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The Journal of Neuroscience, August 15, 2007, 27(33):8885-8892; doi:10.1523/JNEUROSCI.0548-07.2007

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Cellular/Molecular
The Brain Cytoplasmic RNA BC1 Regulates Dopamine D₂ Receptor-Mediated Transmission in the Striatum

Diego Centonze,^1,4 * Silvia Rossi,^1,4 * Ilaria Napoli,^2,4 Valentina Mercaldo,^2,4 Caroline Lacoux,^2,4 Francesca Ferrari,^2,4 Maria Teresa Ciotti,^2,5 Valentina De Chiara,^1,4 Chiara Prosperetti,^1,4 Mauro Maccarrone,^4,6 Filomena Fezza,^3,4 Paolo Calabresi,^4,7 Giorgio Bernardi,^1,4 and Claudia Bagni^2,4

¹Clinica Neurologica, Dipartimento di Neuroscienze, ²Dipartimento di Biologia, and ³Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università Tor Vergata, 00133 Rome, Italy, ⁴Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy, ⁵Consiglio Nazionale delle Ricerche/CERC, 00143 Rome, Italy, ⁶Dipartimento di Scienze Biomediche Comparate, Università degli Studi di Teramo, 64100 Teramo, Italy, and ⁷Clinica Neurologica, Università di Perugia, Ospedale Silvestrini, 06156 Perugia, Italy

Correspondence should be addressed to either of the following: Claudia Bagni, Dipartimento di Biologia, Università Tor Vergata, 00133 Rome, Italy, Email: claudia.bagni{at}uniroma2.it; or Diego Centonze, Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, 00133 Rome, Italy, Email: centonze{at}uniroma2.it

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. 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 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.

Key words: electrophysiology; plasticity; IPSC; GABA transmission; noncoding RNA; mRNA localization

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Received Feb. 7, 2007; revised June 7, 2007; accepted June 22, 2007.

Correspondence should be addressed to either of the following: Claudia Bagni, Dipartimento di Biologia, Università Tor Vergata, 00133 Rome, Italy, Email: claudia.bagni{at}uniroma2.it; or Diego Centonze, Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, 00133 Rome, Italy, Email: centonze{at}uniroma2.it

This article has been cited by other articles:

				T. R. Mercer, M. E. Dinger, J. Mariani, K. S. Kosik, M. F. Mehler, and J. S. Mattick Noncoding RNAs in Long-Term Memory Formation Neuroscientist, October 1, 2008; 14(5): 434 - 445. [Abstract] [PDF]

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