DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2018-11-07 - Colloque/Abstract - Anglais - page(s)

Massie ann, Bentea Eduard, Villers Agnès , Moore Cynthia, Funk A, O'Donovan S M, Verbruggen Lise, Depasquale E, Churchill M J, Sato H, Ris Laurence , Meshul C K, McCullumsmith R E, "The cystine/glutamate antiporter system xc- as modulator of corticostriatal neurotransmission" in Neuroscience 2018, 651.06. 2018, San Diego, USA, 2018

  • Codes CREF : Neurophysiologie (DI3224)
  • Unités de recherche UMONS : Neurosciences (M119)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de recherche interdisciplinaire en Psychophysiologie et Electrophysiologie de la cognition (CIPsE)

Abstract(s) :

(Anglais) The cystine/glutamate antiporter system xc-, with xCT as specific subunit, is mainly located on glial cells and couples the import of cystine with the export of glutamate. As such, system xc- contributes substantially to ambient extracellular glutamate levels in various regions of the brain, including the striatum and hippocampus. However, the physiological function of system xc- in the central nervous system remains poorly understood, despite its high expression in the brain. As a source of glial extrasynaptic glutamate, system xc- can affect synaptic neurotransmission as a mechanism of neuro-glial communication. In the current study, we investigated how system xc- regulates transmission at corticostriatal synapses, one of the two major types of striatal excitatory synapses. Electrophysiological recordings identified a significant decrease in the amplitude of striatal field excitatory postsynaptic potentials in mice genetically lacking xCT (xCT-/- mice) following stimulation of corticostriatal fibers. Further, using electron microscopy, we observed depletion of glutamate immunogold labeling from corticostriatal terminals and their corresponding dendritic spines in xCT-/- mice. Genetic deletion of xCT did not, however, affect the morphology of corticostriatal synapses, the density of cortical innervation or spine density. Proteomic analysis of the striatum of xCT-/- mice revealed decreased expression of a wide range of proteins involved in regulating presynaptic neurotransmitter release, including synaptophysin, VGLUT1, and members of the synapsin, septin, and syntaxin families. In addition, kinome profiling identified changes in striatal serine/threonine kinase activity, highlighting ERK signaling as a possible node of kinase dysregulation in xCT-/- mice. Finally, in the marble burying test, a paradigm sensitive to changes in corticostriatal function, we measured a significant increase in repetitive digging behavior in xCT-/- mice. Together, our findings shed new light on the role of system xc- in controlling synaptic transmission. We hypothesize that the corticostriatal circuit deficits present in xCT-/- mice are a consequence of depletion of presynaptic glutamate stores, deficits in the presynaptic glutamate release machinery and/or aberrant ERK signaling, avenues we are currently exploring. As a novel modulator of corticostriatal transmission, system xc- may be relevant to neuropsychiatric disorders characterized by corticostriatal dysfunction and repetitive behavior, such as obsessive-compulsive behavior and autism.