Comunicación entre neuronas y astrocitos mediada por endocannabinoides

• Autores: Marta Navarrete
• Directores de la Tesis: Alfonso Araque Almendros (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2009
• Idioma: español
• Tribunal Calificador de la Tesis: Carlos Avendaño Trueba (presid.), Washington Buño Buceta (secret.), Pablo Castillo (voc.), Eduardo Martín Montiel (voc.), Alberto E Pereda (voc.)
• Materias:
  • Ciencias de la vida
    • Fisiología humana
      • Fisiología del sistema nervioso central
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • Endocannabinoids and their receptor CB1 play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behaviour are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. Using electrophysiological and Ca2+ imaging techniques in mouse we show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospolipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. Moreover, endocannabinoids released by hippocampal pyramidal neurons increase the probability of transmitter release at single CA3-CA1 synapses. This synaptic potentiation is due to CB1R-induced Ca2+ elevations in astrocytes, which stimulate the release of glutamate that activates presynaptic group I metabotropic glutamate receptors. While endocannabinoids induce Gi/o protein-mediated homosynaptic depression by activation of presynaptic CB1Rs, they lead to heterosynaptic potentiation by activation of CB1Rs in astrocytes. These results reveal the existence of a new endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for non-synaptic interneuronal communication. In summary, astrocytes respond to endocannabinoids, which leads to the modulation of neuronal excitability and synaptic transmission, indicating that astrocytes are actively involved in brain physiology.