, 1977); this remains to be tested. On

the other hand, myelin turnover is suggested by the observation that average internode length decreases with age, shorter Navitoclax in vivo internodes being regarded as a hallmark of remyelination following myelin loss (Lasiene et al., 2009). Perhaps de novo myelination and myelin replacement go on concurrently in different parts of the CNS or within axon tracts, such as the corpus callosum, that contain a mixture of myelinated and unmyelinated axons. If myelin turnover turns out to be commonplace, how neural pathways can cope with continual loss and replacement of oligodendrocytes would need to be understood, because the loss of even one myelin internode has been predicted to cause conduction block (Koles and Rasminsky, 1972, Waxman and Brill, 1978 and Smith et al., 1982). Whether action potentials are blocked or delayed will depend on the geometry of the affected fibers, including internode length and axon diameter (e.g., Bostock and Sears, 1976, Waxman and Brill, 1978 and Bakiri et al., 2010). Nevertheless, given that

one oligodendrocyte usually myelinates many axons, significant Bortezomib clinical trial problems might be anticipated from oligodendrocyte turnover. Perhaps new internodes can intercalate between existing internodes—i.e., remyelination might initiate at nodes of Ranvier and gradually expand lengthwise, pushing aside the existing internodal sheath(s) while maintaining continuity of myelin. This brief discussion exposes gaps in our knowledge of basic myelin dynamics that need to be filled before we can hope to understand myelin maintenance and plasticity. Personal experience tells us that learning a complex motor skill—riding a bicycle, playing a musical instrument, learning a dance step or a sporting activity—requires a great deal of time and practice. On the other hand a motor skill, once learned, is difficult to lose and stays with us throughout our active life. The extended learning experience and long decay time seem consistent with the production

and long-term survival of new cells. Could new myelin formation Digestive enzyme during postnatal life play a part in motor learning? Motor learning is an example of unconscious or “nondeclarative” learning, which includes habituation and classical conditioning (e.g., fear conditioning and Pavlovian conditioning). Nondeclarative learning and memory is an ancient system that is well developed in invertebrate animals—for example, the gill retraction reflex that has been studied in Aplysia and other marine molluscs. Studies of this and related phenomena have established that even very small nervous systems have the capacity to learn and remember past experience and that such memories are an intrinsic part of the circuits involved in the behavioral response, not something that is generated or stored remotely ( Carew and Sahley, 1986).