Plasticity and its Role in Neurological Diseases of the Adult Nervous System.

R ecovery after acute neurological damage, e.g. stroke 1 (Table 1), is believed to involve reorganisa-tion of neural circuitry, which enables non-damaged parts of the brain to appropriate new functions. A pragmatist might reasonably argue that understanding the mechanisms underpinning plasticity is not necessary; the goal for physicians is simply to maximise plasticity and, thereby, speed recovery. However, this simple strategy may not work. Excessive or aberrant plasticity has been proposed to cause diseases (Table 1). Therefore, harnessing plasticity for therapeutic benefit requires an understanding of the process of cortical reorganisation and the underlying cellular mechanisms. Plasticity is greatest in the CNS during developmental 'critical periods' , 2,3 but the capacity for significant plasticity remains in adulthood. 4,5 This article focuses on our understanding of plasticity in adolescent and adult cortex. We discuss the role of plasticity in disease and consider approaches that may be used to enhance or reactivate plasticity. Mechanisms underpinning reorganisation Cortical reorganisation during learning or as a result of disease can be best thought of as a process that involves early functional modifications followed by structural changes that consolidate functional reorganisation (Table 2). Functional modifications typically comprise alterations in synaptic strength possibly due to long-term potentia-tion or long-term depression. 6,7 The ensuing structural changes have been described on multiple spatial scales. The most subtle structural changes occur at existing connections between neurons. The shape of dendritic spines, which form the postsynaptic component of excitatory synapses, may alter with modifications in synaptic strength. Strengthening or weakening of connections can be stored as changes in the number of synapses forming those connections. In contrast, formation of new connections may involve axonal growth and/or dendritic remodelling , which are commonly subsumed under the title 'rewiring'. 8 Large-scale rewiring has been described after damage to the nervous system, 9 but there is limited evidence that it occurs to a marked extent when the nervous system is intact. 10 The difference in propensity for rewiring may simply be one of degree, i.e. nervous system damage induces a more complete alteration in inputs compared with learning, or damage may enable activation of new mechanisms. Finally, neural circuits may remodel as a result of implantation of stem cells into the CNS or incorporation of new neurons following adult neurogenesis. 11 Space restrictions mean that we cannot describe the role of plasticity in all of the conditions listed in Table 1. Instead, we briefly …