Dopamine facilitates the response to glutamatergic inputs in astrocyte cell models

Autor(es)

Bezerra, Thiago Ohno ; Roque, Antonio C.

• Tipo de documento: Artigo Científico
• Fonte: PLOS COMPUTATIONAL BIOLOGY; v. 20, n. 12, p. 26-pg., 2024-12-01.

Resumo

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)

• Processo FAPESP: 13/07699-0 - Centro de Pesquisa, Inovação e Difusão em Neuromatemática - NeuroMat
• Beneficiário: Oswaldo Baffa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 21/12832-7 - Impacto da Transmissão Dopaminérgica em uma Rede Neural Acompanhada por Astrócitos para a Simulação da Memória de Trabalho
• Beneficiário: Thiago Takechi Ohno Bezerra
• Modalidade de apoio: Bolsas no Brasil - Doutorado