12-lipoxygenase modulates l-type calcium channel-dependent long term potentiation by regulating calcium influx through l-type calcium channels [electronic resource]
Hippocampal long-term potentiation (LTP) is generally believed to underlie learning and the consolidation of memories in the mammalian brain. At CA3-CA1 Schaffer collateral synapses one of two fundamental calcium channels must be recruited for the induction of LTP: the NMDA receptor or the L-type calcium channel (LTCC). Though more than twenty years have passed since the finding that NMDA receptors are required for the induction of rip at CA3-CA1 synapses there is little agreement as to the molecules that mediate and modulate LTP induction. This may be partly due to the failure to discriminate between NMDA-receptor dependent and LTCC-dependent forms of LTP, each of which appears to involve distinct signal transduction and modulatory mechanisms. A previous study from our laboratory demonstrated that 12-lipoxygenase (12LOX) mediates metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD), a form of LTCC-dependent plasticity present in neonates. I therefore tested the hypothesis that 12LOX is a general mediator of LTCC-dependent plasticity at CA3-CA1 synapses by measuring LTCC-dependent LTP in adult hippocampal slices from a 12LOX knockout mouse. Herein I describe that, in contrast to its role as a downstream mediator of LTCC-dependent plasticity in the neonate, 12LOX is a selective upstream modulator of adult LTCC-dependent LTP, an action exerted via its regulation of calcium influx through LTCCs
