Alteration of dendritic spine morphology in rat prefrontal cortex subsequent to cerebellar dentate nuclei lesions.

摘要

Anatomical tracing studies in primates have revealed neural tracts from the cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in nonmotor processes. Research in our laboratory and others examining the functional role of these tracts in rats has shown that disruption of this cerebellothalamocortical pathway via dentate nuclei lesions leads to visuospatial and motivational deficits in the absence of motoric impairment. As functional deficits likely occur secondary to loss of cerebellar input to cerebral areas necessary for appropriate functional processing, loss of such input to these areas should result in morphological alterations of the cortex. To test this hypothesis, the current study characterized morphological alterations in cerebral prefrontal cortex believed important for visuospatial and motivational processes following bilateral cerebellar dentate nuclei lesions.;Rats received either bilateral electrolytic cerebellar dentate nuclei lesions or sham surgery and then allowed to recover for 30 days. Randomly selected Golgi-impregnated neurons in prefrontal cortex were examined for morphological alterations. It was specifically hypothesized that lesioned rats, as compared to sham rats, would demonstrate distal (2nd+ order) dendritic morphological alterations including decreased average branch length, decreased spine density, and decreased proportion of immature spines.;Measures of branch length revealed no differences between lesioned and sham rats. Spine density did not differ between lesioned and sham rats in either apical or basilar arbors; however, the proportion of immature to mature spines significantly decreased in lesioned rats as compared to sham controls. Specifically, in the basilar arbor, immature spines decreased from a rate of .73 per mature spine to a rate of .49 per mature spine, a change of 33%. Terminal ends in the apical arbor displayed similar results, as immature spines decreased from a rate of .80 per mature spine to a rate of .58 per mature spine, a change of 28%.;Although expected pruning of branches and spines did not occur, these results are consistent with our hypotheses that cerebellar lesions influence prefrontal morphology and support the possibility that functional deficits following cerebellar dentate nuclei lesions are related to prefrontal morphological alteration.