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- Title
GluR- and TrkB-mediated maturation of GABA<sub>A</sub> receptor function during the period of eye opening.
- Authors
Henneberger, Christian; Jüttner, René; Schmidt, Sonja A.; Walter, Jan; Meier, Jochen C.; Rothe, Thomas; Grantyn, Rosemarie
- Abstract
Synapse maturation includes the shortening of postsynaptic currents, due to changes in the subunit composition of respective transmitter receptors. Patch clamp experiments revealed that GABAergic inhibitory postsynaptic currents (ISPCs) of superior colliculus neurons significantly shorten from postnatal day (P)1 to P21. The change started after P6 and was steepest between P12 and P15, i.e. around eye opening. It was accompanied by enhanced sensitivity to zolpidem and increased expression of GABAARα1 mRNA, whereas the level ofα3 mRNA decreased. This result is consistent with the hypothesis that the IPSC kinetics of developing collicular neurons is determined by the level ofα1/α3. Asα1/α3 peaked whenN-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents reached their maximum (P12) it was asked whether NMDAR activity can shape the kinetics of GABAergic IPSCs. Cultured collicular neurons were treated with NMDA or NMDAR block, and it was found that the former resulted in faster and the latter in slower IPSC decay. Group I mGluR blockade had no effect. Experiments withbdnf –/– mice revealed that, with some delay, the increase ofα1/α3 mRNA also occurred in the chronic absence of brain-derived neurotrophic factor (BDNF) and, again, this was accompanied by the shortening of IPSCs. In addition, there was an age-dependent depression of IPSC amplitudes by endogenous BDNF, which might reflect the developmental increase in the expression of GABAARγ2L, as opposed toγ2S. Together, these experiments suggest that the GABAARα subunit switch and the associated change in the IPSC kinetics were specifically controlled by NMDAR activity and independent on the signalling through group I mGluRs or TrkB.
- Subjects
SYNAPSES; NEURAL transmission; GABA; NERVOUS system; MESSENGER RNA; AMINO acid neurotransmitters
- Publication
European Journal of Neuroscience, 2005, Vol 21, Issue 2, p431
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2005.03869.x