ENDOCANNABINOIDS MEDIATE NEURON-ASTROCYTE SIGNALING AND STIMULATE GLUTAMATE RELEASE FROM ASTROCYTES
Abstract number: P22
The astrocyte Ca2+ is crucial in the astrocyte-neuron comunication. Cannabinoid receptors (CBR) play key roles in brain physiology but their expression and function in astrocytes remain unknown. We investigated the expression of cannnabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication. We used electrophysiological and Ca2+ imaging techniques in mice brain slices.
We found:
1) Local application of CBR agonists increased the astrocyte Ca2+ levels. The Ca2+ elevations were insensitive to glutamatergic, GABAergic, cholinergic, and purinergic antagonist receptors but were abolished by the CB1 receptor antagonist AM251. Furthermore, Ca2+ elevations were not observed in slices from CB1R-/- transgenic mice. Therefore, the observed responses were mediated by CB1R activation in astrocytes.
2) Cannabinoid-induced astrocyte Ca2+ elevations were unaffected by pertussis toxin but were abolished by PLC inhibitors and thapsigargin.
3) Endocannabinoids released by depolarization of pyramidal neurons modulated Ca2+ signal. These effects were abolished by AM251.
4) Endocannabinoid-mediated astrocyte Ca2+ elevations stimulate the release of glutamate from astrocytes, evoking NMDA receptor-dependent slow inward currents (SICs) in adjacent neurons.
We conclude:
1. Hippocampal astrocytes in situ express functional CB1Rs.
2. CB1 receptors in astrocytes are activated by endocannabinoids released from pyramidal neurons, increasing the Ca2+ levels in astrocytes.
3. Present results show a new form of neuron-astrocyte communication based on endocannabinoid signalling, and suggest a new endocannabinoid-glutamate signalling pathway, where astrocytes serve as a bridge for interneuronal communication.
Supported by: Ministerio de Educación y Ciencia (BFU2004-00448) and CAM (200620M083), Spain. MN is a FPI-MEC predoctoral fellow.