Increase in arachidonic acid concentration in a postsynaptic membrane fraction following the induction of long-term potentiation in the dentate gyrus.
We have determined the concentration of free fatty acids in membranes of slices prepared from the dentate gyrus following the induction of long-term potentiation in the anaesthetized rat. Compared to unpotentiated tissue, there was a significant increase in the concentration of free arachidonic acid 2.5 min, 45 min and 3 h after induction of long-term potentiation. There was no corresponding increase in oleic, stearic or palmitic acids. To account for the increase in free arachidonate, the activities of phospholipase A2, phospholipase A1 and phospholipase C were determined at the same three time intervals in control and potentiated tissue. Two-and-a-half minutes after the induction of long-term potentiation, activity of phospholipase A2 was enhanced, while at 45 min, and at 3 h phospholipase C activity was increased. These results suggest that the liberation of free arachidonate is due initially to phospholipase A2 activity, but that at later stages of long-term potentiation, control switches to phospholipase C. Subcellular fractionation experiments revealed an increase in free arachidonate in the postsynaptic density fraction 45 min after induction of long-term potentiation, without significant changes in synaptosomal- or glial-enriched fractions. These results are consistent with the hypothesis that arachidonic acid, released from a postsynaptic site, acts as a trophic retrograde synaptic signal in long-term potentiation in the dentate gyrus.
Clements
M P
MP
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, Mill Hill, London, U.K.
Bliss
T V
TV
Lynch
M A
MA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D004558:Electric Stimulation; D006624:Hippocampus / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism*; D009435:Synaptic Transmission
D008563:Membrane Lipids; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016718:Arachidonic Acid; D010740:Phospholipases