title: Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons.
abstract: Neuregulin 1 (NRG1) is a trophic factor that has an essential role in the nervous system by modulating neurodevelopment, neurotransmission and synaptic plasticity. Despite the evidence that NRG1 and its receptors, ErbB tyrosine kinases, are expressed in mesencephalic dopaminergic nuclei and their functional alterations are reported in schizophrenia and Parkinson's disease, the role of NRG1/ErbB signalling in dopaminergic neurons remains unclear. Here we found that NRG1 selectively increases the metabotropic glutamate receptor 1 (mGluR1)-activated currents by inducing synthesis and trafficking to membrane of functional receptors and stimulates phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway, which is required for mGluR1 function. Notably, an endogenous NRG1/ErbB tone is necessary to maintain mGluR1 function, by preserving its surface membrane expression in dopaminergic neurons. Consequently, it enables striatal mGluR1-induced dopamine outflow in in vivo conditions. Our results identify a novel role of NRG1 in the dopaminergic neurons, whose functional alteration might contribute to devastating diseases, such as schizophrenia and Parkinson's disease.
authors.affiliation: 1] Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy [2] Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ledonne
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Nobili
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: E C
authors.initials: EC
authors.lastname: Latagliata
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cavallucci
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Guatteo
authors.affiliation: 1] Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy [2] Department of Psychology and 'Daniel Bovet' Center, University of Rome 'La Sapienza', Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Puglisi-Allegra
authors.affiliation: 1] Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy [2] Laboratory of Molecular Neurosciences, Medical School University Campus-Biomedico, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amelio
authors.affiliation: 1] Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy [2] Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: N B
authors.initials: NB
authors.lastname: Mercuri
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology*; D017551:Microdialysis; D020890:Neuregulin-1 / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D004298:Dopamine; D066246:ErbB Receptors; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018094:Receptors, Metabotropic Glutamate; D058570:TOR Serine-Threonine Kinases; C490580:Nrg1 protein, rat; C104077:metabotropic glutamate receptor type 1; C546845:mTOR protein, rat