RT Journal Article
T1 Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
A1 Ramírez Franco, José Jorge
A1 Bartolomé-Martín, David
A1 Alonso, Beatris
A1 Torres Molina, Magdalena Isabel
A1 Sánchez-Prieto Borja, José
AB Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1α protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals.
PB PLOS
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/129943
UL https://hdl.handle.net/20.500.14352/129943
LA eng
NO Ramírez-Franco J, Bartolomé-Martín D, Alonso B, Torres M, Sánchez-Prieto J. Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells. PLoS One. 2014 Feb 12;9(2):e88594.
NO Justificación de autores:Conceived and designed the experiments: JRF MT JSP. Performed the experiments: JRF DBM BA. Analyzed the data: JRF DBM BA. Contributed reagents/materials/analysis tools: DBM. Wrote the paper: MT JSP.Becas:CAM-I2M2 2011-BMD-2349 (José Sánchez Prieto y Magdalena Torres)
NO Ministerio de Economía y Comercio (España)
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
DS Docta Complutense
RD 13 ene 2026