The Journal of Neuroscience, October 1, 1998, 18(19):7941-7952
Functional Change of NMDA Receptors Related to Enhancement of
Susceptibility to Neurotoxicity in the Developing Pontine Nucleus
Akira
Mitani1,
Masahiko
Watanabe2, and
Kiyoshi
Kataoka1
1 Department of Physiology, School of Medicine, Ehime
University, Shigenobu, Onsen-gun, Ehime 791-0295, Japan, and
2 Department of Anatomy, Hokkaido University School of
Medicine, Sapporo 060-8638, Japan
The developing neurons have been reported to be extremely
susceptible to toxicity of NMDA during a restricted developmental period. Pontosubicular neuronal necrosis is a typical type of perinatal
human brain lesion and often coexists with other forms of cerebral
hypoxic and ischemic injuries. To determine whether functional changes
of NMDA receptors related to the susceptibility to NMDA toxicity are
involved in developing neurons in the pontine nucleus, we have examined
the lesion produced by in vivo direct injection of NMDA
into the pontine nucleus of rats at postnatal days 1-30, recorded
NMDA-induced whole-cell currents from neurons in the pontine nucleus in
the developing rat brainstem slices, and performed in
situ hybridization for NMDA receptor subunit mRNAs in the
pontine nucleus. The susceptibility to NMDA neurotoxicity peaked near
postnatal day 15, and the NMDA-induced currents showed prominent
reduction of the voltage-dependent block by Mg2+
near postnatal day 15. The pontine nucleus near postnatal day 15 showed
distinct expression of the NMDA receptor subunit NR2C mRNA. These
results suggest that the susceptibility to NMDA neurotoxicity that is
enhanced in the rat pontine nucleus near postnatal day 15 is mediated
by the NMDA receptor channels that are relatively insensitive to
Mg2+ and that the reduction in the sensitivity of
NMDA receptors to Mg2+ correlates with the
expression of the NR2C. We present the possibility that functional
changes in the NMDA receptor channels play a crucial role in the
occurrence of developmentally specific neuronal injury.
Key words:
NMDA receptor; pontine nucleus; development; neurotoxicity; slice patch clamp; Mg2+ block; in situ hybridization; NR2 subunits
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197941-12$05.00/0
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