Distinct patterns of expression and regulation of GABA receptors containing the delta subunit in cerebellar granule and hippocampal neurons.
Neuronal plasticity is achieved by regulation of the expression of genes for neurotransmitter receptors such as the type A receptor (GABA(A)R) for gamma-aminobutyric acid. We now show that two different rat neuronal populations in culture manifest distinct patterns of GABA(A)R plasticity in response to identical stimuli. Whereas prolonged exposure to ethanol had no effect on expression of the delta subunit of GABA(A)Rs at the mRNA or protein level in cerebellar granule neurons, it increased the abundance of delta subunit mRNA and protein in hippocampal neurons. Subsequent ethanol withdrawal transiently down-regulated delta subunit expression in cerebellar granule neurons and gradually normalized that in hippocampal neurons. These effects of ethanol exposure and withdrawal were accompanied by corresponding functional changes in GABA(A)Rs. GABA(A)Rs containing the delta subunit were also distributed differentially in the cerebellar and hippocampal neurons. These findings reveal complex and distinct mechanisms of regulation of the expression of GABA(A)Rs that contain the delta subunit in different neuronal types.
Follesa
Paolo
P
Department of Experimental Biology, Section of Neuroscience, University of Cagliari, Cagliari, Italy. follesa@unica.it
Mostallino
Maria Cristina
MC
Biggio
Francesca
F
Gorini
Giorgio
G
Caria
Stefania
S
Busonero
Fabio
F
Murru
Luca
L
Mura
Maria Luisa
ML
Sanna
Enrico
E
Biggio
Giovanni
G
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002531:Cerebellum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D000431:Ethanol / Q000008:administration & dosage; D018755:GABA Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D007555:Isoxazoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011280:Pregnanolone / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D000777:Anesthetics; D002492:Central Nervous System Depressants; D018755:GABA Agonists; D007555:Isoxazoles; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D000431:Ethanol; D011280:Pregnanolone; C015542:gaboxadol