Date of Award
Program or Major
Doctor of Philosophy
Robert G Mair
The most common cause of diencephaic amnesia in human is Wernicke-Korsakoff's disease, the psychological component of a nutritional polyneuropathy associated with chronic alcoholism. It has long been understood that Wernicke-Korsakoff's disease is caused by thiamine deficiency. The symptoms of the acute Wernicke's phase of this disease include disorientation, ataxia, and ocular nystagmus, and if left untreated, death. If treated with thiamine, the acute symptoms quickly subside. However, following recovery from the acute Wernicke's symptoms, many patients evidence the symptoms of the chronic Korsakoff's syndrome, which includes both global anterograde and retrograde memory deficits and personality changes. The memory deficits observed in humans Korsakoff's patients are coincident with the observation of lesions to the medial thalamic structures of the brain.
The fact that Wernicke-Korsakoff's is caused by thiamine deficiency has led to the development of animal models of diencephalic amnesia. The purpose of the experiments reported here was to examine the extent to which the behavioral deficits observed in the post-thiamine deficiency (PTD) rat paralleled the learning and memory deficits observed in human Korsakoff's patients. Following treatment with the thiamine antagonist pyrithiamine and a thiamine free diet, PTD animals were tested on a series of behavioral tasks using spatial, auditory, and olfactory stimuli. PTD rats were first compared with controls for evidence of multisensory discrimination and reversal learning deficits as a test of global amnesia. Second, using the spatial representational memory task, match-to-sample, PTD animals were tested for evidence of anterograde memory deficits. Finally, using a pretrained spatial nonmatch-to-sample task, PTD rats were tested for evidence of retrograde memory deficits. The brains of the PTD animals were then removed and examined for evidence of the Korsakoff's neuropathy.
The results of these experiments support the PTD rat as an animal model of diencephalic amnesia. PTD animals had showed behavioral deficits that extended across sensory modalities and could be characterized as anterograde and retrograde in nature. Histological analysis of the brains of PTD animals showed consistent lesions of the medial aspect of the thalamas, thus supporting the hypothesis that this is the critical lesion responsible for the memory deficits observed in Korsakoff's syndrome.
Knoth, Russell Laine, "Multisensory discrimination and representational memory deficits in post-thiamine deficient rats: Testing an animal model of human Wernicke-Korsakoff's Disease" (1988). Doctoral Dissertations. 1562.