Title: Calcium-independent astrocytic lipid release modulates neuronal excitability

Accumulating data point to a key role of Ca²⁺-dependent gliotransmitter release as a modulator of neuronal networks. Here, we tested the hypothesis that astrocytes also release lipid modulators through activation of Ca²⁺-independent phospholipase A2 (iPLA₂) activity in response to agonist exposure. We found that cultured rat astrocytes treated with selective ATP and glutamatergic agonists released arachidonic acid (AA) and/or its derivatives, including the endogenous cannabinoid 2-arachidonoyl-sn-glycerol (2AG) and prostaglandin E2 (PGE₂). Surprisingly, buffering of cytosolic Ca²⁺ resulted in a sharp increase in agonist-induced astrocytic lipid release. In addition, astrocytic release of PGE₂ enhanced miniature excitatory post-synaptic potentials (mEPSPs) by inhibiting the opening of neuronal Kv channels in brain slices. This study provides the first evidence for the existence of a Ca²⁺-independent pathway regulating the release of PGE₂ from astrocytes and furthermore demonstrates a functional role for astrocytic lipid release in the modulation of synaptic activity.

Dr. Smith is a principal investigator in the Neuroscience Research Center at Children's National Hospital.

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