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Glial ATP and Large Pore Channels Modulate Synaptic Strength in Response to Chronic Inactivity.
Rafael, Alberto; Cairus, Andrea; Tizzoni, Marina; Abudara, Verónica; Vitureira, Nathalia.
Afiliação
  • Rafael A; Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Cairus A; Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Tizzoni M; Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Abudara V; Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Vitureira N; Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. nvitureira@fmed.edu.uy.
Mol Neurobiol ; 57(6): 2856-2869, 2020 Jun.
Article em En | MEDLINE | ID: mdl-32388797
A key feature of neurotransmission is its ability to adapt to changes in neuronal environment, which is essential for many brain functions. Homeostatic synaptic plasticity (HSP) emerges as a compensatory mechanism used by neurons to adjust their excitability in response to changes in synaptic activity. Recently, glial cells emerged as modulators for neurotransmission by releasing gliotransmitters into the synaptic cleft through pathways that include P2X7 receptors (P2X7R), connexons, and pannexons. However, the role of gliotransmission in the activity-dependent adjustment of presynaptic strength is still an open question. Here, we investigated whether glial cells participate in HSP upon chronic inactivity and the role of adenosine triphosphate (ATP), connexin43 hemichannels (Cx43HCs), and pannexin1 (Panx1) channels in this process. We used immunocytochemistry against vesicular glutamate transporter 1 (vGlut1) to estimate changes in synaptic strength in hippocampal dissociated cultures. Pharmacological manipulations indicate that glial-derived ATP and P2X7R are required for HSP. In addition, inhibition of Cx43 and Panx1 channels reveals a pivotal role for these channels in the compensatory adjustment of synaptic strength, emerging as new pathways for ATP release upon inactivity. The involvement of Panx1 channels was confirmed by using Panx1-deficient animals. Lacking Panx1 in neurons is sufficient to prevent the P2X7R-dependent upregulation of presynaptic strength; however, the P2X7R-dependent compensatory adjustment of synapse density requires both neuronal and glial Panx1. Together, our data supports an essential role for glial ATP signaling and Cx43HCs and Panx1 channels in the homeostatic adjustment of synaptic strength in hippocampal cultures upon chronic inactivity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Trifosfato de Adenosina / Neuroglia / Conexinas / Transmissão Sináptica / Proteínas do Tecido Nervoso / Neurônios Limite: Animals Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Trifosfato de Adenosina / Neuroglia / Conexinas / Transmissão Sináptica / Proteínas do Tecido Nervoso / Neurônios Limite: Animals Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Estados Unidos