Low-frequency-induced synaptic potentiation: a paradigm shift in the field of memory-related plasticity mechanisms?

Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity thought to play functional roles in learning and memory processes. It is generally assumed that the direction of synaptic modifications (i.e., up- or down-regulation of synaptic strength) depends on the specific pattern of afferent inputs, with high frequency activity or stimulation effectively inducing LTP, while low-frequency patterns often elicit LTD. This dogma ("high frequency-LTP, low frequency-LTD") has recently been challenged by evidence demonstrating low frequency stimulation (LFS)-induced synaptic potentiation in the rodent hippocampus and amygdala. Extensive work in the past decades has focused on deciphering the mechanisms by which high frequency stimulation of afferent fiber systems results in LTP. With this review, we will compare and contrast the well-known synaptic and cellular mechanisms underlying classical, high-frequency-induced LTP to those mediating the more recently discovered phenomena of LFS-induced synaptic enhancement. In addition, we argue that LFS protocols provide a means to more accurately mimic some endogenous, oscillatory activity patterns present in hippocampal and extra-hippocampal (especially neocortical) circuits during periods of memory consolidation. Consequently, LFS-induced synaptic potentiation offers a novel and important avenue to investigate cellular and systems-level mechanisms mediating the encoding, consolidation, and transfer of information throughout multiple forebrain networks implicated in learning and memory processes. (c) 2009 Wiley-Liss, Inc.