PT  - JOURNAL ARTICLE
AU  - Wesson, Daniel W.
AU  - Borkowski, Anne H.
AU  - Landreth, Gary E.
AU  - Nixon, Ralph A.
AU  - Levy, Efrat
AU  - Wilson, Donald A.
TI  - Sensory Network Dysfunction, Behavioral Impairments, and Their Reversibility in an Alzheimer's β-Amyloidosis Mouse Model
AID  - 10.1523/JNEUROSCI.2085-11.2011
DP  - 2011 Nov 02
TA  - The Journal of Neuroscience
PG  - 15962--15971
VI  - 31
IP  - 44
4099  - http://www.jneurosci.org/content/31/44/15962.short
4100  - http://www.jneurosci.org/content/31/44/15962.full
SO  - J. Neurosci.2011 Nov 02; 31
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.