Amyloid Deposition and Dendritic Complexity of Corticocortical Projection Cells in Five Familial Alzheimer's Disease Mouse. (21st February 2023)

• Record Type: Journal Article
• Authors: Plachez, Celine; Tsytsarev, Vassiliy; Zhao, Shuxin; Erzurumlu, Reha S.
• Is Part Of: Neuroscience. Volume 512(2023)
• Page Start: 85
• Page End: 98
• Publication Date: 2023-02-21
• Subjects: Alzheimer's disease -- layer 3 pyramidal cells -- motor cortex -- prelimbic cortex -- somatosensory cortex -- voltage-sensitive dye imaging; 5xFAD five FAD mutations -- AAV Adeno-associated viral -- ACSF artificial cerebrospinal fluid -- AD Alzheimer's disease -- AD/ADRD Alzheimer's disease and related dementias -- APP Amyloid precursor protein -- Aβ amyloid beta -- CCP corticocortical projection -- CO cytochrome oxidase -- DAPI 4′, 6-diamidino-2-phenylindole -- FAD Familial Alzheimer's Disease -- M1 primary motor cortex -- NDS normal donkey serum -- NMDA N -methyl-D-aspartate -- PBS phosphate buffered saline -- PFC prefrontal cortex -- PS-1 presenilin-1 -- PS-2 presenilin-2 -- RT room temperature -- S1 primary somatosensory cortex -- ThS Thioflavin S -- VGlut-2 vesicular glutamate transporter 2 -- VSDi voltage-sensitive dye imaging -- ROI Region of interest; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2022.12.013
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Voltage-sensitive dye imaging of whisker activity in 5xFAD somatosensory cortex. Layer 3 pyramidal cell dendritic complexity in 5xFAD mouse cortex. Amyloid deposition in 5xFAD mouse cortex. Abstract: In Alzheimer's disease and related dementias, amyloid beta (Aβ) and amyloid plaques can disrupt long-term synaptic plasticity, learning and memory and cognitive function. Plaque accumulation can disrupt corticocortical circuitry leading to abnormalities in sensory, motor, and cognitive processing. In this study, using 5xFAD (five Familial Alzheimer's Disease – FAD – mutations) mice, we evaluated amyloid plaque formation in different cortical areas, and whether differential amyloid accumulation across cortical fields correlates with changes in dendritic complexity of layer 3 corticocortical projection neurons and functional responses in the primary somatosensory cortex following whisker stimulation. We focused on three cortical areas: the primary somatosensory cortex (S1), the primary motor cortex (M1), and the prefrontal cortex (PFC including the anterior cingulate, prelimbic, and infralimbic subdivisions). We found that Aβ and amyloid plaque accumulation is not uniform across 5xFAD cortical areas, while there is no expression in littermate controls. We also found that there are differential layer 3 pyramidal cell dendritic complexity changes across the three areas in 5xFAD mice, compared to same age controls, with no apparent relation to differential amyloid accumulation. We used voltage-sensitive dye imaging (VSDi) to visualize neural activity in S1, M1 and PFC following whisker activation. Control mice show normal physiological responses in all three cortical areas, whereas 5xFAD mice only display physiological responses in S1. Taken together our results show that 5xFAD mutation affects the overall dendritic morphology of layer 3 pyramidal cells across sensory-motor and association cortex irrespective of the density and distribution of the Aβ amyloid proteins. Corticocortical circuitry between the sensory and motor/association areas is most likely disrupted in 5xFAD mice as cortical responses to whisker stimulation are altered.