Molecular mechanisms of short-term habituation in the leech Hirudo medicinalis.

Although habituation is ubiquitous in the animal kingdom, its underlying mechanisms remain poorly understood. In this study, we began to explore the molecular cascades underlying short-term habituation in the leech Hirudo medicinalis. In H. medicinalis, a training paradigm, consisting of low-frequency repetitive electrical stimulation of the skin, produces a gradual increase in the latency to swim that spontaneously recovers within 20-30 min. As first step in determining the molecular pathways in short-term habituation, we examined the role of Ca(2+). Both Ca(2+) influx through voltage-gated channels and Ca(2+) release from intracellular stores were found to contribute to short-term habituation. The analysis of the downstream targets of elevated cytosolic Ca(2+) revealed that the activation of the phosholipase A(2) was required for the induction of short-term habituation. Finally, we reported that the recruitment of arachidonic acid metabolites, generated by the 5-lipoxygenase pathway, was also necessary for the induction of swim induction habituation. These results provide the framework for a comprehensive characterization of the molecular underpinnings of habituation. This outcome will allow us to compare the mechanisms of habituation with those underlying other forms of nonassociative learning in the leech, such as sensitization and dishabituation, and, more in general, with those governing habituation in different vertebrate and invertebrate model systems.