The Smalheiser group has found that dicer and the Ago homolog eIF2c, both involved in miRNA biogenesis, were expressed in mouse brain synaptic fractions and enriched at post-synaptic densities (PSDs; Lugli et al., 2005; Smalheiser and Lugli, 2009). The findings that NMDA and calcium stimulation of synaptoneurosomes induced calpain-dependent activation of dicer led the authors to propose a model in which (i) glutamate or other neurotransmitter activity at synapses causes a local increase of intracellular calcium levels within the post-synaptic neuron; (ii) this calcium increase needs to be sufficient to activate calpain; (iii) calpain liberates active dicer and eIF2c from the PSDs. Furthermore, the authors postulated that the acute effects of calpain on dicer act as a highly localized, phasic, high-threshold trigger that leads to formation of small RNAs near synapses, which once formed should be relatively long-lasting and subsequently independent of ongoing dicer activity (Lugli et al., 2005). Recent studies in Drosophila and rodents have confirmed the importance of components of the RISC complex at the synapse, which was necessary for the establishment of certain forms of short and
