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Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Published on Dec 1, 2019in Scientific Reports 4.01
· DOI :10.1038/s41598-018-37151-z
Alina C Stimmell (FSU: Florida State University), David Baglietto-Vargas21
Estimated H-index: 21
(UCI: University of California, Irvine)
+ 5 AuthorsAaron A. Wilber8
Estimated H-index: 8
(FSU: Florida State University)
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Abstract
In early Alzheimer’s disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks.
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Published on Aug 1, 2018in Aging Cell 7.35
David Baglietto-Vargas21
Estimated H-index: 21
(UMA: University of Málaga),
Gilberto Aleph Prieto3
Estimated H-index: 3
(UCI: University of California, Irvine)
+ 12 AuthorsAlessandra Cadete Martini6
Estimated H-index: 6
(UCI: University of California, Irvine)
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that impairs memory and causes cognitive and psychiatric deficits. New evidences indicate that AD is conceptualized as a disease of synaptic failure, although the molecular and cellular mechanisms underlying these defects remain to be elucidated. Determining the timing and nature of the early synaptic deficits is critical for understanding the progression of the disease and for identifying effective targets for therapeutic inte...
Published on Jun 1, 2018in Journal of Neurophysiology 2.61
James R. Hinman12
Estimated H-index: 12
(BU: Boston University),
Holger Dannenberg3
Estimated H-index: 3
(BU: Boston University)
+ 1 AuthorsMichael E. Hasselmo72
Estimated H-index: 72
(BU: Boston University)
Animals must perform spatial navigation for a range of different behaviors, including selection of trajectories toward goal locations and foraging for food sources. To serve this function, a number of different brain regions play a role in coding different dimensions of sensory input important for spatial behavior, including the entorhinal cortex, the retrosplenial cortex, the hippocampus and the medial septum. This article will review data concerning the coding of the spatial aspects of animal ...
Published on Apr 1, 2019in Nature 43.07
Øyvind Arne Høydal1
Estimated H-index: 1
(NTNU: Norwegian University of Science and Technology),
Emilie Skytøen3
Estimated H-index: 3
(NTNU: Norwegian University of Science and Technology)
+ 2 AuthorsEdvard I. Moser64
Estimated H-index: 64
(NTNU: Norwegian University of Science and Technology)
The hippocampus and the medial entorhinal cortex are part of a brain system that maps self-location during navigation in the proximal environment1,2. In this system, correlations between neural firing and an animal’s position or orientation are so evident that cell types have been given simple descriptive names, such as place cells3, grid cells4, border cells5,6 and head-direction cells7. While the number of identified functional cell types is growing at a steady rate, insights remain limited by...
Published on Mar 21, 2018in The Journal of Neuroscience 6.07
Lawrence Rajendran28
Estimated H-index: 28
(UZH: University of Zurich),
Rosa Chiara Paolicelli11
Estimated H-index: 11
(UZH: University of Zurich)
Microglia are emerging as key players in neurodegenerative diseases, such as Alzheimer9s disease (AD). Thus far, microglia have rather been known as modulator of neurodegeneration with functions limited to neuroinflammation and release of neurotoxic molecules. However, several recent studies have demonstrated a direct role of microglia in “neuro” degeneration observed in AD by promoting phagocytosis of neuronal, in particular, synaptic structures. While some of the studies address the involvemen...
Published on Dec 1, 2017in Nature Communications 11.88
Adrien Peyrache11
Estimated H-index: 11
(Montreal Neurological Institute and Hospital),
Natalie Schieferstein1
Estimated H-index: 1
(Humboldt University of Berlin),
György Buzsáki124
Estimated H-index: 124
Animals integrate multiple sensory inputs to successfully navigate in their environments. Head direction (HD), boundary vector, grid and place cells in the entorhinal-hippocampal network form the brain’s navigational system that allows to identify the animal’s current location, but how the functions of these specialized neuron types are acquired remain to be understood. Here we report that activity of HD neurons is influenced by the ambulatory constraints imposed upon the animal by the boundarie...
Published on Jul 29, 2017in Journal of Alzheimer's Disease 3.70
Sicong Tu14
Estimated H-index: 14
(University of Oxford),
Hugo J. Spiers29
Estimated H-index: 29
(UCL: University College London)
+ 2 AuthorsMichael Hornberger120
Estimated H-index: 120
(UEA: University of East Anglia)
Background: Diagnosis of behavioral variant frontotemporal dementia (bvFTD) can be challenging, in particular when patients present with significant memory problems, which can increase the chance of a misdiagnosis of Alzheimer’s disease (AD). Growing evidence suggests spatial orientation is a reliable cognitive marker able to differentiate these two clinical syndromes. Objective: Assess the integrity of egocentric and allocentric heading orientation and memory in bvFTD and AD, and their clinical...
Published on Jul 1, 2017in Nature 43.07
Eric McDade26
Estimated H-index: 26
,
Randall J. Bateman39
Estimated H-index: 39
Published on Jul 1, 2017in Behavioural Brain Research 2.77
Katherine E. Davis7
Estimated H-index: 7
(University of Manchester),
Kathryn Burnett1
Estimated H-index: 1
,
John Gigg17
Estimated H-index: 17
(University of Manchester)
Abstract Rodent spatial memory is commonly tested using the water-maze; however, there is a potential confound of stress on learning in this behavioural paradigm. This is particularly relevant when testing spatial memory in models of neurodegeneration, such as the 3xTg mouse model for Alzheimer’s disease. Here, we first confirmed that 3xTgAD mice express fear conditioning and then compared the performance of young and middle-aged mice on short-duration versions of the radial arm water-maze (RAWM...
Published on Jun 1, 2017in Trends in Neurosciences 12.31
Stefania Forner2
Estimated H-index: 2
(UCI: University of California, Irvine),
David Baglietto-Vargas21
Estimated H-index: 21
(UCI: University of California, Irvine)
+ 2 AuthorsFrank M. LaFerla84
Estimated H-index: 84
(UCI: University of California, Irvine)
Alzheimer's disease (AD) is characterized by memory loss, cognitive decline, and devastating neurodegeneration, not only as a result of the extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau, but also as a consequence of the dysfunction and loss of synapses. Although significant advances have been made in our understanding of the relationship of the pathological role of Aβ and tau in synapse dysfunction, several questions remain as to how Aβ and tau int...
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