Compensatory responses to age-related decline in odor quality acuity: Cholinergic neuromodulation and olfactory enrichment

NEUROBIOLOGY OF AGING

卷:32

Article

Mandairon, Nathalie^2,3,4  Peace, Shane T.^3,4  Boudadi, Karim³  Boxhorn, Christine E.³  Narla, Venkata Anupama³  Suffis, Sara D.^3,5  Cleland, Thomas A.^1,3 

[1] Cornell Univ, Dept Psychol, Ithaca, NY 14853 USA

[2] Univ Lyon 1, Lab Neurosci Sensorielles, F-69007 Lyon, France

[3] Cornell Univ, Computat Physiol Lab, Ithaca, NY 14853 USA

[4] Cornell Univ, Dept Neurobiol & Behav, Ithaca, NY 14853 USA

[5] Whitman Coll, Dept Biol, Walla Walla, WA 99362 USA

关键词: Acetylcholine;    Age-related cognitive decline;    Olfactory bulb;    Cholinergic hypothesis;    Alzheimer's disease;    Basal forebrain;    Palliative response;   

DOI  :  10.1016/j.neurobiolaging.2009.12.024

来源: Elsevier

【 摘 要 】

The perceptual differentiation of odors can be measured behaviorally using generalization gradients. The steepness of these gradients defines a form of olfactory acuity for odor quality that depends on neural circuitry within the olfactory bulb and is regulated by cholinergic activity therein as well as by associative learning. Using this system as a reduced model for age-related cognitive decline, we show that aged mice, while maintaining almost the same baseline behavioral performance as younger mice, are insensitive to the effects of acutely elevated acetylcholine, which sharpens generalization gradients in young adult mice. Moreover, older mice exhibit evidence of chronically elevated acetylcholine levels in the olfactory bulb, suggesting that their insensitivity to further elevated levels of acetylcholine may arise because the maximum capacity of the system to respond to acetylcholine has already been reached. We propose a model in which an underlying, age-related, progressive deficit is mitigated by a compensatory cholinergic feedback loop that acts to retard the behavioral effects of what would otherwise be a substantial age-related decline in olfactory plasticity. We also treated mice with 10-day regimens of olfactory environmental enrichment and/or repeated systemic injections of the acetylcholinesterase inhibitor physostigmine. Each treatment alone sharpened odor quality acuity, but administering both treatments together had no greater effect than either alone. Age was not a significant main effect in this study, suggesting that some capacity for acetylcholine-dependent plasticity is still present in aged mice despite their sharply reduced ability to respond to acute increases in acetylcholine levels. These results suggest a dynamical framework for understanding age-related decline in neural circuit processing in which the direct effects of aging can be mitigated, at least temporarily, by systemic compensatory responses. In particular, a decline in cholinergic efficacy can precede any breakdown in cholinergic production, which may help explain the limited effectiveness of cholinergic replacement therapies in combating cognitive decline. (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

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