Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation.
Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation.
复制标题
DOI：
10.1016/j.neuron.2018.04.027
复制
发表时间：
2018-06-06
期刊：
影响因子：
16.2
通讯作者：
Cragg SJ
中科院分区：
文献类型：
--
作者：
Zhang YF;Reynolds JNJ;Cragg SJ
纹状体的胆碱能中间神经元（ChIs）在学习后暂停放电以响应显着刺激和条件刺激。已经提出了几种不同的暂停生成机制，但之前尚未出现统一的基础。在这里，利用大鼠和小鼠大脑的体内和离体记录以及计算模型，我们表明 ChI 暂停是由纹状体兴奋性输入的撤回驱动的，并且是延迟整流钾电流 (IKr) 与局部神经调节相结合的结果。 IKr 对 Kv7.2/7.3 阻断剂 XE-991 敏感，使 ChIs 能够报告输入变化、在兴奋性输入衰退时暂停，并根据输入强度调整暂停，以与学习期间的暂停获取保持一致。我们还表明，虽然多巴胺可以直接使 ChI 超极化，但其停顿的增加最好通过加强兴奋性输入来解释。这些发现为理解纹状体 ChI 中暂停的产生提供了基础。纹状体兴奋性输入的撤回会导致 ChIs 暂停 Kv7 介导的钾电流 (IKr) 延迟整流是暂停的基础 突触加权而不是多巴胺直接超极化促进暂停 ChIs 比纹状体投射神经元更快地响应兴奋性输入揭示了纹状体胆碱能中间神经元中的同步暂停反应是如何通过延迟整流电流对兴奋性输入撤回的响应来驱动的，并结合多巴胺来增强学习过程中的暂停。
Cholinergic interneurons (ChIs) of the striatum pause their firing in response to salient stimuli and conditioned stimuli after learning. Several different mechanisms for pause generation have been proposed, but a unifying basis has not previously emerged. Here, using in vivo and ex vivo recordings in rat and mouse brain and a computational model, we show that ChI pauses are driven by withdrawal of excitatory inputs to striatum and result from a delayed rectifier potassium current (IKr) in concert with local neuromodulation. The IKr is sensitive to Kv7.2/7.3 blocker XE-991 and enables ChIs to report changes in input, to pause on excitatory input recession, and to scale pauses with input strength, in keeping with pause acquisition during learning. We also show that although dopamine can hyperpolarize ChIs directly, its augmentation of pauses is best explained by strengthening excitatory inputs. These findings provide a basis to understand pause generation in striatal ChIs. Withdrawal of excitatory input to striatum induces pauses in ChIs Delayed rectification by a Kv7-mediated potassium current (IKr) underlies pauses Synapse weighting rather than direct hyperpolarization by dopamine promotes pauses ChIs are faster to respond to excitatory input than striatal projection neurons Zhang et al. reveal how synchronized pause responses in striatal cholinergic interneurons are driven, through the response of a delayed rectifier current to withdrawal of excitatory inputs, in conjunction with dopamine acting to potentiate the pause during learning.
登录
查看更多内容
影响因子：
5.3
作者：
Mallet, N;Ballion, B;Gonon, F
通讯作者：
Gonon, F
影响因子：
2
作者：
Apicella, P;Legallet, E;Trouche, E
通讯作者：
Trouche, E
DOI：
10.1073/pnas.81.15.4998
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KIMURA, M;RAJKOWSKI, J;EVARTS, E
通讯作者：
EVARTS, E
影响因子：
5.3
作者：
Bennett, BD;Callaway, JC;Wilson, CJ
通讯作者：
Wilson, CJ
影响因子：
4.1
作者：
Halliday, Glenda M.
通讯作者：
Halliday, Glenda M.