title: Combination of group I mGlu receptors antagonist with dopaminergic agonists strengthens the synaptic transmission at corticostriatal synapses in culture.
abstract: Restoring synaptic plasticity in neurodegenerative diseases could prevent neuronal degeneration, as well as motor and cognitive disorders. In Parkinson's disease, synaptic plasticity at corticostriatal synapses is altered. Dendrites of striatal medium spiny neurons (MSNs) receive dopaminergic inputs from the substantia nigra and glutamatergic cortical afferents. Because both glutamate and dopamine are required to induce and sustain MSNs plasticity, the particular molecular mechanisms involved at this synaptic triad are difficult to understand. In the present work, we established a convenient in vitro model of the corticostriatal synapse to study synaptic plasticity. We focused on long-term depression involving group I metabotropic glutamate (mGlu) receptors. We found that in striatal neurons co-cultured with cortical neurons, the absence of dopaminergic stimuli favored the excess of glutamatergic drive from cortical neuron terminals, thus resulting in a constitutive depression of the corticostriatal glutamatergic transmission. Indeed, concomitant blockade of group I mGlu receptors and activation of dopaminergic receptors stably reduced the depression of the synaptic transmission. Thus the dependence on glutamate and dopamine balance of the corticostriatal synapse responsiveness validates the accuracy of this manageable in vitro model to depict the molecular pathways involved in the plasticity at corticostriatal synapses and to test restorative therapeutic approaches in Parkinson's disease. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, F-34000 Montpellier, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Burguière
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Valjent
authors.forename: Jonathan
authors.initials: J
authors.lastname: Roger
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Laurent
authors.initials: L
authors.lastname: Fagni
authors.forename: Julie
authors.initials: J
authors.lastname: Perroy
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D049229:Dendritic Spines / Q000648:ultrastructure; D018491:Dopamine Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D061251:Primary Cell Culture / Q000379:methods; D011954:Receptors, Dopamine / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D011954:Receptors, Dopamine; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid