Pruning of dendrites and restoration of function after brain damage: Role of the NMDA receptor

Abstract

Following unilateral injury to the forelimb-representation area of the sensorimotor cortex (FL-SMC) in adult rats, there occurs a biphasic process of overgrowth and partial elimination of neuronal dendrites in layer V pyramidal cells of the homotopic cortex of the opposite hemisphere. These neural events are associated with hyper-reliance on the non-impaired forelimb for postural-supporting and related movements that compensate for impaired function in the other forelimb. The overgrowth appears to be use-dependent because it can be prevented by one-sleeve casts that restrict the range of movements of the unimpaired limb during the period of expected neural growth. In development, “exuberant” growth of neurons is often followed by pruning, a process that has been associated with activity-dependency and a glutamatergic N-methyl-D-aspartate (NMDA) mechanism. To determine whether a related mechanism might be operating in adult animals recovering from brain damage, MK-801, a non-competitive NMDA receptor antagonist, was administered during the pruning phase in adult rats that had sustained FL-SMC lesions. MK-801 prevented the elimination of dendrites in the FL-SMC rats and had no effect on dendritic arborization in Sham-operated rats. MK-801 reinstated dysfunction in the previously-recovered forelimb in FL-SMC rats, and had no effect in Sham-operated rats. These data are consistent with the possibility that there may be a functionally important pruning mechanism with a glutamatergic component in adults with FL-SMC lesions, just as in the developing brain.