There is no accepted treatment for amnesia. Although it is now accepted that medical diencephalic lesions can produce sever amnesia in humans, the specific neural pathways that must be damaged to impair memory have not yet been identified. This proposal is continue work on an animal model of Korsakoff's disease, a common cause of diencephalic amnesia that is though to be caused by thiamine deficiency. Our earlier work showed that pyrithiamine-induced thiamine deficiency (PTD) in the rate can produce lesions in diencephalic structures that are commonly affected by Korsakoff's disease. Behavioral studies provided evidence that PTD treatment in rats, like Korsakoff's disease in humans, affects measures of working memory while apparently sparing the capacity for reference memory. In the current period of funding, the lateral portion of the internal medullary lamina of thalamus (the L-IML site) was identified as the critical site of pathology that can account for the behavioral deficits of PTD-treated rats. The immediate goal of this proposal is to compare the effects of lesioning the two major systems that are disrupted by lesions of the L-IML site: the specific projections of the mediodorsal thalamic nucleus to frontal cortex and the non-specific intralaminar nuclei. This goal will be accomplished by a series of experiments comparing the effects of discrete thalamic and frontal cortical lesions on measures of working memory that have been found to be impaired by radiofrequency lesions of the L-IML site. The long range goals of this research are: i. to determine the neurological basis of diencephalic amnesia; ii. to develop an animal model of diencephalic amnesia with sufficient neurological validity to allow meaningful studies of the restitution of memory function in amnesia.
NIH ExPorter
NIH ExPorter