Sympathetic sprouting in visual cortex stimulated by cholinergic denervation rescues expression of two forms of long-term depression at layer 2/3 synapses.
Sympathetic sprouting in visual cortex stimulated by cholinergic denervation rescues expression of two forms of long-term depression at layer 2/3 synapses.
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DOI：
10.1016/j.neuroscience.2010.04.027
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发表时间：
2010-07-14
期刊：
影响因子：
3.3
通讯作者：
McMahon, L. L.
中科院分区：
文献类型：
--
作者：
McCoy, P. A.;McMahon, L. L.
海马和皮层的胆碱能神经支配是某些形式的学习和记忆所必需的。一些报告表明，激活毒蕈碱m1受体诱导海马和几个皮层区域（包括嗅周和视觉皮层）的谷氨酸突触的长期抑制（mLTD）。这种可塑性可能有助于依赖于胆碱能系统的认知功能。在啮齿动物模型中，内侧隔损伤后海马胆碱能神经支配的退化刺激源自上级颈神经节（SCG）的肾上腺素能交感神经轴突发芽进入失神经支配的海马亚区。我们以前报道过，这种肾上腺素能交感神经发芽同时发生的海马和救援的mLTD在CA 3-CA 1突触的胆碱能纤维的再现。由于整个基底前脑的胆碱能神经元在衰老和阿尔茨海默病中退化，因此确定这种补偿性发芽是否发生在受胆碱能细胞损失影响的其他区域至关重要。为此，我们研究是否基底核大细胞（NbM）胆碱能去神经皮质的病变刺激肾上腺素能交感神经萌芽和伴随的胆碱能神经支配的增加。此外，我们评估了发芽的存在是否与急性视皮层切片中谷氨酸突触表达mLTD和低频刺激诱导的LTD（LFS LTD）（视皮层中另一种胆碱能依赖形式的可塑性）的能力呈正相关。我们发现，当NbM损伤与双侧SCG切除相结合以防止可能的代偿性发芽时，mLTD和LFS LTD在动物中均不存在。相比之下，当SCG保持完整，允许发芽的动物与NbM病变，胆碱能纤维密度增加，同时肾上腺素能交感神经发芽，和mLTD和LFS LTD被保存。我们的研究结果表明，中枢胆碱能变性的自主代偿不是海马所特有的，而是发生在对正常认知功能重要的其他脑区的一般修复机制。
Cholinergic innervation of hippocampus and cortex is required for some forms of learning and memory. Several reports have shown that activation of muscarinic m1 receptors induces a long-term depression (mLTD) at glutamate synapses in hippocampus and in several areas of cortex, including perirhinal and visual cortices. This plasticity likely contributes to cognitive function dependent upon the cholinergic system. In rodent models, degeneration of hippocampal cholinergic innervation following lesion of the medial septum stimulates sprouting of adrenergic sympathetic axons, originating from the superior cervical ganglia (SCG), into denervated hippocampal subfields. We previously reported that this adrenergic sympathetic sprouting occurs simultaneously with a reappearance of cholinergic fibers in hippocampus and rescue of mLTD at CA3-CA1 synapses. Because cholinergic neurons throughout basal forebrain degenerate in aging and Alzheimer's disease, it is critical to determine if this compensatory sprouting occurs in other regions impacted by cholinergic cell loss. To this end, we investigated whether lesion of the nucleus basalis magnocellularis (NbM) to cholinergically denervate cortex stimulates adrenergic sympathetic sprouting and the accompanying increase in cholinergic innervation. Further, we assessed whether the presence of sprouting positively correlates with the ability of glutamate synapses in acute visual cortex slices to express mLTD and low frequency stimulation induced LTD (LFS LTD), another cholinergic dependent form of plasticity in visual cortex. We found that both mLTD and LFS LTD are absent in animals when NbM lesion is combined with bilateral removal of the SCG to prevent possible compensatory sprouting. In contrast, when the SCG remain intact to permit sprouting in animals with NbM lesion, cholinergic fiber density is increased concurrently with adrenergic sympathetic sprouting, and mLTD and LFS LTD are preserved. Our findings suggest that autonomic compensation for central cholinergic degeneration is not specific to hippocampus, but is a general repair mechanism occurring in other brain regions important for normal cognitive function.
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