A model of dopamine modulated glutamatergic synapse. (October 2015)

• Record Type: Journal Article
• Authors: Di Maio, Vito; Ventriglia, Francesco; Santillo, Silvia
• Is Part Of: Bio systems. Volume 136(2015:Oct.)
• Page Start: 59
• Page End: 65
• Publication Date: 2015-10
• Subjects: Synaptic modelling -- Glutamatergic synapses -- Dopamine; Biological systems -- Periodicals; Biology -- Periodicals; Biology -- Periodicals; Evolution -- Periodicals; Biologie -- Périodiques; Évolution -- Périodiques; 570
• DOI: 10.1016/j.biosystems.2015.05.001
• Languages: English
• ISSNs: 0303-2647

Abstract

Abstract : Graphical abstract: Abstract : Highlights: The cooperative effect of AMPA and NMDA receptors activity in a glutamatergic synapse is considered. The effect of phosphorylation dopamine-dependent on these receptors is investigated. Results shown that the increase of single receptor conductance is the most probable effect of phosphorylation. 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.