title: A model of dopamine modulated glutamatergic synapse.
abstract: The dopamine neurotransmitter regulates important neural pathways and its action in the brain is very complex. When dopaminergic neurons make synapses on spiny neurons of the striatum nucleus, they tune the responsiveness of glutamatergic synapses by means of the dopamine D1 and D2 receptors. We studied the effect of dopamine D1 receptors on glutamatergic synapse of GABAergic spiny neurons in striatum nucleus where they are located on the neck of the same spine. The action of dopamine consists essentially in promoting the phosphorylation of AMPA and NMDA receptors thus increasing the Excitatory Post Synaptic Current peak amplitude. The consequence is a cooperative effect of glutamatergic and dopaminergic synapses for the regulation of the GABAergic neuronal code. The mechanisms by which the phosphorylation induces the increase of the EPSC amplitude still remain unclear although the lack of this regulation can be involved in several pathologies as, for example, the Parkinson's disease. We tested, by computational experiments based on our model of glutamatergic synapse, three parameters of the synaptic function that could be involved in dopamine action: (a) time binding of glutamate to receptors; (b) open probability of the receptors; and (c) single receptor conductance. For different reasons, any of the three parameters could be responsible of the increased EPSC-dopamine-dependent. Our computational results were compared and discussed with experimental results found in literature. Although for our model both the open probability and the single receptor conductance can reproduce the phosphorylation effect of dopamine, we argue that the dopamine effect consists essentially in an increase of the single receptor conductance due to a 3D rearrangement of the phosphorylated receptors.
authors.affiliation: Istituto di Cibernetica "E. Caianiello" del CNR, Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy. Electronic address: vito.dimaio@cnr.it.
authors.forename: Vito
authors.initials: V
authors.lastname: Di Maio
authors.affiliation: Istituto di Cibernetica "E. Caianiello" del CNR, Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ventriglia
authors.affiliation: Istituto di Cibernetica "E. Caianiello" del CNR, Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Santillo
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008959:Models, Neurological; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004298:Dopamine
keywords: Dopamine; Glutamatergic synapses; Synaptic modelling