Evidence that Arachidonic Acid Plays a Role in Long-Term Potentiation

Abstract

Since its original description by Bliss and Lomo in 1973 [1], long-term potentiation (LTP) in the hippocampus has received a good deal of attention largely because it is considered to be a possible biological substrate for learning and memory. LTP is a remarkable form of synaptic plasticity which describes a long lasting change in synaptic efficacy following a brief train of high-frequency stimulation. Although the molecular mechanisms underlying induction and maintenance of LTP are actively debated, it is generally accepted that the trigger for induction is an increase in postsynaptic Ca2+ concentration arising from increased Ca2+ influx through the N-methyl-d-aspartate (NMDA)-associated Ca2+ channel [2]. At the time of the high-frequency train, glutamate is released from the presynaptic terminal and binds to postsynaptic NMDA (and non-NMDA) receptors. The coincident occupation of the NMDA receptor together with strong depolarization of the postsynaptic membrane relieves the Mg2+ block on the NMDA-associated Ca 2+ channel and allows influx of Ca2+; the subsequent change in Ca2+ concentration triggers LTP. Although there is no consensus of opinion on mechanisms underlying maintenance of LTP, there is a good deal of evidence suggesting that a persistent increase in glutamate release accompanies LTP in dentate gyrus granule cell synapses [3–5]. The increase in release of glutamate has been shown to be inhibited when induction of LTP is blocked by commissural stimulation [3], perfusion of (-)2-amino-5-phosphonopentanoate (AP5; [4]) or nordihydroguaiaretic acid (NDGA; [5]). These observations which indicate that maintenance of LTP is dependent, at least in part, on presynaptic mechanisms, have received support from two of the quantal analysis studies reported in recent months [6, 7].