Abnormal vibrissa‐related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics. (22nd April 2014) - Flanigan, T. J.
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 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 . Abstract : Whiskerless 5xFAD transgenics behave normally in the first 90 seconds of the plus‐maze session. The whiskers of 5xFAD transgenic and wild‐type mice were snipped at 14 months of age. A small group of age‐matched mice with a full complement of whiskers served as controls. (a, c) Whiskered wild‐type mice spent more time on the closed arms and tended to habituate to the closed arms as the session progressed, whereas the whiskered transgenics persisted in avoiding the closed arms. (b, d) The behavior of whiskerless 5xFAD transgenics in the first 90 seconds of the session was indistinguishable from that of wild‐type mice, and genotype differences were attributable to behavior later in the session when wild‐type mice habituated to the closed arms.