ReviewMultiple cellular cascades participate in long-term potentiation and in hippocampus-dependent learning

- Different signaling cascades are activated by different parameters of stimulation.
- Calpain-1 activation is required for TBS-induced LTP.
- Calpain-2 activation following TBS limits the extent of LTP.
- Signaling cascades converge onto a common set of downstream effectors.
- Cross-talks between cascades lead to multiple forms of LTP.

Since its discovery by Bliss and Lomo, the phenomenon of long-term potentiation (LTP) has been extensively studied, as it was viewed as a potential cellular mechanism of learning and memory. Over the years, many signaling cascades have been implicated in its induction, consolidation and maintenance, raising questions regarding its real significance. Here, we review several of the most commonly studie signaling cascades and discuss how they converge on a common set of mechanisms likely to be involved in the maintenance of LTP. We further argue that the existence of cross-talks between these different signaling cascades can not only account for several discrepancies in the literature, but also account for the existence of different forms of LTP, which can be engaged by different types of stimulus parameters under different experimental conditions. Finally, we discuss how the understanding of the diversity of LTP mechanisms can help us understand the diversity of the types of learning and memory.This article is part of a Special Issue entitled SI: Brain and Memory.