Department of Neurosciences, University of California-San Diego, La Jolla, CA 92093-0626, USA.
Cereb Cortex. 2010 Nov;20(11):2739-48. doi: 10.1093/cercor/bhq022. Epub 2010 Feb 24.
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.
胆碱能基底前脑投射到整个新皮层，在调节与正常学习相关的可塑性方面发挥着关键作用。 皮层可塑性的胆碱能调制可能源于 3 种不同的机制：1）通过向经历可塑性的区域的胆碱能输入进行“直接”调制，2）通过胆碱能投射到前额叶注意力系统进行“间接”调制，或 3）通过在整个皮层中的分布式输入来调节更全局的处理方面。 为了分离这些潜在的机制，我们研究了在进行熟练运动学习的大鼠中，胆碱能依赖性的皮层运动代表区的重组。 比较了耗尽运动皮层、前额叶皮层或全局胆碱能输入对行为和电生理后果的影响。 我们发现，运动皮层胆碱能传入的局部耗竭显着破坏了图谱可塑性和熟练运动行为，而前额叶胆碱能耗竭对这些措施没有影响。 全局胆碱能耗竭使图谱可塑性与运动皮层耗竭相当，但在熟练运动获得方面的损伤明显更大。 这些发现表明，与调节前额叶系统的间接调节相反，运动皮层内的局部胆碱能激活调节皮层图谱可塑性和运动学习。 更具全局作用的胆碱能机制为获得熟练的运动行为提供了额外的支持，而不仅仅是与皮层图谱重组相关的行为。
