Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice
| Autor: | Jason K. Clark, Jonathon D. Crystal, Ruth Furukawa, Marcus Fechheimer, John J. Wagner, Matthew Furgerson |
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| Rok vydání: | 2015 |
| Předmět: |
Cognitive Neuroscience
Hippocampus Experimental and Cognitive Psychology Mice Transgenic Spatial memory Article Behavioral Neuroscience Mice Alzheimer Disease Neuroplasticity medicine Animals Maze Learning Spatial Memory Memory Disorders Neuronal Plasticity Long-term potentiation medicine.disease Disease Models Animal Memory Short-Term nervous system Synaptic plasticity Synapses NMDA receptor Memory consolidation Alzheimer's disease Psychology Neuroscience |
| Zdroj: | Neurobiology of learning and memory. 125 |
| ISSN: | 1095-9564 |
| Popis: | Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3 month old) 3xTg-AD mice were as impaired in the spatial working memory task as were the older (8 month old) 3xTg-AD mice when compared with age-matched NonTg control animals. Field potential recordings from the CA1 region of slices prepared from the ventral hippocampus were obtained to assess synaptic transmission and capability for synaptic plasticity. At 3 months of age, the NMDA receptor-dependent component of LTP was reduced in 3xTg-AD mice. However, the magnitude of the non-NMDA receptor-dependent component of LTP was concomitantly increased, resulting in a similar amount of total LTP in 3xTg-AD and NonTg mice. At 8 months of age, the NMDA receptor-dependent LTP was again reduced in 3xTg-AD mice, but now the non-NMDA receptor-dependent component was decreased as well, resulting in a significantly reduced total amount of LTP in 3xTg-AD compared with NonTg mice. Both 3 and 8 month old 3xTg-AD mice exhibited reductions in paired-pulse facilitation and NMDA receptor-dependent LTP that coincided with the deficit in spatial working memory. The early presence of this cognitive impairment and the associated alterations in synaptic plasticity demonstrate that the onset of some behavioral and neurophysiological consequences can occur before the detectable presence of plaques and tangles in the 3xTg-AD mouse model of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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