Corticothalamic dysfunction and cognitive deficits in a mouse model of Alzheimer's disease

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Presented at: Society for Neuroscience annual meeting in New Orleans, LA Oct 12-17, 2012

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive decline as well as a 5-10 fold increase in seizure incidence.

Although seizures were once thought to be secondary to disease, recent experiments suggest they may contribute to cognitive deficits early in disease progression. To investigate the underlying mechanisms, we use transgenic mice overexpressing human amyloid precursor protein (APP) bearing mutations that result in high levels of Aβ production. The type of seizures exhibited by APP mice suggests involvement of the corticothalamic network.

The corticothalamic network regulates a number of brain functions, including attention, learning and memory, cortical processing, and sleep maintenance which are all also affected in AD. To determine whether this network is indeed dysregulated in APP mice, we mapped activity in specific components of the corticothalamic network by assessing the expression and distribution of neuronal activity markers. We found decreased activity in an inhibitory thalamic control nucleus, and associated disinhibition of thalamic relay nuclei that project to hippocampal and cortical regions. APP mice also exhibited disturbances in sleep/wake patterns that were consistent with dysregulation of corticothalamic activity and were associated with hippocampal memory deficits. Thus, corticothalamic dysfunction may be a common denominator in AD pathophysiology and deserves further investigation.

Recommended citation: Corbett B, Zhang X, Zhao L, and Chin J (2012) Corticothalamic dysfunction and cognitive deficits in a mouse model of Alzheimer's disease. Soc for Neurosci Abstr 343.12.

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