Linking cell types to behavior in the vertebrate hypothalamus.
Linking cell types to behavior in the vertebrate hypothalamus.
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将细胞类型与脊椎动物下丘脑的行为联系起来。
DOI：
10.1038/s41386-020-00845-y
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Lovett-Barron,Matthew
中科院分区：
文献类型：
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作者：
Lovett-Barron,Matthew
神经元可以根据各种不同的属性进行分类，包括它们的解剖学，遗传学，连接性或活动。然而，目前还不清楚这些不同的分类如何相互关联[1]，特别是在脊椎动物下丘脑等大脑区域，在那里测量相同神经元的分子身份和活动模式是具有挑战性的。最近的两项研究已经克服了小鼠的这些挑战，使用单细胞RNA测序来联合测量神经元的分子身份和特定行为经历后活性依赖性基因的表达[2，3]。Moffitt等人[2]使用空间转录组学对下丘脑内侧视前区的神经元进行分类，并得出结论，不同的社会行为招募不同的神经元分子亚类。使用互补的方法，Kim et al. [3]分析了下丘脑腹内侧的基因表达和轴突投射，但发现在社会行为后表达活动依赖基因的神经元包括许多分子和投射定义的亚类细胞。尽管从这些研究中获得了大量的见解，但神经元的快速时间尺度活动模式并没有被活动依赖性基因表达捕获，从而阻碍了基于其活动的神经元的详细表征。为了联合测量同一神经元中多个基因的快速时间尺度活动和表达，我们开发了一种方法，将活脑钙成像和固定脑多路复用基因表达标记合并，以单细胞分辨率在大群体中进行[4，5]。我们将其应用于斑马鱼幼虫的下丘脑;与哺乳动物一样，鱼类下丘脑由保守的肽能细胞类型组成，并指导多种先天行为，但在行为期间可用于非侵入性神经活动成像[6]。我们记录了斑马鱼室旁下丘脑同源物中表达神经肽的细胞类型，我们观察到不同的威胁（突然增加的热量，酸度或盐度）会招募不同的神经群体[5]。为了确定功能反应的差异是否对应于神经肽表达的差异，我们同时对神经元的活动进行了成像，
Neurons can be categorized according to a variety of different attributes, including their anatomy, genetics, connectivity, or activity. However, it is unclear how these different categorizations relate to one another [1], especially in brain regions like the vertebrate hypothalamus, where it is challenging to measure the molecular identity and activity patterns of the same neurons. Two recent studies have overcome these challenges in mice, using single-cell RNA-sequencing to jointly measure the molecular identity of neurons and the expression of activity-dependent genes after specific behavioral experiences [2, 3]. Moffitt et al.[2] used spatial transcriptomics to classify neurons in the medial preoptic region of the hypothalamus, and concluded that different social behaviors recruit different molecular subclasses of neurons. Using a complementary approach, Kim et al.[3] analyzed gene expression and axonal projections in the ventromedial hypothalamus, but found that neurons expressing activity-dependent genes after social behaviors included cells of many molecular and projection-defined subclasses. Despite the substantial insights gained from these studies, the fast-timescale activity patterns of neurons are not captured by activity-dependent gene expression, preventing detailed characterization of neurons based on their activity.To jointly measure the fast-timescale activity and expression of multiple genes in the same neurons, we developed a method to merge live-brain calcium imaging and fixed-brain multiplexed gene expression labeling, across large populations at single-cell resolution [4, 5]. We applied this to the hypothalamus of larval zebrafish; like mammals, the fish hypothalamus is composed of conserved peptidergic cell types and directs multiple innate behaviors, but is accessible for non-invasive neural activity imaging during behavior [6]. We recorded from neuropeptideexpressing cell types in the zebrafish homolog of the paraventricular hypothalamus, where we had observed that different threats (sudden increases in heat, acidity, or salinity) would recruit different neural populations [5]. To determine if differences in functional responses corresponded to differences in neuropeptide expression, we simultaneously imaged the activity of neurons that