Fig. 1

Some of the main signaling pathways in LTP and LTD. LTP involves (at different synapses) several type of receptors which include NMDA receptor (GluN), voltage dependent calcium channel (VDCC), neurotrophin receptor (trkB), adenosine 2 receptor (A2R) or dopamine receptor (DAR). These receptors activate intracellular signaling pathways with local and/or somatic effects, such as phosphoinositide-3 kinase (PI3K)/Akt, protein kinase A (PKA)/ mitogen activated protein kinases (MAPK), calpain/ striatal enriched protein tyrosine phosphatase (STEP) and calcium calmodulin kinase II (CaMKII) pathways. LTD can be triggered by the activation of, for example, GluN, VDCC and metabotropic glutamate receptors (mGlu), depending of the form of LTD. Calcineurin (PP2B)/protein phosphatase 1 (PP1) associated to Janus kinase 2 (JAK2)/ signal transducers and activators of transcription 3 (STAT3), PI3K/Akt and glycogen synthase kinase 3 (GSK3) are mainly required for GluN dependent LTD whereas mGlu dependent LTD activates mainly phospholipase C (PLC)/Protein Kinase C (PKC) and eukaryotic elongation factor 2 kinase (eEF2K) signaling pathways. Sequence of activation of these pathways and inter-regulation between them are two key features to obtain synaptic plasticity events