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In brain neurons, dopamine D<jats:sub>1<\/jats:sub>receptors (D<jats:sub>1<\/jats:sub>Rs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between D<jats:sub>1<\/jats:sub>Rs, Src and NMDARs in retinal neurons. We reveal that dopamine-mediated D<jats:sub>1<\/jats:sub>R stimulation provoked NMDAR hypofunction in retinal neurons by attenuating NMDA-gated currents, by preventing NMDA-elicited calcium mobilization and by decreasing the phosphorylation of NMDAR subunit GluN2B. This dopamine effect was dependent on upregulation of the canonical D<jats:sub>1<\/jats:sub>R\/adenylyl cyclase\/cAMP\/PKA pathway, of PKA-induced activation of C-terminal Src kinase (Csk) and of Src inhibition. Accordingly, knocking down Csk or overexpressing a Csk phosphoresistant Src mutant abrogated the dopamine-induced NMDAR hypofunction. Overall, the interplay between dopamine and NMDAR hypofunction, through the D<jats:sub>1<\/jats:sub>R\/Csk\/Src\/GluN2B pathway, might impact on light-regulated synaptic activity in retinal neurons.<\/jats:p>","DOI":"10.1038\/srep40912","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T11:55:47Z","timestamp":1484740547000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Dopamine promotes NMDA receptor hypofunction in the retina through D1 receptor-mediated Csk activation, Src inhibition and decrease of GluN2B phosphorylation"],"prefix":"10.1038","volume":"7","author":[{"given":"Renato","family":"Socodato","sequence":"first","affiliation":[]},{"given":"Felipe N.","family":"Santiago","sequence":"additional","affiliation":[]},{"given":"Camila C.","family":"Portugal","sequence":"additional","affiliation":[]},{"given":"Ivan","family":"Domith","sequence":"additional","affiliation":[]},{"given":"Tha\u00edsa G.","family":"Encarna\u00e7\u00e3o","sequence":"additional","affiliation":[]},{"given":"Erick C.","family":"Loiola","sequence":"additional","affiliation":[]},{"given":"Ana L. M.","family":"Ventura","sequence":"additional","affiliation":[]},{"given":"Marcelo","family":"Cossenza","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o B.","family":"Relvas","sequence":"additional","affiliation":[]},{"given":"Newton G.","family":"Castro","sequence":"additional","affiliation":[]},{"given":"Roberto","family":"Paes-de-Carvalho","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2017,1,18]]},"reference":[{"key":"BFsrep40912_CR1","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/j.1600-0773.1963.tb01730.x","volume":"20","author":"A Carlsson","year":"1963","unstructured":"Carlsson, A. & Lindqvist, M. Effect of Chlorpromazine or Haloperidol on Formation of 3\u2010Methoxytyramine and Normetanephrine in Mouse Brain. 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