, 2012). Different patterns of synapse activation can lead to protein synthesis-dependent or -independent plasticity (Govindarajan et al., 2011). However, the importance and mechanism of specific protein translation remains to be examined in this cooperativity. Since there are mRNAs that are differentially distributed in the length of the dendrites, it is tempting to speculate that there is a role for protein synthesis in regulating the

functional compartment in dendrites and spines. Thus, while it is clear that protein synthesis occurs in the dendrite and that it is regulated by neuronal activity, the extent to which the activity of single synapses or synaptic regions stimulates protein synthesis, or alters protein localization, remains unknown. Apoptosis inhibitor Moreover, the importance and impact of synapse location along the dendrite or axon for protein synthesis selleckchem is unknown. In the small cytoplasmic volume of a dendritic spine or growth cone, there is a limit to the amount of protein that can fit into the space before molecular crowding becomes a problem. While it is clear that changes in synaptic transmission involve extensive

regulation of the synaptic proteome via the regulated synthesis and degradation of proteins (Fonseca et al., 2006 and Wang et al., 2009), it is not well understood how these two processes are coordinately regulated to achieve the desired level of individual proteins at synapses. Indeed, this is another level of homeostatic control that must exist in order for synapses to maintain the desired level of receptors, scaffolds, and signaling molecules. Changes in the steady-state level of a protein have to be particularly fast and fine-tuned in neurons, due to the fast Ketanserin nature of synaptic transmission and the rapid induction of plasticity. How are specific mRNAs translated and not others? Studies using either global activity manipulations (TTX/APV) (Sutton et al., 2004) or application of an D1/D5 agonist (Hodas et al., 2012) have suggested large-scale

(at least ∼100 distinct proteins synthesized) changes in the dendritic proteome. Similarly, global cue stimulation of axons elicits the de novo translation of hundreds of new proteins (Yoon et al., 2012). In these studies, however, the stimulation was applied to the entire network (dish of cultured neurons or brain slice). Under physiological conditions the spatial and temporal profile of synaptic and cue stimulation is on a much finer scale and the translational readout is likely limited. Indeed, we know that different cues can trigger translation of specific subsets of mRNAs in the growth cone (Lin and Holt, 2007). The mechanisms by which specific patterns of synaptic signals (e.g., different frequencies of stimulation, different concentrations or gradients of agonists) and receptor activation lead to activation of the translation machinery are not well understood.