BC1 regulation of metabotropic glutamate receptor-mediated neuronal excitability.
Regulatory RNAs have been suggested to contribute to the control of gene expression in eukaryotes. Brain cytoplasmic (BC) RNAs are regulatory RNAs that control translation initiation. We now report that neuronal BC1 RNA plays an instrumental role in the protein-synthesis-dependent implementation of neuronal excitation-repression equilibria. BC1 repression counter-regulates translational stimulation resulting from synaptic activation of group I metabotropic glutamate receptors (mGluRs). Absence of BC1 RNA precipitates plasticity dysregulation in the form of neuronal hyperexcitability, elicited by group I mGluR-stimulated translation and signaled through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. Dysregulation of group I mGluR function in the absence of BC1 RNA gives rise to abnormal brain function. Cortical EEG recordings from freely moving BC1(-/-) animals show that group I mGluR-mediated oscillations in the gamma frequency range are significantly elevated. When subjected to sensory stimulation, these animals display an acute group I mGluR-dependent propensity for convulsive seizures. Inadequate RNA control in neurons is thus causally linked to heightened group I mGluR-stimulated translation, neuronal hyperexcitability, heightened gamma band oscillations, and epileptogenesis. These data highlight the significance of small RNA control in neuronal plasticity.
Zhong
Jun
J
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York, Brooklyn, 11203, USA. jzhong@downstate.edu
Chuang
Shih-Chieh
SC
Bianchi
Riccardo
R
Zhao
Wangfa
W
Lee
Heekyung
H
Fenton
André A
AA
Wong
Robert K S
RK
Tiedge
Henri
H
D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D004569:Electroencephalography; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000096:biosynthesis; D051528:Guanylate Kinases; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010507:Periodicity; D020733:RNA, Small Cytoplasmic / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
D000076122:Disks Large Homolog 4 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020733:RNA, Small Cytoplasmic; D018094:Receptors, Metabotropic Glutamate; C117734:BC1 RNA; C501447:Dlg4 protein, mouse; C497684:Fmr1 protein, mouse
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