Unrecognized potential of surviving neurons: Within-systems plasticity, recovery of function, and the hypothesis of minimal residual structure

When brain structures are incompletely injured, even a very small number of surviving neurons is sufficient for recovery of the lost functions to occur. Several examples are presented: 1) After partial lesions of the adult rat optic nerve an initial, complete blindness is followed, within a few weeks, by significant recovery of visual functions to near-normal levels. This is possible despite the presence of only about 10% of surviving retinal ganglion cells. 2) In Parkinson's disease, clinical signs manifest only when more than 70%-80% of the dopamine (DA)-containing cells are lost. When the lesion is greater than about 95%, locomotor performance can no longer be compensated, but with the implantation of as little as 5%-10% of the original DA-cell number, significant motor improvements may be achieved. 3) Similarly, in spinal cord-injured rats, recovery of locomotor performance is still observed in animals with lesions greater than 95% where only a small rim of tissue survives the injury. It is therefore proposed that a certain ''minimal residual structure'' (MRS), often 10% or less, is required for functions to recover following CNS injury. In the context of this ''within-systems'' plasticity, the MRS-hypothesis emphasizes the role of spared neuronal tissue in brain plasticity and points to an unrecognized potential of residual neurons to contribute to recovery of function. Future therapeutic studies should make use of behavioral assays ''at threshold,'' in which the MRS is defined so as to avoid the inappropriate rejection of potentially useful therapeutic strategies.