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Alzheimer's pathology causes impaired inhibitory connections and reactivation of spatial codes during spatial navigation.
- Source :
-
Cell reports [Cell Rep] 2021 Apr 20; Vol. 35 (3), pp. 109008. - Publication Year :
- 2021
-
Abstract
- Synapse loss and altered synaptic strength are thought to underlie cognitive impairment in Alzheimer's disease (AD) by disrupting neural activity essential for memory. While synaptic dysfunction in AD has been well characterized in anesthetized animals and in vitro, it remains unknown how synaptic transmission is altered during behavior. By measuring synaptic efficacy as mice navigate in a virtual reality task, we find deficits in interneuron connection strength onto pyramidal cells in hippocampal CA1 in the 5XFAD mouse model of AD. These inhibitory synaptic deficits are most pronounced during sharp-wave ripples, network oscillations important for memory that require inhibition. Indeed, 5XFAD mice exhibit fewer and shorter sharp-wave ripples with impaired place cell reactivation. By showing inhibitory synaptic dysfunction in 5XFAD mice during spatial navigation behavior and suggesting a synaptic mechanism underlying deficits in network activity essential for memory, this work bridges the gap between synaptic and neural activity deficits in AD.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Alzheimer Disease metabolism
Animals
Brain Waves physiology
CA1 Region, Hippocampal metabolism
Disease Models, Animal
Electrodes, Implanted
Humans
Interneurons pathology
Male
Memory physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Pyramidal Cells pathology
Synapses pathology
Synaptic Transmission physiology
Virtual Reality
Alzheimer Disease physiopathology
CA1 Region, Hippocampal physiopathology
Interneurons metabolism
Pyramidal Cells metabolism
Spatial Navigation physiology
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 33882308
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109008