Mechanisms of translation regulation in long-term synaptic plasticity
Memories are encoded in the unique configurations of the vast neuronal networks of the brain. Each of these connections possesses the ability to be modified. Such long-lasting changes at the synapse often require the synthesis of new proteins that create what we call memory traces. Evidence suggests that the signal-induced activation of translation in some forms of synaptic plasticity occurs locally, at the activated synapses, rather than in the soma. However, the mechanisms regulating local and rapid de novo protein synthesis are poorly understood. The initiation step of translation is a highly regulated step and is believed to be the main target of control. The present research project challenges this view for a certain form of long-term synaptic plasticity, metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD). We show, using electrophysiological recordings of dissociated hippocampal neurons in cultures coupled to pharmacological inhibitors, that translation regulation depends on elongation and termination, rather than initiation. Moreover, by exploiting RNA knockdown strategies, we demonstrate that the RNA-binding protein Staufen 2 plays a crucial role in mGluR-LTD induced in cultures. Altogether, the findings of the present study support a model of translation regulation that is downstream of initiation.
mGluR-LTD protein synthesis translation regulation RNA-binding proteins Staufen 2