the strychnine-widened time window, Ca2+influx through GluN2B channels returned to a level comparable to that seen during the critical period, though the level of GluN2B was slightly reduced. These findings indicate that loss of GluN2B subunits and the associated reduction in Ca2+influx determines the end of the critical period in our in vitro CS system.
Department of Physiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Noriko
N
Isoo
Department of Physiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Takae
T
Ohno
Department of Physiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Mutsumi
M
Isowaki
Department of Physiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Satoshi
S
Fukuda
Department of Physiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Naoyuki
N
Murabe
Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimono, Tochigi 329-0498, Japan.
Hiroaki
H
Mizukami
Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimono, Tochigi 329-0498, Japan.|Division of Genetic Therapeutics, the Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Keiya
K
Ozawa
Department of Molecular Neurobiology &Pharmacology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.|Brain Science Laboratory, The Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.
Masayoshi
M
Mishina
Department of Physiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Masaki
M
Sakurai
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