GluR- and TrkB-mediated maturation of GABA receptor function during the period of eye opening.
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 GABAAR alpha1 mRNA, whereas the level of alpha3 mRNA decreased. This result is consistent with the hypothesis that the IPSC kinetics of developing collicular neurons is determined by the level of alpha1/alpha3. As alpha1/alpha3 peaked when N-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 with bdnf-/- mice revealed that, with some delay, the increase of alpha1/alpha3 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 GABAAR gamma2L, as opposed to gamma2S. Together, these experiments suggest that the GABAAR alpha 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.
Henneberger
Christian
C
Sensory and Developmental Physiology, Johannes Mueller Centre for Physiology, University Medicine (Charité), Tucholskystr. 2, D-10117 Berlin, Germany.
Jüttner
René
R
Schmidt
Sonja A
SA
Walter
Jan
J
Meier
Jochen C
JC
Rothe
Thomas
T
Grantyn
Rosemarie
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004622:Embryo, Mammalian; D005123:Eye / Q000254:growth & development*; D018755:GABA Agonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013477:Superior Colliculi / Q000166:cytology / Q000254:growth & development; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077334:Zolpidem
D019208:Brain-Derived Neurotrophic Factor; D018755:GABA Agonists; D011725:Pyridines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C056639:2-amino-5-phosphopentanoic acid; D000077334:Zolpidem; D020813:Receptor, trkB; D014633:Valine