The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum

Diego Centonze, Silvia Rossi, Ilaria Napoli, Valentina Mercaldo, Caroline Lacoux, Francesca Ferrari, Maria Teresa Ciotti, Valentina De Chiara, Chiara Prosperetti, Mauro Maccarrone, Filomena Fezza, Paolo Calabresi, Giorgio Bernardi, Claudia Bagni

Research output: Contribution to journalArticlepeer-review

Abstract

Dopamine D2 receptor (D2DR)-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 D2 receptors in this brain area are essentially obscure. Wehave studied the physiological responses of the D2DR 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 D2-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D2 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 CB1 receptors was intact in the striatum of BC1 knock-out (KO) mice despite D2 and CB1 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 D2-mediated transmission. Because D2DR 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 D2DR indirectly, probably regulating translation of molecules involved in D2DR turnover and/or stability.

Original languageEnglish
Pages (from-to)8885-8892
Number of pages8
JournalJournal of Neuroscience
Volume27
Issue number33
DOIs
Publication statusPublished - Jan 15 2007

Keywords

  • Electrophysiology
  • GABA transmission
  • IPSC
  • mRNA localization
  • Noncoding RNA
  • Plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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