PLASTICITY AND GROWTH-FACTORS IN INJURY RESPONSE

The central nervous system (CNS) possesses a well-known capacity for c ircuitry rearrangement, or ''plasticity,'' which is maintained through out life. Two well-studied categories of CNS plasticity are the circui try rearrangement which occurs in response to injury and that which oc curs in response to normal environmental stimuli. in an injury respons e, such as that which follows partial denervation of the hippocampus b y unilateral removal of the entorhinal cortex, undamaged fibers in the denervated zone sprout and form new connections to replace lost synap ses. In addition, rearrangement of circuitry also takes place in nonde nervated zones which are functionally associated with the denervated c ircuitry. These observations indicate that the CNS is capable of major remodeling of neuronal circuitry, both in response to an injury as we ll as in the absence of a direct insult. Importantly, such plasticity reactions after injury appear to mediate recovery of lost function in hippocampal-dependent learning. Plasticity can also occur in response to relatively subtle stimuli, such as are found in an enriched environ ment or with exercise. Even tightly structured repetitive exercise, su ch as wheel-running by rats, drives plasticity responses in brain regi ons such as the hippocampus, cortex, and cerebellum. Plasticity in res ponse to injury and environmentally driven plasticity share similar mo lecular features, such as activation of growth factors, suggesting tha t some molecular events and mechanisms driving circuitry remodeling ar e common to all forms of plasticity. In this review, these two categor ies of CNS plasticity are discussed, using in vivo models to illustrat e remodeling occurring after damage, as well as environmentally driven plasticity. (C) 1998 Wiley-Liss, Inc.