The brain cytoplasmic RNA BC1 regulates dopamine D-2 receptor-mediated transmission in the striatum
Centonze, Diego × Rossi, Silvia Napoli, Ilaria Mercaldo, Valentina Lacoux, Caroline Ferrari, Francesca Ciotti, Maria Teresa De Chiara, Valentina Prosperetti, Chiara Maccarrone, Mauro Fezza, Filomena Calabresi, Paolo Bernardi, Giorgio Bagni, Claudia #
Journal of neuroscience vol:27 issue:33 pages:8885-8892
Dopamine D-2 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 D-2 receptors in this brain area are essentially obscure. We have 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 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 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.