Unique Contributions of Distinct Cholinergic Projections to Motor Cortical Plasticity and Learning
Unique Contributions of Distinct Cholinergic Projections to Motor Cortical Plasticity and Learning
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DOI：
10.1093/cercor/bhq022
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发表时间：
2010-11-01
期刊：
影响因子：
3.7
通讯作者：
Tuszynski, M. H.
中科院分区：
文献类型：
--
作者：
Conner, J. M.;Kulczycki, M.;Tuszynski, M. H.
胆碱能基底前脑投射到整个新皮质，在调节与正常学习相关的可塑性方面发挥关键作用。皮质可塑性的胆碱能调节可能来自3种不同的机制：1)通过胆碱能输入到可塑性区域的“直接”调节，2)通过胆碱能投射到前额叶注意系统的“间接”调节，或3)通过整个皮层的分布式输入来调节加工的更全局方面。为了分离这些潜在的机制，我们研究了大鼠进行熟练运动学习时皮层运动表征的胆碱能依赖性重组。我们比较了消耗运动皮质、前额皮质或整体胆碱能输入的行为和电生理后果。我们发现运动皮质胆碱能传入的局部耗竭会显著破坏脑图可塑性和熟练的运动行为，而前额叶胆碱能耗竭对这些措施没有影响。整体胆碱能耗竭对脑图可塑性的干扰与运动皮质耗竭相当，但对熟练运动习得的损害明显更大。这些研究结果表明，运动皮层的局部胆碱能激活，而不是前额叶系统的间接调节，调节皮层地图可塑性和运动学习。更全面的胆碱能机制为熟练的运动行为的获得提供了额外的支持，而不仅仅是那些与皮层图谱重组相关的机制。
The cholinergic basal forebrain projects throughout the neocortex, exerting a critical role in modulating plasticity associated with normal learning. Cholinergic modulation of cortical plasticity could arise from 3 distinct mechanisms by 1) "direct" modulation via cholinergic inputs to regions undergoing plasticity, 2) "indirect" modulation via cholinergic projections to anterior, prefrontal attentional systems, or 3) modulating more global aspects of processing via distributed inputs throughout the cortex. To segregate these potential mechanisms, we investigated cholinergic-dependent reorganization of cortical motor representations in rats undergoing skilled motor learning. Behavioral and electrophysiological consequences of depleting cholinergic inputs to either motor cortex, prefrontal cortex, or globally, were compared. We find that local depletion of cholinergic afferents to motor cortex significantly disrupts map plasticity and skilled motor behavior, whereas prefrontal cholinergic depletion has no effect on these measures. Global cholinergic depletion perturbs map plasticity comparable with motor cortex depletions but results in significantly greater impairments in skilled motor acquisition. These findings indicate that local cholinergic activation within motor cortex, as opposed to indirect regulation of prefrontal systems, modulate cortical map plasticity and motor learning. More globally acting cholinergic mechanisms provide additional support for the acquisition of skilled motor behaviors, beyond those associated with cortical map reorganization.