Tesis doctoral de Marta Navarrete Llinás
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.
Datos académicos de la tesis doctoral «Comunicación entre neuronas y astrocitos mediada por endocannabinoides«
- Título de la tesis: Comunicación entre neuronas y astrocitos mediada por endocannabinoides
- Autor: Marta Navarrete Llinás
- Universidad: Autónoma de Madrid
- Fecha de lectura de la tesis: 22/05/2009
Dirección y tribunal
- Director de la tesis
- Alfonso Araque Almendros
- Tribunal
- Presidente del tribunal: Carlos Avendaño trueba
- Alberto e Pereda (vocal)
- pablo e Castillo (vocal)
- eduardo Martín montiel (vocal)