Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Cell Rep. 2018 Dec 11;25(11):3148-3157.e3. doi: 10.1016/j.celrep.2018.11.053.
The balance of dopamine and acetylcholine in the dorsal striatum is critical for motor and learning functions. Midbrain dopamine cells and local cholinergic interneurons (ChIs) densely innervate the striatum and have strong reciprocal actions on each other. Although dopamine inputs regulate ChIs, the functional consequences of dopamine neuron activity across dorsal striatal regions is poorly understood. Here, we find that midbrain dopamine neurons drive pauses in the firing of dorsomedial ChIs but robust bursts in dorsolateral ChIs. Pauses are mediated by dopamine D2 receptors, while bursts are driven by glutamate corelease and activation of a mGluR-mediated excitatory conductance. We find the frequency of muscarinic cholinergic transmission to medium spiny neurons is greater in the dorsomedial striatum. This regional variation in transmission is moderated by the different actions of dopamine and glutamate corelease. These results delineate a mechanism by which dopamine inputs maintain consistent levels of cholinergic activity across the dorsal striatum.
背侧纹状体中多巴胺和乙酰胆碱的平衡对于运动和学习功能至关重要。中脑多巴胺细胞和局部胆碱能中间神经元（ChIs）密集地支配纹状体，并对彼此有强烈的相互作用。尽管多巴胺输入调节 ChIs，但多巴胺神经元活动在背侧纹状体区域的功能后果知之甚少。在这里，我们发现中脑多巴胺神经元驱动背侧中间 ChIs 的暂停，但在背外侧 ChIs 中产生强烈的爆发。暂停由多巴胺 D2 受体介导，而爆发则由谷氨酸共释放和 mGluR 介导的兴奋性电导激活驱动。我们发现，中脑多巴胺神经元驱动背侧中间 ChIs 的暂停，但在背外侧 ChIs 中产生强烈的爆发。这种传递的频率在背侧纹状体中更大。这种传递的区域变化受到多巴胺和谷氨酸共释放的不同作用的调节。这些结果描绘了一种机制，通过该机制，多巴胺输入在整个背侧纹状体中维持胆碱能活动的一致水平。
