Dopamine facilitates the response to glutamatergic inputs in astrocyte cell models

Author(s)

Bezerra, Thiago Ohno ; Roque, Antonio C.

• Document type: Journal article
• Source: PLOS COMPUTATIONAL BIOLOGY; v. 20, n. 12, p. 26-pg., 2024-12-01.

Abstract

Astrocytes respond to neurotransmitters by increasing their intracellular Ca2+ concentration (Ca2+ signals). While glutamate released by neurons trigger Ca2+ signals through IP3- and glutamate transporter-dependent mechanisms, dopamine released in distant sites activates astrocytes via dopaminergic receptors. However, little is known about the modulatory effects of dopamine on glutamate-evoked astrocytic activity. To investigate this question, we developed multi-compartment, conductance-based astrocyte models with three distinct morphologies: unipolar; bipolar; and bifurcated-terminal. Glutamate induced localized responses, while dopamine activated all compartments. In the unipolar model, global dopaminergic stimulation reduced the threshold frequency of glutamatergic stimulation required to activate Ca2+ signals. Phase-plane analysis of a simplified version of this model revealed that Ca2+ signals are influenced by compartment radius and neurotransmitter type. Morphology significantly influenced glutamate-dopamine interactions. In the bipolar model, glutamatergic stimulation in one process minimally affected the other. Conversely, in the bifurcated-terminal model, where a single process bifurcates into two secondary processes, high-frequency glutamatergic stimulation in one secondary process evoked Ca2+ signals in the other. Dopamine further facilitated this latter cross-process interaction by lowering the glutamatergic stimulation frequency needed to elicit Ca2+ signals in the adjacent secondary process. These findings suggest that dopamine enhances the initiation and propagation of glutamate-evoked Ca2+ signals, with the extent of propagation depending on astrocytic morphology and the spatial distribution of glutamatergic inputs. (AU)

• FAPESP's process: 13/07699-0 - Research, Innovation and Dissemination Center for Neuromathematics - NeuroMat
• Grantee: Oswaldo Baffa Filho
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 21/12832-7 - Impact of Dopaminergic Transmission over a Neural Network Accompanied by Astrocytes for the Simulation of Working Memory
• Grantee: Thiago Takechi Ohno Bezerra
• Support Opportunities: Scholarships in Brazil - Doctorate