Input-output connections of LJA5 prodynorphin neurons.

Input-output connections of LJA5 prodynorphin neurons.
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LJA 5前强啡肽神经元的输入-输出连接。

DOI:
10.1002/cne.24974
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发表时间:
2021-03
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Bassuk AG
Bassuk AG
中科院分区:
其他
文献类型:
--
作者:
Agostinelli LJ;Mix MR;Hefti MM;Scammell TE;Bassuk AG

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感觉信息从周围神经传递,通过脊髓,直至大脑。感觉信息可以通过从大脑到脊髓的投射来调节,但自上而下的感觉控制的神经基础尚不完全清楚。我们在小鼠脑干中发现了一个新的抑制性神经元群体,其特征是强啡肽原的表达,我们将其命名为 LJA5。在这里,我们在人类脑干中识别出一组类似的 Pdyn+ 神经元,并定义了小鼠 LJA5 神经元的传出和传入投射模式。使用特定的遗传工具,我们选择性地追踪表达 Pdyn 的 LJA5 神经元在大脑和脊髓中的投射。终末野在导水管周围灰质(PAG)的外侧和腹外侧、臂旁核(LPB)、尾部加压区、三叉神经脊椎核的 I 层和脊髓的各个层面最密集。然后,我们标记了 PAG、LPB​​、髓质和脊髓中的细胞类型,以更好地定义 LJA5 bouton 的具体目标。 LJA5 神经元专门向脊髓 I 层发送唯一已知的抑制性下行投射,将传入的疼痛、温度和瘙痒信息传递到大脑。通过逆行追踪,我们发现 LJA5 神经元接收来自感觉和应激区域的输入,例如体感/岛叶皮层、视前区、室旁核、背内侧核和外侧下丘脑、PAG 和 LPB。这种输入和输出模式表明 LJA5 神经元具有独特的位置,可以被感觉和压力激活,进而抑制疼痛和瘙痒。我们在小鼠和人类脑干中发现了一个新的抑制性强啡肽原神经元群,我们将其命名为 LJA5。 LJA5 神经元选择性地靶向脊髓 I 层和其他感觉核,包括外侧臂旁灰质和导水管周围灰质。 LJA5 区域接收来自感觉和压力区域的输入。
Sensory information is transmitted from peripheral nerves, through the spinal cord, and up to the brain. Sensory information may be modulated by projections from the brain to the spinal cord, but the neural substrates for top‐down sensory control are incompletely understood. We identified a novel population of inhibitory neurons in the mouse brainstem, distinguished by their expression of prodynorphin, which we named LJA5. Here, we identify a similar group of Pdyn+ neurons in the human brainstem, and we define the efferent and afferent projection patterns of LJA5 neurons in mouse. Using specific genetic tools, we selectively traced the projections of the Pdyn‐expressing LJA5 neurons through the brain and spinal cord. Terminal fields were densest in the lateral and ventrolateral periaqueductal gray (PAG), lateral parabrachial nucleus (LPB), caudal pressor area, and lamina I of the spinal trigeminal nucleus and all levels of the spinal cord. We then labeled cell types in the PAG, LPB, medulla, and spinal cord to better define the specific targets of LJA5 boutons. LJA5 neurons send the only known inhibitory descending projection specifically to lamina I of the spinal cord, which transmits afferent pain, temperature, and itch information up to the brain. Using retrograde tracing, we found LJA5 neurons receive inputs from sensory and stress areas such as somatosensory/insular cortex, preoptic area, paraventricular nucleus, dorsomedial nucleus and lateral hypothalamus, PAG, and LPB. This pattern of inputs and outputs suggest LJA5 neurons are uniquely positioned to be activated by sensation and stress, and in turn, inhibit pain and itch. We identified a novel population of inhibitory prodynorphin neurons in the mouse and human brainstem which we named LJA5. LJA5 neurons selectively target lamina I of the spinal cord, and other sensory nuclei including the lateral parabrachial and periaqueductal gray. The LJA5 area receives input from sensory and stress regions.
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