Date of Award
Program or Major
Doctor of Philosophy
Robert G Mair
Human amnesia has been attributed to diencephalic lesions produced by Wernicke-Korsakoff syndrome, tumor, trauma and infarct. Rodent models of diencephalic amnesia suggest the involvement of three anatomic systems, namely the nuclei of the brainstem and diencephalon, the mammillary bodies, and the mediodorsal nucleus of the thalamus. In recent years our laboratory has investigated these systems. Only radiofrequency (RF) lesions of the thalamus involving lateral portions of the internal medullary lamina (L-IML) and including the mediodorsal nucleus (MDn) of the thalamus have disrupted measures of learning and memory in a manner that is qualitatively similar to that seen in human Korsakoff amnesics.
The purpose of the experiments reported here was to further examine the neurologic basis of these deficits. The effects of RF lesions of the L-IML were compared to lesions restricted to two areas of prefrontal cortex (PFC) found to be denervated by the L-IML lesion, i.e. the shoulder of the medial wall (MW) and the cortex dorsal to the rhinal sulcus (RS). Memory was assessed with three tasks: the radial arm maze (RAM), spatial serial reversal (SSR), and spatial delayed nonmatching to sample (DNMTS) tasks. Also, Wheat Germ Agglutinate - Horseradish Peroxidase (WGA-HRP) analyses were done to verify the extent to which MDn projections to PFC were affected by these lesions.
Rodents with lesions of the L-IML were impaired on all three tasks, performing significantly worse than the cortical groups on RAM and DNMTS. Although they committed more errors during initial learning of SSR, like MWs and RSs they exhibited a preserved capacity to perform this task, and demonstrated positive transfer. The PFC groups were impaired only on DNMTS, suggesting that neither of these areas alone can account for the full complement of deficits observed in animals with L-IML lesions. WGA-HRP analyses verified that neither prefrontal lesion interrupted pathways from the thalamus to the other prefrontal area, indicating that these lesions successfully destroyed most of the intended targets.
Harrison, Loredana Maggiora, "The role of thalamo-frontocortical mechanisms in measures of spatial learning and memory" (1992). Doctoral Dissertations. 1707.