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Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
Glucagon-like peptide-1 (GLP-1) is mainly secreted by preproglucagon neurons; it plays important roles in modulating neuronal activity and synaptic transmission through its receptors. In the present study, we investigated the effects of GLP-1 on parallel fiber–Purkinje cell (PF-PC) synaptic transmis...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188593/ https://www.ncbi.nlm.nih.gov/pubmed/37193712 http://dx.doi.org/10.1038/s41598-023-34070-6 |
Sumario: | Glucagon-like peptide-1 (GLP-1) is mainly secreted by preproglucagon neurons; it plays important roles in modulating neuronal activity and synaptic transmission through its receptors. In the present study, we investigated the effects of GLP-1 on parallel fiber–Purkinje cell (PF-PC) synaptic transmission in mouse cerebellar slices using whole-cell patch-clamp recording and pharmacology methods. In the presence of a γ-aminobutyric acid type A receptor antagonist, bath application of GLP-1 (100 nM) enhanced PF-PC synaptic transmission, with an increased amplitude of evoked excitatory postsynaptic synaptic currents (EPSCs) and a decreased paired-pulse ratio. The GLP-1-induced enhancement of evoked EPSCs was abolished by a selective GLP-1 receptor antagonist, exendin 9–39, as well as by the extracellular application of a specific protein kinase A (PKA) inhibitor, KT5720. In contrast, inhibiting postsynaptic PKA with a protein kinase inhibitor peptide-containing internal solution failed to block the GLP-1-induced enhancement of evoked EPSCs. In the presence of a mixture of gabazine (20 μM) and tetrodotoxin (1 μM), application GLP-1 significantly increased frequency, but not amplitude of miniature EPSCs via PKA signaling pathway. The GLP-1-induced increase in miniature EPSC frequency was blocked by both exendin 9–39 and KT5720. Together, our results indicate that GLP-1 receptor activation enhances glutamate release at PF-PC synapses via the PKA signaling pathway, resulting in enhanced PF-PC synaptic transmission in mice in vitro. These findings suggest that, in living animals, GLP-1 has a critical role in the modulation of cerebellar function by regulating excitatory synaptic transmission at PF-PC synapses. |
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