PRUNING OF DENDRITES AND RESTORATION OF FUNCTION AFTER BRAIN-DAMAGE -ROLE OF THE NMDA RECEPTOR

Following unilateral injury to the forelimb-representation area of the sensorimotor cortex (FL-SMC) in adult rats, there occurs a biphasic p rocess of overgrowth and partial elimination of neuronal dendrites in layer V pyramidal cells of the homotopic cortex of the opposite hemisp here. These neural events are associated with hyper-reliance on the no n-impaired forelimb for postural-supporting and related movements that compensate for impaired function in the other forelimb. The overgrowt h appears to be use-dependent because it can be prevented by one-sleev e casts that restrict the range of movements of the unimpaired limb du ring 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 duri ng 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 h ad no effect on dendritic arborization in Sham-operated rats. MK-801 r einstated dysfunction in the previously-recovered forelimb in FL-SMC r ats, and had no effect in Sham-operated rats. These data are consisten t with the possibility that there may be a functionally important prun ing mechanism with a glutamatergic component in adults with FL-SMC les ions, just as in the developing brain.