These observations were paralleled

by in vitro studies of synaptic plasticity demonstrating a clear requirement for newly synthesized proteins in the long-term modification of synaptic function (see Sutton and Schuman, 2006 for review; Paclitaxel solubility dmso also, Tanaka et al., 2008). This link between protein synthesis and long-term plasticity is most recently reinforced by studies showing that targeted genetic disruption of signaling molecules that regulate protein translation interfere with long-term synaptic or behavioral memories (Costa-Mattioli et al., 2009). The above studies, while indicating a requirement for protein synthesis, do not address the location. We now know dendrites and axons of neurons represent specialized cellular “outposts” that can function with a high degree of autonomy at long distances from the soma, as illustrated by the remarkable ability of growing axons to navigate correctly after soma removal (Harris et al., 1987) or isolated synapses to undergo plasticity (Kang and Schuman, 1996 and Vickers et al., 2005). The identification of polyribosomes at the base or in spines (Steward

and Levy, 1982) together with metabolic labeling experiments that provided the first evidence of de novo synthesis of specific proteins in axons and dendrites (Feig and Lipton, 1993, Giuditta et al., 1968, Koenig, 1967 and Torre and Doxorubicin Steward, 1992) indicated the competence of these compartments for translation. Subsequent studies demonstrated

that specific subsets of mRNAs localize to synaptic sites (Steward et al., 1998) and directly linked synaptic plasticity with local translation in dendrites (Aakalu et al., 2001, Huber et al., 2000, Kang and Schuman, 1996, Martin et al., 1997 and Vickers et al., 2005), providing definitive proof that dendrites are a source of protein during plasticity. In axons, the idea of local protein synthesis has been slower to find acceptance, no doubt hindered by the classical view of axons as information transmitters rather than receivers; so, why would local protein synthesis be required? Although ribosomes were identified in growth cones in early ultrastructural studies (Bunge, 1973 and Tennyson, TCL 1970), they were rarely observed in adult axons. It is now thought that at least part of the explanation for their apparent paucity lies in their localization close to the plasma membrane in axons (Sotelo-Silveira et al., 2008) where ribosomal subunits can associate directly with surface receptors (Tcherkezian et al., 2010). In addition, evidence indicates that myelinated axons can tap into an external supply of ribosomes by the translocation of ribosomal proteins from Schwann cells (Court et al., 2011). Growing and navigating axons are clearly information receivers, like dendrites, since their growth cones steer using extrinsic signals.