Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo
| Autor: | Katherine J. Kopeikina, Brian J. Bacskai, Bradley T. Hyman, Susanne Wegmann, Kishore V. Kuchibhotla, Mark L. Andermann, Nikita Rudinskiy, Tara L. Spires-Jones, Jonathan M. Hawkes |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Neurological Tau protein Mice Transgenic tau Proteins Biology Mice Calcium imaging Alzheimer Disease Image Processing Computer-Assisted medicine Animals Humans Transgenes Cognitive decline Neurons Photons Multidisciplinary Neurodegeneration Brain Neurofibrillary Tangles Neurofibrillary tangle Dependovirus Biological Sciences medicine.disease Somatodendritic compartment Microscopy Fluorescence Tauopathies Mutation biology.protein Calcium Alzheimer's disease Neuroscience Frontotemporal dementia |
| Zdroj: | Kuchibhotla, K V, Wegmann, S, Kopeikina, K J, Hawkes, J, Rudinskiy, N, Andermann, M L, Spires-Jones, T L, Bacskai, B J & Hyman, B T 2014, ' Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo ', Proceedings of the National Academy of Sciences, vol. 111, no. 1, pp. 510-4 . https://doi.org/10.1073/pnas.1318807111 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1318807111 |
| Popis: | Alzheimer's disease (AD) is pathologically characterized by the deposition of extracellular amyloid-β plaques and intracellular aggregation of tau protein in neurofibrillary tangles (NFTs) (1, 2). Progression of NFT pathology is closely correlated with both increased neurodegeneration and cognitive decline in AD (3) and other tauopathies, such as frontotemporal dementia (4, 5). The assumption that mislocalization of tau into the somatodendritic compartment (6) and accumulation of fibrillar aggregates in NFTs mediates neurodegeneration underlies most current therapeutic strategies aimed at preventing NFT formation or disrupting existing NFTs (7, 8). Although several disease-associated mutations cause both aggregation of tau and neurodegeneration, whether NFTs per se contribute to neuronal and network dysfunction in vivo is unknown (9). Here we used awake in vivo two-photon calcium imaging to monitor neuronal function in adult rTg4510 mice that overexpress a human mutant form of tau (P301L) and develop cortical NFTs by the age of 7-8 mo (10). Unexpectedly, NFT-bearing neurons in the visual cortex appeared to be completely functionally intact, to be capable of integrating dendritic inputs and effectively encoding orientation and direction selectivity, and to have a stable baseline resting calcium level. These results suggest a reevaluation of the common assumption that insoluble tau aggregates are sufficient to disrupt neuronal function. |
| Databáze: | OpenAIRE |
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