DOI: 10.5061/dryad.dbrv15fbk
title: Influence of amyloid pathology on retina and dLGN in 5xFAD mouse model

description: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by
 the formation of amyloid beta plaques and neurofibrillary tangles that
 leads to decreased quality of life due to behavioral, motor, and cognitive
 impairments.  Due to the widespread pathological nature of AD,
 many brain regions are affected by amyloid beta plaques including regions
 important for vision such as the lateral geniculate nucleus (LGN) of the
 thalamus which is critical for relaying signals from the retina to the
 primary visual cortex.  Using a wide range of techniques
 including electrophysiological approaches, in vivo and ex vivo imaging
 methods, and immunohistochemistry in a mouse model with progressing
 amyloidosis (5xFAD), the goal of this study was to determine whether
 AD-like pathology disrupts neuronal and synaptic structure and function in
 the visual system.  In vivo electroretinogram recordings revealed
 photoreceptor dysfunction in the 6- and 9-month-old 5xFAD mice, while
 optical coherence tomography indicated no changes in retinal
 thickness.  In the dorsolateral geniculate nucleus (dLGN), the
 rodent homolog of the primate LGN, we identified decreased densities of
 retinal ganglion cell axon terminals and fewer thalamocortical (TC) neuron
 cell bodies.  No detectable deficits in excitatory synaptic
 function or TC neuron dendritic structure were seen in the dLGN, and
 reflexive visual behavior was also found to be normal in the 5xFAD
 mice.  These results indicate relatively modest amyloid-triggered
 dysfunction in these stages of the visual system suggesting that amyloid
 beta plaque formation may play only a small role in the visual system
 dysfunction seen in AD patients.  These results may also point to
 potential compensatory mechanisms that preserve function of visual
 pathways in the 5xFAD visual system.   
description: Immunofluorescence staining, two-photon confocal microscopy:
 quantifying cell body density, synaptic puncta density
 Scotopic electroretinogram (ERG) recording using Celeris
 Diagnosys small animal ERG system. A- and B-wave amplitudes and
 oscillatory potentials measured offline in ClampFit. 
 Thioflavin-S staining of brain tissue, epifluorescence
 microscopy, quantifying plaque density in ImageJ
 Whole-cell patch-clamp recording from thalamocortical relay
 neurons in dLGN using Axon/Molecular Devices patch-clamp amplifier
 (Multiclamp 700A) and data acquisition (DigiData 1550B, Clampex 10),
 measurement of mEPSCs and mEPSC detection using MiniAnalysis
 (Synaptosoft) Neurobiotin cell fills during patch-clamp
 recording, two-photon confocal imaging, dendritic reconstruction in ImageJ
 using Simple Neurite Tracer, Sholl analysis Mouse
 optomotor response measurements using a custom optomotor measurement
 system
description: # McCool et al. dataset
 [https://doi.org/10.5061/dryad.dbrv15fbk](https://doi.org/10.5061/dryad.dbrv15fbk) ## Description of the data and file structure Assessments of retina and dLGN structure and function in 5xFAD mice with progressing amyloidosis at three ages - 6 month, 9 months, and 12 months. 5xFAD mice were compared to age-matched C57bl6J controls. Assessments included in vivo scotopic electroretinogram, in vivo optical coherence tomography, ex vivo brain slice patch-clamp recording from the dorsolateral geniculate nucleus (dLGN), reconstruction of dLGN relay neuron dendrites, immunofluorescence labeling of retinal ganglion cell axon terminals (vGlut2), dLGN neurons (NeuN), thioflavin-S labeling of amyloid plaques, and optomotor response measurements.  ### Files and variables #### File: McCool\_et\_al\_data.xlsx **Description:** Microsoft Excel file containing relevant measurements in the study, organized by figure. "n/a" is placed in cells without data; in most cases these were because of different sample sizes (# of mice or # of recorded cells) between groups. In OCT data ("Fig. 3"), an entry of "unmeasurable" means that there was a large divergence in measurements between each of three OCT graders and so the measurement was deemed to be "unmeasurable". ##### Variables: * ERG amplitude (a- and b-waves) in uV (micro volts) - "Fig. 1" * ERG oscillatory potential amplitude in uV (micro volts) - "Fig. 2" * Inner retina OCT measurements (RNFL+GCL+IPL) in um (microns) - "Fig. 3" * Outer retina OCT measurements (ONL+ELM) in um (microns) - "Fig. 3" * dLGN amyloid plaque density, in plaques per 10,000 um^2 - "Fig. 4" * dLGN vGlut2 puncta density, in puncta per 1000 um^2 - "Fig. 4"dLGN vGlut2 puncta density * dLGN NeuN+ cell density, in cells/100,000 um^3 - "Fig. 5" * dLGN TC neuron Sholl intersections, in number of intersections at each radius - "Fig. 6" * TC neuron mEPSC amplitude, in pA - "Fig. 7" * TC neuron mEPSC frequency, in Hz (events/second) - "Fig. 7" * Optomotor response spatial frequency tracking, % of time spent tracking - "Fig. 8" * Optomotor response contrast sensitivity tracking, % of time spent tracking - "Fig. 8" **Units:** * uV = micro volts * um = micro meters * um2 = square micrometers * um3 = cubic micrometers * pA = picoamps * Hz = hertz