The pathologic basis of amnesia is obscure. Diseases that produce amnesia in humans are often accompanied by a number of pathologic alterations, both structural and neurochemical, that have been linked hypothetically with learning and memory impairments. We have focused our research on Korsakoff's syndrome, a common cause of diencephalic amnesia that is believed to result from a subacute bout of thiamine deficiency. In an initial series of experiments, we developed an animal model of this disease, the post thiamine deficiency (or PTD) rat. Our investigations of the PTD model have demonstrated: i. behavioral impairments consistent with global anterograde amnesia; ii. changes in indices of neurotransmitter activity measured in local brain regions; iii. thalamic lesions that resemble those of Korsakoff's syndrome in histologic appearance and in topographic distribution in medial thalamus; iv. a consistent coincidence between the occurrence of medial thalamic lesions and behavioral deficits; and v. a general sparing of other extrathalamic structures that have been implicated as being important for learning and memory. The immediate goal of this proposal is to determine whether thalamic lesions can account for the learning and memory impairments of the PTD rat. This goal will accomplished in two ways. First, we will determine whether comparable behavioral impairments can be produced by experimental lesions in thalamic sites commonly associated with pathology in the PTD model. Second, we will determine if rats subjected to PTD treatment, but protected from thalamic lesions by MK-801 treatment, also have a spared ability to learn tasks requiring representational memory. From a broader perspective, this line of research will build on the results of the PTD studies to address several critical issues concerning the role of thalamic mechanisms in learning and memory, namely: i. identifying critical sites at which thalamic lesions impair learning and memory; ii. determining the nature of learning and memory impairments produced by thalamic lesions; and iii. considering possible interactions between thalamic lesions and neurotransmitter systems in the production of diencephalic amnesia.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Biopsychology Study Section (BPO)
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University of New Hampshire
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Hembrook, Jacqueline R; Mair, Robert G (2011) Lesions of reuniens and rhomboid thalamic nuclei impair radial maze win-shift performance. Hippocampus 21:815-26
Mair, Robert G; Hembrook, Jacqueline R (2008) Memory enhancement with event-related stimulation of the rostral intralaminar thalamic nuclei. J Neurosci 28:14293-300
Bailey, Kathleen R; Mair, Robert G (2006) The role of striatum in initiation and execution of learned action sequences in rats. J Neurosci 26:1016-25
Bailey, Kathleen R; Mair, Robert G (2005) Lesions of specific and nonspecific thalamic nuclei affect prefrontal cortex-dependent aspects of spatial working memory. Behav Neurosci 119:410-9
Zhang, Yueping; Bailey, Kathleen R; Toupin, Margaret M et al. (2005) Involvement of ventral pallidum in prefrontal cortex-dependent aspects of spatial working memory. Behav Neurosci 119:399-409
Bailey, K R; Mair, R G (2004) Dissociable effects of frontal cortical lesions on measures of visuospatial attention and spatial working memory in the rat. Cereb Cortex 14:974-85
Mair, Robert G; Burk, Joshua A; Porter, M Christine (2003) Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex. Behav Neurosci 117:596-605
Mair, Robert G; Koch, Jennifer K; Newman, Julie B et al. (2002) A double dissociation within striatum between serial reaction time and radial maze delayed nonmatching performance in rats. J Neurosci 22:6756-65
Porter, M C; Koch, J; Mair, R G (2001) Effects of reversible inactivation of thalamo-striatal circuitry on delayed matching trained with retractable levers. Behav Brain Res 119:61-9
Burk, J A; Mair, R G (2001) Effects of dorsal and ventral striatal lesions on delayed matching trained with retractable levers. Behav Brain Res 122:67-78

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