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. Author manuscript; available in PMC: 2014 Jan 17.
Published in final edited form as: Nature. 2013 Jan 17;493(7432):327–337. doi: 10.1038/nature11860

Figure 2. Neuronal activity regulates mRNA translation and synaptic plasticity.

Figure 2

At the excitatory synapse, the cell adhesion molecules neurexin and neuroligin and structural proteins in the postsynaptic density, including Shank proteins, regulate, and are regulated by, neuronal activity-dependent signalling networks. The excitatory neurotransmitter glutamate binds NMDA receptors (NMDAR), AMPA receptors (AMPAR) and mGlu receptors (mGluRs). AMPA receptors mediate the fast excitatory neurotransmission. UBE3A degrades Arc, which regulates trafficking of AMPA receptors. During plasticity, activation of NMDA receptors triggers calcium-dependent signalling at the synapse, stimulating CaMKII and modifying AMPA receptor function and actin reorganization. Activation of mGluR triggers several signalling cascades, including the PI(3)K–AKT–mTOR pathway, the Ras–MAPK pathway, and PLC to regulate mRNA translation. FMRP inhibits mRNA translation, and mGluR signalling can regulate FMRP activity. Growth factors, including BDNF, whose expression is induced by neuronal activity, bind receptor tyrosine kinases (including TrkB) that activate multiple signalling pathways, including the PI(3)K–AKT pathway. The PI(3)K–AKT pathway when activated leads to phosphorylation of the TSC1–TSC2 complex to control mTOR activity. Mutations in neurexins, neuroligins, SHANK, GKAP, UBE3A, FMRP and TSC1–TSC2 are associated with ASD.