Geerling Joel C, Kim Minjee, Mahoney Carrie E, Abbott Stephen B G, Agostinelli Lindsay J, Garfield Alastair S, Krashes Michael J, Lowell Bradford B, Scammell Thomas E
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland;
Am J Physiol Regul Integr Comp Physiol. 2016 Jan 1;310(1):R41-54. doi: 10.1152/ajpregu.00094.2015. Epub 2015 Oct 21.
The parabrachial nucleus is important for thermoregulation because it relays skin temperature information from the spinal cord to the hypothalamus. Prior work in rats localized thermosensory relay neurons to its lateral subdivision (LPB), but the genetic and neurochemical identity of these neurons remains unknown. To determine the identity of LPB thermosensory neurons, we exposed mice to a warm (36°C) or cool (4°C) ambient temperature. Each condition activated neurons in distinct LPB subregions that receive input from the spinal cord. Most c-Fos+ neurons in these LPB subregions expressed the transcription factor marker FoxP2. Consistent with prior evidence that LPB thermosensory relay neurons are glutamatergic, all FoxP2+ neurons in these subregions colocalized with green fluorescent protein (GFP) in reporter mice for Vglut2, but not for Vgat. Prodynorphin (Pdyn)-expressing neurons were identified using a GFP reporter mouse and formed a caudal subset of LPB FoxP2+ neurons, primarily in the dorsal lateral subnucleus (PBdL). Warm exposure activated many FoxP2+ neurons within PBdL. Half of the c-Fos+ neurons in PBdL were Pdyn+, and most of these project into the preoptic area. Cool exposure activated a separate FoxP2+ cluster of neurons in the far-rostral LPB, which we named the rostral-to-external lateral subnucleus (PBreL). These findings improve our understanding of LPB organization and reveal that Pdyn-IRES-Cre mice provide genetic access to warm-activated, FoxP2+ glutamatergic neurons in PBdL, many of which project to the hypothalamus.
臂旁核对于体温调节很重要,因为它将来自脊髓的皮肤温度信息传递至下丘脑。此前在大鼠身上开展的研究将温度感觉中继神经元定位到其外侧亚区(LPB),但这些神经元的基因和神经化学特征仍不清楚。为了确定LPB温度感觉神经元的特征,我们将小鼠暴露于温暖(36°C)或凉爽(4°C)的环境温度下。每种条件都激活了LPB中不同亚区的神经元,这些亚区接收来自脊髓的输入。这些LPB亚区中的大多数c-Fos+神经元表达转录因子标记物FoxP2。与先前关于LPB温度感觉中继神经元是谷氨酸能神经元的证据一致,这些亚区中所有FoxP2+神经元在Vglut2报告基因小鼠中与绿色荧光蛋白(GFP)共定位,但在Vgat报告基因小鼠中则不然。使用GFP报告基因小鼠鉴定出表达强啡肽原(Pdyn)的神经元,它们构成了LPB FoxP2+神经元的尾侧亚群,主要位于背外侧亚核(PBdL)。温暖环境暴露激活了PBdL内许多FoxP2+神经元。PBdL中一半的c-Fos+神经元是Pdyn+,其中大多数投射到视前区。凉爽环境暴露激活了LPB最前端一个单独的FoxP2+神经元簇,我们将其命名为嘴侧至外侧亚核(PBreL)。这些发现增进了我们对LPB组织结构的理解,并揭示Pdyn-IRES-Cre小鼠为遗传研究PBdL中被温暖激活的、FoxP2+谷氨酸能神经元提供了途径,其中许多神经元投射到下丘脑。
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