Activity Patterns in the Neuropil of Striatal Cholinergic Interneurons in Freely Moving Mice Represent Their Collective Spiking Dynamics
Activity Patterns in the Neuropil of Striatal Cholinergic Interneurons in Freely Moving Mice Represent Their Collective Spiking Dynamics
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DOI：
10.1523/eneuro.0351-18.2018
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发表时间：
2019-01-01
期刊：
影响因子：
3.4
通讯作者：
Goldberg, Joshua A.
中科院分区：
文献类型：
--
作者：
Rehani, Rotem;Atamna, Yara;Goldberg, Joshua A.
胆碱能中间神经元（CINs）被认为形成同步细胞组装，调节纹状体微电路并可能协调局部多巴胺释放。我们表达GCaMP 6s，一种遗传编码的钙指示剂（GECIs），选择性地在CIN中，并使用显微内窥镜观察自由活动小鼠背侧纹状体中假定的CIN组件。来自背侧纹状体的GECI荧光信号由来自被广泛的荧光神经元吞噬的单个CIN胞体的信号组成。发作的胆碱能神经元的同步激活显示的活动模式之前的信号从个别的胞体。为了研究神经元信号的性质以及为什么它先于躯体信号，我们结合模拟显微内窥镜规格的多光子成像或宽视场成像，在急性纹状体切片中靶向修补表达GECI的CIN。检测与个体动作电位相关的荧光瞬变的能力受到GECIs（相对于常见无机染料）的长衰减常数的限制，以缓慢激发（< 2尖峰/s）CINS。显微内窥镜的分辨率和采样率进一步削弱了这种能力。此外，我们发现，只有反向传播的动作电位，而不是同步光遗传激活丘脑输入引起可观察到的钙瞬变CIN树突。我们的数据表明，只有爆发的CIN活动（但不是他们的紧张性放电）是可见的使用内窥镜成像，神经元放电模式是一个生理措施的集体复发CIN网络尖峰活动。
Cholinergic interneurons (CINs) are believed to form synchronous cell assemblies that modulate the striatal microcircuitry and possibly orchestrate local dopamine release. We expressed GCaMP6s, a genetically encoded calcium indicator (GECIs), selectively in CINs, and used microendoscopes to visualize the putative CIN assemblies in the dorsal striatum of freely moving mice. The GECI fluorescence signal from the dorsal striatum was composed of signals from individual CIN somata that were engulfed by a widespread fluorescent neuropil. Bouts of synchronous activation of the cholinergic neuropil revealed patterns of activity that preceded the signal from individual somata. To investigate the nature of the neuropil signal and why it precedes the somatic signal, we target-patched GECI-expressing CINs in acute striatal slices in conjunction with multiphoton imaging or wide-field imaging that emulates the microendoscopes' specifications. The ability to detect fluorescent transients associated with individual action potential was constrained by the long decay constant of GECIs (relative to common inorganic dyes) to slowly firing (< 2 spikes/s) CINs. The microendoscopes' resolving power and sampling rate further diminished this ability. Additionally, we found that only back-propagating action potentials but not synchronous optogenetic activation of thalamic inputs elicited observable calcium transients in CIN dendrites. Our data suggest that only bursts of CIN activity (but not their tonic firing) are visible using endoscopic imaging, and that the neuropil patterns are a physiological measure of the collective recurrent CIN network spiking activity.