Abstract
Alzheimer’s disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer’s disease shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex. However, it is not known how degeneration disrupts intrinsic forms of brain plasticity. Here we characterised the impact of tauopathy on a simple form of intrinsic plasticity in the visual system, which allowed us to track plasticity at both long (days) and short (minutes) timescales. We studied rTg4510 transgenic mice at early stages of tauopathy (5 months) and a more advanced stage (8 months). We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days. We found that both short- and long-term visual plasticity were already disrupted at early stages of tauopathy, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. Additionally, visually evoked behaviours were disrupted in both younger and older mice expressing mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy. This simple measure of plasticity may help understand how tauopathy disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.
Highlights
Alzheimer’s disease and other dementias are thought to underlie a progressive impairment of neural plasticity
Mice fed a normal diet, and continuing to express the mutant tau showed increased tau pathology (F = 23.61, p = 10−4, two-way ANOVA, Fig. 1b, Supplementary Fig. 1) and a significant reduction in the overall brain weight compared to Tau− animals (F = 5.79, p = 0.02, Fig. 1b)
We found that the amplitude of the visual evoked potential (VEP) was similar in 5-month old Tau− and Tau+ animals (Fig. 1d)
Summary
Alzheimer’s disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer’s disease shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex It is not known how degeneration disrupts intrinsic forms of brain plasticity. We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days We found that both short- and long-term visual plasticity were already disrupted at early stages of tauopathy, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. We found that basic visual evoked responses were largely unaffected, even at late stages of tauopathy, consistent with previous reports[9] Both short- (intra-day) and long-term (inter-day) visual plasticity were disrupted, even at early stages of tauopathy. Visual plasticity may provide a potential target for detecting dementias at early stages of the disease, in humans as well as in animal models
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