Abnormal vibrissa‐related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics

Abstract

A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the in barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics’ avoidance of the closed arms in the plus maze.

Targeted deletion of GD3 synthase protects against MPTP‐induced neurodegeneration

“…For unbiased stereological quantification of TH-positive cells, neurons in every fourth section through the rostro-caudal extent of the substantia nigra pars compacta (SNc) were counted in 6–12 sections (mean 8.5) from four mice per group using the optical fractionator method and Stereo Investigator software (MBF Bioscience, Williston, VT) as previously described (Dhanushkodi et al , 2013; Flanigan et al , 2014; Maiti et al , 2016). After delineation of the SNc at low magnification (4x objective), a point grid was overlaid onto each section.…”

MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function

“…Based on the these parameters and counts, the total number of TH-positive cells per selected region were counted using the optical fractionator formula N = 1/ssf × 1/asf × 1/hsf × Q , where ssf is the section sampling fraction, asf is the area sampling fraction, hsf is the height sampling fraction (dissector height divided by the section thickness after shrinkage), and Q denotes the total count of particles sampled for each region. After counting TH+ neurons, slides were counter-stained with cresyl violet (CV), and all SNc neurons positive for CV but negative for TH were counted stereologically, as previously described [12,33]. …”

Differential proteomic and behavioral effects of long-term voluntary exercise in wild-type and APP-overexpressing transgenics

“…zone surrounding the former platform location was used as a measure of memory during the probe trial. This zone score was used as a more accurate measure of memory, compared to quadrant time (Bernardo et al, 2007; Dhanushkodi and McDonald, 2011; Flanigan et al, 2014; Harrison et al, 2009a). Because of the shape of the pool quadrants, some locations within the target quadrant are farther away from the platform location than other locations in neighboring quadrants.…”