Suppr超能文献

Cre-Lox转基因小鼠胆碱能神经元中通道视紫红质和古菌视紫红质的特性研究

Characterization of Channelrhodopsin and Archaerhodopsin in Cholinergic Neurons of Cre-Lox Transgenic Mice.

作者信息

Hedrick Tristan, Danskin Bethanny, Larsen Rylan S, Ollerenshaw Doug, Groblewski Peter, Valley Matthew, Olsen Shawn, Waters Jack

机构信息

Northwestern University, 303 E Chicago Ave, Chicago IL 60611, United States of America.

Allen Institute for Brain Science, 551 N 34th St, Seattle WA 98103, United States of America.

出版信息

PLoS One. 2016 May 31;11(5):e0156596. doi: 10.1371/journal.pone.0156596. eCollection 2016.

Abstract

The study of cholinergic signaling in the mammalian CNS has been greatly facilitated by the advent of mouse lines that permit the expression of reporter proteins, such as opsins, in cholinergic neurons. However, the expression of opsins could potentially perturb the physiology of opsin-expressing cholinergic neurons or mouse behavior. Indeed, the published literature includes examples of cellular and behavioral perturbations in preparations designed to drive expression of opsins in cholinergic neurons. Here we investigate expression of opsins, cellular physiology of cholinergic neurons and behavior in two mouse lines, in which channelrhodopsin-2 (ChR2) and archaerhodopsin (Arch) are expressed in cholinergic neurons using the Cre-lox system. The two mouse lines were generated by crossing ChAT-Cre mice with Cre-dependent reporter lines Ai32(ChR2-YFP) and Ai35(Arch-GFP). In most mice from these crosses, we observed expression of ChR2 and Arch in only cholinergic neurons in the basal forebrain and in other putative cholinergic neurons in the forebrain. In small numbers of mice, off-target expression occurred, in which fluorescence did not appear limited to cholinergic neurons. Whole-cell recordings from fluorescently-labeled basal forebrain neurons revealed that both proteins were functional, driving depolarization (ChR2) or hyperpolarization (Arch) upon illumination, with little effect on passive membrane properties, spiking pattern or spike waveform. Finally, performance on a behavioral discrimination task was comparable to that of wild-type mice. Our results indicate that ChAT-Cre x reporter line crosses provide a simple, effective resource for driving indicator and opsin expression in cholinergic neurons with few adverse consequences and are therefore an valuable resource for studying the cholinergic system.

摘要

允许在胆碱能神经元中表达报告蛋白(如视蛋白)的小鼠品系的出现,极大地促进了对哺乳动物中枢神经系统中胆碱能信号传导的研究。然而,视蛋白的表达可能会干扰表达视蛋白的胆碱能神经元的生理学或小鼠行为。事实上,已发表的文献中有一些例子,展示了在旨在驱动胆碱能神经元中视蛋白表达的实验准备中出现的细胞和行为扰动。在这里,我们研究了两种小鼠品系中视蛋白的表达、胆碱能神经元的细胞生理学和行为,在这两种小鼠品系中,使用Cre-lox系统在胆碱能神经元中表达了通道视紫红质-2(ChR2)和古紫质(Arch)。这两种小鼠品系是通过将ChAT-Cre小鼠与依赖Cre的报告品系Ai32(ChR2-YFP)和Ai35(Arch-GFP)杂交产生的。在这些杂交产生的大多数小鼠中,我们仅在前脑基底的胆碱能神经元和前脑其他假定的胆碱能神经元中观察到ChR2和Arch的表达。在少数小鼠中,出现了非靶向表达,荧光并不局限于胆碱能神经元。对荧光标记的前脑基底神经元进行的全细胞记录显示,这两种蛋白都具有功能,光照时可驱动去极化(ChR2)或超极化(Arch),对被动膜特性、放电模式或动作电位波形影响很小。最后,在行为辨别任务中的表现与野生型小鼠相当。我们的结果表明,ChAT-Cre×报告品系杂交为在胆碱能神经元中驱动指示剂和视蛋白表达提供了一种简单、有效的资源,不良后果很少,因此是研究胆碱能系统的宝贵资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f09/4886964/f0c5f28ced86/pone.0156596.g001.jpg

相似文献

1
Characterization of Channelrhodopsin and Archaerhodopsin in Cholinergic Neurons of Cre-Lox Transgenic Mice.
PLoS One. 2016 May 31;11(5):e0156596. doi: 10.1371/journal.pone.0156596. eCollection 2016.
4
Leaky expression of channelrhodopsin-2 (ChR2) in Ai32 mouse lines.
PLoS One. 2019 Mar 26;14(3):e0213326. doi: 10.1371/journal.pone.0213326. eCollection 2019.
6
Generation of a ChAT mouse line without the early onset hearing loss typical of the C57BL/6J strain.
Hear Res. 2020 Mar 15;388:107896. doi: 10.1016/j.heares.2020.107896. Epub 2020 Jan 20.
9
Topographic mapping between basal forebrain cholinergic neurons and the medial prefrontal cortex in mice.
J Neurosci. 2014 Dec 3;34(49):16234-46. doi: 10.1523/JNEUROSCI.3011-14.2014.
10
Fast modulation of visual perception by basal forebrain cholinergic neurons.
Nat Neurosci. 2013 Dec;16(12):1857-1863. doi: 10.1038/nn.3552. Epub 2013 Oct 27.

引用本文的文献

2
Reward contingency gates selective cholinergic suppression of amygdala neurons.
Elife. 2024 Feb 20;12:RP89093. doi: 10.7554/eLife.89093.
3
Light-Driven Sodium Pump as a Potential Tool for the Control of Seizures in Epilepsy.
Mol Neurobiol. 2024 Jul;61(7):4691-4704. doi: 10.1007/s12035-023-03865-z. Epub 2023 Dec 20.
4
Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation.
Nat Biomed Eng. 2024 Jul;8(7):808-822. doi: 10.1038/s41551-023-01113-2. Epub 2023 Nov 9.
5
Differential Regulation of Prelimbic and Thalamic Transmission to the Basolateral Amygdala by Acetylcholine Receptors.
J Neurosci. 2023 Feb 1;43(5):722-735. doi: 10.1523/JNEUROSCI.2545-21.2022. Epub 2022 Dec 19.
6
Modeling optical design parameters for fine stimulation in sciatic nerve of optogenetic mice.
Sci Rep. 2021 Nov 19;11(1):22588. doi: 10.1038/s41598-021-01353-9.
7
Alteration of the cholinergic system and motor deficits in cholinergic neuron-specific Dyt1 knockout mice.
Neurobiol Dis. 2021 Jul;154:105342. doi: 10.1016/j.nbd.2021.105342. Epub 2021 Mar 20.

本文引用的文献

1
Nicotinic Transmission onto Layer 6 Cortical Neurons Relies on Synaptic Activation of Non-α7 Receptors.
Cereb Cortex. 2016 Jun;26(6):2549-2562. doi: 10.1093/cercor/bhv085. Epub 2015 May 1.
2
Corelease of acetylcholine and GABA from cholinergic forebrain neurons.
Elife. 2015 Feb 27;4:e06412. doi: 10.7554/eLife.06412.
3
Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors.
J Neurophysiol. 2015 Apr 1;113(7):2195-209. doi: 10.1152/jn.00716.2014. Epub 2015 Jan 14.
4
Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors.
Front Synaptic Neurosci. 2014 Oct 27;6:24. doi: 10.3389/fnsyn.2014.00024. eCollection 2014.
5
Fast modulation of visual perception by basal forebrain cholinergic neurons.
Nat Neurosci. 2013 Dec;16(12):1857-1863. doi: 10.1038/nn.3552. Epub 2013 Oct 27.
7
Ultrasensitive fluorescent proteins for imaging neuronal activity.
Nature. 2013 Jul 18;499(7458):295-300. doi: 10.1038/nature12354.
10
Selective optogenetic stimulation of cholinergic axons in neocortex.
J Neurophysiol. 2012 Apr;107(7):2008-19. doi: 10.1152/jn.00870.2011. Epub 2012 Jan 11.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验