Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
Neurobiol Aging. 2012 Aug;33(8):1744-57. doi: 10.1016/j.neurobiolaging.2011.03.020. Epub 2011 Apr 30.
Cognitive flexibility is critical for survival and reflects the malleability of the central nervous system (CNS) in response to changing environmental demands. Normal aging results in difficulties modifying established behaviors, which may involve medial prefrontal cortex (mPFC) dysfunction. Using extinction of conditioned fear in rats to assay cognitive flexibility, we demonstrate that extinction deficits reminiscent of mPFC dysfunction first appear during middle age, in the absence of hippocampus-dependent context deficits. Emergence of aging-related extinction deficits paralleled a redistribution of neuronal excitability across two critical mPFC regions via two distinct mechanisms. First, excitability decreased in regular spiking neurons of infralimbic-mPFC (IL), a region whose activity is required for extinction. Second, excitability increased in burst spiking neurons of prelimbic-mPFC (PL), a region whose activity hinders extinction. Experiments using synaptic blockers revealed that these aging-related differences were intrinsic. Thus, changes in IL and PL intrinsic excitability may contribute to cognitive flexibility impairments observed during normal aging.
认知灵活性对于生存至关重要，反映了中枢神经系统（CNS）对不断变化的环境需求的可塑性。正常衰老会导致难以改变既定的行为，这可能涉及内侧前额叶皮层（mPFC）功能障碍。我们使用大鼠条件性恐惧的消除来测定认知灵活性，结果表明，类似于 mPFC 功能障碍的消除缺陷首先出现在中年，而没有海马依赖性的上下文缺陷。与年龄相关的消除缺陷的出现与通过两种不同的机制在两个关键的 mPFC 区域中跨神经元兴奋性的重新分布平行。首先，IL 中的规则放电神经元的兴奋性降低，IL 是进行消除所必需的区域。其次，PL 中的爆发放电神经元的兴奋性增加，PL 是抑制消除的区域。使用突触阻滞剂的实验表明，这些与年龄相关的差异是内在的。因此，IL 和 PL 内在兴奋性的变化可能导致正常衰老过程中观察到的认知灵活性受损。
