Olfactory Functions Scale with Circuit Restoration in a Rapidly Reversible Alzheimer's Disease Model

• DOI: 10.1523/jneurosci.0291-13.2013
• Publication Date: 2013-07-24T22:40:58Z
• Authors: N. Cheng; L. Bai; E. Steuer; L. Belluscio
• Keywords: Biological neural network

Neural circuits maintain a precise organization that is vital for normal brain functions and behaviors, but become disrupted during neurological disease. Understanding the connection between wiring accuracy function to measure disease progression or recovery has been difficult because of complexity behavioral circuits. The olfactory system maintains well-defined neural connections regenerate throughout life. We previously established reversible in vivo model Alzheimer's by overexpressing humanized mutated amyloid precursor protein (hAPP) sensory neurons (OSNs). Using this model, we currently show hAPP present OSN axons mutant mice, which exhibit strong caspase3 signal reduced synaptic expression 3 weeks age. In bulb, glomerular structure distorted axonal convergence lost. functional imaging experiments further demonstrate disruption circuitry, assays reveal significantly impaired. Because OSNs regenerate, also tested if could recover from hAPP-induced disruption. found after 1 shutting-off expression, circuit was partially restored both anatomically functionally, with deficits similarly reversed. Interestingly, degree tracked directly restoration. Together, these data subsequent can occur rapidly behavior provide organization. Thus, olfaction may serve as useful biomarker follow gauge potential recovery.