GABAC receptor subunit mRNA expression in the rat superior colliculus is regulated by calcium channels, neurotrophins, and GABAC receptor activity.
The distribution of mRNA for the rho2 subunit of the GABA(C) receptor is much broader in organotypic SC cultures than in vivo, suggesting that GABA(C) receptor expression is regulated by environmental factors. Electrophysiological recordings indicate that neurons in SC cultures have functional GABA(C) receptors, although these receptors exhibited smaller conductance than in vivo, probably due to increased rho2 subunit expression. Adding cortical input, treatment with various neuromodulators, and blocking neuronal activity with TTX failed to affect the expression of rho2 subunits. Electrophysiological recordings revealed the presence of spontaneous Ca(2+) currents in SC cultures and preventing these, by treatment with blockers of L-type Ca(2+) channels, caused rho2 mRNA expression to decline to in vivo levels. In contrast, rho1 subunit mRNA levels remained unchanged, indicating that the two subunits are independently regulated. Surprisingly, both tonic activation and blockade of GABA(C) receptors upregulated rho1/rho2 mRNA expression. Further, NGF and BDNF promoted such expression during an early postnatal time window. In vivo, expression of the rho2 mRNA in the SC, and the rho2/rho3 mRNA in the retina increased with age. Expression of the rho2 mRNA in the visual cortex, and the rho1 mRNA in the retina and SC was constant. Subunit mRNA expression was similar in dark-reared animals, indicating that visual experience has no influence. These experiments suggest that GABA(C) receptor expression in the SC is regulated during postnatal development. While visual experience seems to have no influence on GABA(C) receptor subunits, spontaneous calcium currents selectively promote rho2 expression and both rho1 and rho2 are autoregulated both by GABA(C) receptor activity and by neurotrophic factors.
Jost
Britta
B
AG Entwicklungsneurobiologie, Fakultät für Biologie, Ruhr-Universität Bochum, Bochum, Germany.
Grabert
Jochen
J
Patz
Silke
S
Schmidt
Matthias
M
Wahle
Petra
P
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D018079:Receptors, GABA / Q000235:genetics* / Q000378:metabolism; D013477:Superior Colliculi / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D014795:Visual Pathways / Q000254:growth & development; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C087200:GABA-C receptor; D009414:Nerve Growth Factors; D021122:Protein Subunits; D012333:RNA, Messenger; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D020932:Nerve Growth Factor