Article: article from journal or magazin.
The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.
Animals, Animals, Newborn, Biphenyl Compounds/pharmacology, Cells, Cultured, Corpus Striatum/cytology, Dopamine D2 Receptor Antagonists, Glutamate Decarboxylase/metabolism, Guanosine 5'-O-(3-Thiotriphosphate)/pharmacokinetics, In Vitro Techniques, Inhibitory Postsynaptic Potentials/drug effects, Inhibitory Postsynaptic Potentials/physiology, Isoenzymes/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microtubule-Associated Proteins/metabolism, Neurons/drug effects, Neurons/physiology, Oligonucleotides/pharmacology, Patch-Clamp Techniques/methods, Piperazines/pharmacology, RNA, Long Noncoding, RNA, Messenger/biosynthesis, RNA, Untranslated, Receptors, Dopamine D2/agonists, Receptors, Dopamine D2/chemistry, Receptors, Dopamine D2/physiology, Reverse Transcriptase Polymerase Chain Reaction/methods, Ribonucleoproteins, Small Cytoplasmic/deficiency, Ribonucleoproteins, Small Cytoplasmic/physiology, Synaptic Transmission/drug effects, Synaptic Transmission/physiology, gamma-Aminobutyric Acid/metabolism
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