| First Author | Wesson DW | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 44 | Pages | 15962-71 |
| PubMed ID | 22049439 | Mgi Jnum | J:177844 |
| Mgi Id | MGI:5296395 | Doi | 10.1523/JNEUROSCI.2085-11.2011 |
| Citation | Wesson DW, et al. (2011) Sensory Network Dysfunction, Behavioral Impairments, and Their Reversibility in an Alzheimer's beta-Amyloidosis Mouse Model. J Neurosci 31(44):15962-15971 |
| abstractText | 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 beta-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-beta (Abeta) 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 Abeta-dependent, because liver-X receptor agonist treatment to promote Abeta 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. |
