Mechanisms producing time course of cerebellar long-term depression

Cerebellar long-term depression (LTD) is induced by short-lasting synaptic activities, progressively expressed, and then maintained for hours or longer. Short-lasting events, such as calcium transients, are activated and required for the induction of LTD. Further, a positive-feedback kinase loop was shown to follow the transient events and to aid the transition between LTD induction and prolonged synaptic depression. Yet, it is not entirely clear as to how LTD is maintained and how the maintenance mechanisms are activated, mainly because of a lack of experimental studies regarding this topic, while an idea has been theoretically proposed. A new analysis of the experimental results suggests that early maintenance mechanisms display a threshold behavior and that they may be of stochastic nature. This suggestion is conceptually consistent with an idea from a computational study, which postulates that other bistable switch systems are required for LTD maintenance. We thus propose that cellular mechanisms showing a threshold behavior and a stochastic nature maintain LTD, and that future experimental studies in search of such mechanisms would be an important step toward fully understanding the time course of LTD.