A novel NO-dependent 'molecular-memory-switch' mediates presynaptic expression and postsynaptic maintenance of LTP in the octopus brain

The octopus brain shows a robust hippocampal-like activity-dependent LTP, which is NMDA-independent, yet associative and presynaptically expressed and, as shown here, also independent of protein synthesis. Have the molecular mechanisms for mediating this LTP evolved independently or have they converged? Here we report on a distinctive adaptation of the nitric-oxide (NO) system for mediation of the octopus LTP. Unlike the suggested role of NO in LTP induction in the hippocampus, in octopus, inhibitors of NO-synthase (NOS) did not block LTP induction but either 1) reversibly erased LTP expression, suggesting that a constitutive elevation in NO mediates the presynaptic LTP expression or 2) reversed LTP induction and maintenance because a second LTP could be induced after inhibitor washout. We therefore propose a protein synthesis-independent molecular-switch, whereby NO-dependent NOS reactivation maintains NOS in its active state. Thus, while the octopus LTP shows marked evolutionary convergence with LTP in vertebrates, an extreme molecular novelty has evolved to mediate it.