RT Journal Article SR Electronic T1 Sensory Network Dysfunction, Behavioral Impairments, and Their Reversibility in an Alzheimer's β-Amyloidosis Mouse Model JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 15962 OP 15971 DO 10.1523/JNEUROSCI.2085-11.2011 VO 31 IS 44 A1 Daniel W. Wesson A1 Anne H. Borkowski A1 Gary E. Landreth A1 Ralph A. Nixon A1 Efrat Levy A1 Donald A. Wilson YR 2011 UL http://www.jneurosci.org/content/31/44/15962.abstract AB The unique vulnerability of the olfactory system to Alzheimer's disease (AD) provides a quintessential translational tool for understanding mechanisms of synaptic dysfunction and pathological progression in the disease. Using the Tg2576 mouse model of β-amyloidosis, we show that aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-β (Aβ) deposition is restricted to the olfactory bulb (OB). Hyperactive odor-evoked activity in the piriform cortex (PCX) and increased OB–PCX functional connectivity emerged at a time coinciding with olfactory behavior impairments. This hyperactive activity persisted until later in life when the network converted to a hyporesponsive state. This conversion was Aβ-dependent, because liver-X receptor agonist treatment to promote Aβ degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior.