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使用 Syt6-Cre 转基因小鼠对联合皮层的皮质丘脑神经元进行特征描述和操作。

Characterization and manipulation of Corticothalamic neurons in associative cortices using Syt6-Cre transgenic mice.

机构信息

Neuroscience Program, Tulane Brain Institute, Tulane University, New Orleans, Louisiana, USA.

Department of Cell and Molecular Biology and Tulane Brain Institute, Tulane University, New Orleans, Louisiana, USA.

出版信息

J Comp Neurol. 2022 May;530(7):1020-1048. doi: 10.1002/cne.25256. Epub 2021 Oct 23.

DOI:10.1002/cne.25256
PMID:34617601
Abstract

Corticothalamic interactions between associative cortices and higher order thalamic nuclei are involved in high-cognitive functions such as decision-making and working memory. Corticothalamic neurons (CTn) in the prefrontal cortex and other associative areas have been much less studied than their counterparts in the primary sensory areas. The availability of characterized transgenic tools to study CTn in associative areas will facilitate their study and contribute to overcome the scarcity of data about their properties, network dynamics, and contribution to cognitive functions. Here, we characterized the Syt6-Cre (KI148Gsat/Mmud) transgenic mouse line, by tracking expression of a Cre-mediated reporter. In this line, Cre-reporter is strongly expressed in the prefrontal, motor, cingulate, and retrosplenial cortices, as well as in other brain areas including the cerebellum and the olfactory tubercle. Cortical expression starts embryonically and reaches the adult expression pattern by postnatal day 15. In the cortex, Cre-reporter is expressed by layer 6-CTn and by layer 5-CTn to a lesser extent. We quantified Syt6-Cre CTn axon varicosities to estimate the distribution and density of putative corticothalamic driver and modulator inputs to thalamic nuclei in the medial, midline, intralaminar, anterior, and motor groups. Also, we characterized the effect of optogenetic stimulation of Syt6-Cre neurons in the activity of the prefrontal cortex. CTn stimulation in the prefrontal cortex induces an oscillatory activity in the local field potential that resembles the cortical downstates typically observed during slow-wave sleep or quiet wake.

摘要

联合皮质与高级丘脑核之间的皮质丘脑相互作用参与了高认知功能,如决策和工作记忆。与初级感觉区域相比,前额叶皮层和其他联合区域的皮质丘脑神经元(CTn)的研究要少得多。具有特征性的转基因工具可用于研究联合区域中的 CTn,这将有助于对其进行研究,并有助于克服有关其特性、网络动力学及其对认知功能的贡献的数据稀缺问题。在这里,我们通过跟踪 Cre 介导的报告基因的表达,对 Syt6-Cre(KI148Gsat/Mmud)转基因小鼠品系进行了表征。在该品系中,Cre-报告基因在额皮质、运动皮质、扣带皮质和后扣带回皮质以及包括小脑和嗅结节在内的其他脑区中强烈表达。皮层表达始于胚胎期,并在出生后第 15 天达到成年表达模式。在皮层中,Cre-报告基因由第 6 层-CTn 和第 5 层-CTn 表达,程度较小。我们量化了 Syt6-Cre CTn 轴突末梢,以估计内侧、中线、层间、前核和运动核中潜在的皮质丘脑驱动和调制输入的分布和密度。此外,我们还描述了 Syt6-Cre 神经元的光遗传学刺激对前额叶皮层活动的影响。前额叶皮层中的 CTn 刺激会在前额叶皮层局部场电位中诱导出一种类似于慢波睡眠或安静清醒期间通常观察到的皮质下状态的振荡活动。

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