Targeted Activation of Cholinergic Interneurons Accounts for the Modulation of Dopamine by Striatal Nicotinic Receptors.
Targeted Activation of Cholinergic Interneurons Accounts for the Modulation of Dopamine by Striatal Nicotinic Receptors.
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DOI：
10.1523/eneuro.0397-17.2018
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发表时间：
2018-09
期刊：
影响因子：
3.4
通讯作者：
Cragg SJ
中科院分区：
文献类型：
--
作者：
Brimblecombe KR;Threlfell S;Dautan D;Kosillo P;Mena-Segovia J;Cragg SJ
纹状体多巴胺（DA）是动作选择和强化的主要参与者。DA的释放受到纹状体ACh的强烈局部控制，ACh作用于DA轴突上的轴突烟碱型ACh受体（nAChRs）。纹状体nAChR已被证明控制DA如何响应于DA神经元的上升活动而释放，并且它们还在小的局部胆碱能网络中同步活动后直接驱动DA释放。纹状体乙酰胆碱的来源一直被认为是由内源性胆碱能中间神经元（ChIs）引起的，但最近的研究发现，胆碱能输入纹状体的来源是脑干核、脚桥核（PPN）和背侧被盖（LDT）。在这里，我们使用靶向光遗传学激活以及DA检测与快速扫描循环伏安法来测试是否ChIs单独和/或脑干传入纹状体可以解释ACh如何驱动和调节大鼠纹状体中的DA释放。我们证明，有针对性的短暂光激活大鼠纹状体的ChIs驱动纹状体DA释放，证实和扩展以前的观察在小鼠到大鼠。然而，同样的光刺激针对胆碱能脑干传入没有驱动DA释放，也没有调节DA释放激活随后由电刺激，而有针对性的激活ChIs这样做。我们无法获得PPN/LDT刺激对DA调节的任何证据。相比之下，我们可以很容易地确定，纹状体ChIs本身就足以提供一个ACh的来源，通过nAChRs有力地调节DA。
Striatal dopamine (DA) is a major player in action selection and reinforcement. DA release is under strong local control by striatal ACh acting at axonal nicotinic ACh receptors (nAChRs) on DA axons. Striatal nAChRs have been shown to control how DA is released in response to ascending activity from DA neurons, and they also directly drive DA release following synchronized activity in a small local cholinergic network. The source of striatal ACh has been thought to arise solely from intrinsic cholinergic interneurons (ChIs), but recent findings have identified a source of cholinergic inputs to striatum from brainstem nuclei, the pedunculopontine nucleus (PPN) and laterodorsal tegmentum (LDT). Here, we used targeted optogenetic activation alongside DA detection with fast-scan cyclic voltammetry to test whether ChIs alone and/or brainstem afferents to the striatum can account for how ACh drives and modulates DA release in rat striatum. We demonstrate that targeted transient light activation of rat striatal ChIs drives striatal DA release, corroborating and extending previous observations in mouse to rat. However, the same light stimulation targeted to cholinergic brainstem afferents did not drive DA release, and nor did it modulate DA release activated subsequently by electrical stimulation, whereas targeted activation of ChIs did so. We were unable to obtain any evidence for DA modulation by PPN/LDT stimulation. By contrast, we could readily identify that striatal ChIs alone are sufficient to provide a source of ACh that powerfully regulates DA via nAChRs.