Astrocytes are recognized as active and indispensable regulators of brain function. Increasing evidence indicates that modulating astrocytic activity in different brain regions can significantly impact neuronal communication and behavioral outcomes. Notably, many of the processes through which astrocytes influence neuronal activity are driven by calcium signaling within astrocytic compartments, which induces gliotransmitter release. Interestingly, the discovery of new gliotransmitters, along with astrocyte populations specialized in the release of each specific gliotransmitter, is advancing rapidly, opening new ways by which specific astrocyte populations could regulate specific neural circuits.

In this work, we propose that astrocytes are able to produce and release a lipid messenger, the endocannabinoid (eCB) 2-AG, through an intracellular calcium-dependent mechanism. This astrocyte-derived eCB relies on the expression of diacylglycerol lipase A (DAGLA), which appears to be restricted to a specific subpopulation of astrocytes throughout the brain. Interestingly, removing DAGLA from astrocytes in different brain regions modulates neuronal excitability and behavioral outcomes, highlighting the role of this signaling pathway in the control of brain functions by astrocytes. 

These results reveal a new mechanism of astrocyte-neuron communication and a new pathway through which calcium signaling in astrocytes can regulate brain function.

More information:

• Abel Eraso – Bordeaux Neurocampus