vation of MEK (Mitogen-Activated Protein Kinase/

vie nd g er a 5-methyl-4-isoxazolepropionic acid receptors (AMPARs) into and out of synapses. Increases in synaptic AMPARs loop that transforms the initial transient signal into a long-term response that can last for hours or longer Erkens et al. Molecular Brain (2015) 8:1 DOI 10.1186/s13041-014-0092-8PKC-mediated RKIP phosphorylation thus triggers theNetherlands Full list of author information is available at the end of the articleresult in long-term potentiation of synaptic strength and AMPAR removal in long-term depression (LTD) [1,2]. In the cerebellum, Purkinje cells (PCs) represent the key output cells that respond to excitatory synaptic signals coming from both parallel fibers (PFs) and climbing fi-bers (CFs) [3,4]. LTD at the PC synapse occurs upon simultaneous firing of PF and CF [5,6]. CF activity causes [13]. Computational predictions [14,15] and recent ex-perimental studies in cerebellar slices [13,16] have estab-lished the key molecular players within this feedback loop (Figure 1). Briefly, the Ca2+ levels that occur during LTD induction activate protein kinase C (PKC), which in turn phosphorylates the Raf kinase inhibitory protein (RKIP). In the unphosphorylated state, RKIP sequesters c-Raf thereby preventing its interaction with and acti