Cortical Plasticity Deficit in the Visual System of Alzheimer’s Disease Transgenic Mice

Abstract

Cerebral plaques and neurofibrillary tangles are common markers associated with Alzheimer’s disease.  Cerebral plaques are due to the aggregation of a particular peptide product following the proteolytic cleavage of amyloid precursor protein (APP)—amyloid-β peptide (Aβ). Equally important in the pathogenesis of AD are the mutant Presenilin genes—the most common features observed in individuals diagnosed with early-onset AD.  These effects have been extensively examined in aging mice in previous studies, using APP/PS1 transgenic mice co-expressing the Swedish mutant allele of APP (APPswe) and an exon 9-deleted allele of Presenilin 1 (PSEN1ΔE9).    However, whether these genes play a role in normal plasticity earlier in life (i.e. before the onset of plaque formation) has not been studied previously. We subjected both wild type and transgenic mice to four days monocular deprivation (MD) during the critical period of visual development in the mouse species. Using widefield epifluorescence before and after MD, we measured ocular dominance plasticity (ODP) in juvenile wild type and APP/PS1 transgenic mice. To achieve this goal, we complemented ex vivo paradigms with an in vivo approach. Specifically, we used intrinsic signal autofluorescence responses of neurons in visual cortex in a paradigm that we modified for long-term imaging in awake mice.  While wild type mice displayed normal shifts in both the spatial extent and magnitude of cortical plasticity after MD, AD mice failed to exhibit either of these changes.   These data suggest that the same genes implicated in AD may be important for plasticity earlier in life.