Novel fast adapting interneurons mediate cholinergic-induced fast GABAA inhibitory postsynaptic currents in striatal spiny neurons.
Novel fast adapting interneurons mediate cholinergic-induced fast GABAA inhibitory postsynaptic currents in striatal spiny neurons.
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DOI：
10.1111/ejn.12915
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Koós T
中科院分区：
文献类型：
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作者：
Faust TW;Assous M;Shah F;Tepper JM;Koós T
先前的研究表明，新纹状体胆碱能中间神经元通过快速烟碱受体介导的突触输入控制几类GABA能中间神经元的活动。虽然间接证据表明存在几类由这种机制控制的中间神经元，但迄今为止仅鉴定出一种这样的细胞类型，即表达神经肽Y的神经胶质样神经元。在这里，我们测试的假设，除了引起缓慢的GABA能抑制反应的神经胶质样神经元，另一种类型的中间神经元存在于纹状体，接受强烟碱胆碱能输入和eleranized传统的快速GABA能突触反应的投射神经元。我们从双转基因小鼠中获得了体外切片记录，在双转基因小鼠中，视紫红质-2在胆碱能神经元中天然表达，并且用tdTomato可视化了5-羟色胺受体-3a-Cre表达GABA能中间神经元的群体。我们发现，在目标GABA能中间神经元的一种新类型的中间神经元，称为快速适应的中间神经元，可以确定是不同于以前已知的中间神经元的免疫细胞化学和电生理标准。我们使用胆碱能输入的光遗传学激活表明，快速适应的中间神经元在体外接受强大的阈上烟碱胆碱能输入。此外，快速适应神经元与投射神经元紧密相连，并引起快速的GABAA受体介导的抑制性突触后反应。烟碱受体介导的快速适应性中间神经元的激活可能构成了一个重要的机制，通过该机制，胆碱能中间神经元控制投射神经元的活性，并可能在动物遇到强化或其他突出刺激时控制其突触输入的可塑性。
Previous work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism only one such cell type, the neuropeptide-Y expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that elicit slow GABAergic inhibitory responses, another interneuron type exists in the striatum that receives strong nicotinic cholinergic input and elicits conventional fast GABAergic synaptic responses in projection neurons. We obtained in vitro slice recordings from double transgenic mice in which Channelrhodopsin-2 was natively expressed in cholinergic neurons and a population of serotonin receptor-3a-Cre expressing GABAergic interneurons were visualized with tdTomato. We show that among the targeted GABAergic interneurons a novel type of interneuron, termed the fast-adapting interneuron, can be identified that is distinct from previously known interneurons based on immunocytochemical and electrophysiological criteria. We show using optogenetic activation of cholinergic inputs that fast-adapting interneurons receive a powerful supra-threshold nicotinic cholinergic input in vitro. Moreover, fast adapting neurons are densely connected to projection neurons and elicit fast, GABAA receptor mediated inhibitory postsynaptic responses. The nicotinic receptor mediated activation of fast-adapting interneurons may constitute an important mechanism through which cholinergic interneurons control the activity of projection neurons and perhaps the plasticity of their synaptic inputs when animals encounter reinforcing or otherwise salient stimuli.