Evidence for synaptic proliferation, reorganization, and growth in the excitotoxic lesioned adult rat caudate nucleus.

Functional recovery following brain injury depends, in part, on the reestablishment of synaptic connections by surviving neurons. In this study we used quantitative methods to examine the synaptic organization of the caudate neuropil at 2, 7, and 30 weeks following excitotoxic injury. Results showed that in regions of severe to moderate neuronal depletion caused by intrastriatal injections of quinolinic acid, synaptic density was significantly reduced relative to controls but was significantly greater than neuronal density (percentage of control) at all postlesion intervals. Moreover, there was a marked increase in synaptic density (percentage of control), but not neuronal density (percentage of control), in the lesion periphery between 7 and 30 weeks postlesion. The relative proportion of axospinous synapses to total synapses was significantly reduced in the center of the lesion at all postlesion intervals but was similar to controls in regions of neuropil that were less severely affected. In the lesion and its borders there was also a significant increase in the proportion of short synaptic contacts between axons and spines and a proliferation of small unmyelinated fibers. Furthermore, after 30 weeks postlesion, regions of severe neuronal depletion developed aberrant synaptic contacts between vesicle-containing profiles which were significantly larger than those in normal caudate. We conclude that excitotoxic lesions of the neostriatum precipitate a variety of responses in injured neuropil including synaptic proliferation, growth, and altered circuitry.