Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
J Comp Neurol. 2021 Feb;529(3):635-654. doi: 10.1002/cne.24974. Epub 2020 Jul 24.
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.
感觉信息由外周神经传递，经过脊髓，最终到达大脑。感觉信息可能会受到来自大脑投射到脊髓的信号的调制，但对于这种自上而下的感觉控制的神经基础还不完全了解。我们在小鼠脑干中发现了一种新型抑制性神经元群体，其特征在于表达前强啡肽原（prodynorphin），我们将其命名为 LJA5。在这里，我们在人类脑干中鉴定出了类似的 Pdyn+神经元群体，并确定了 LJA5 神经元在小鼠中的传出和传入投射模式。使用特定的遗传工具，我们选择性地追踪了表达 Pdyn 的 LJA5 神经元在大脑和脊髓中的投射。终末场在外侧和腹外侧导水管周围灰质（periaqueductal gray，PAG）、外侧臂旁核（lateral parabrachial nucleus，LPB）、加压区尾端和三叉神经感觉核 I 层以及脊髓的所有水平最为密集。然后，我们标记了 PAG、LPB、延髓和脊髓中的细胞类型，以更好地定义 LJA5 末梢的特定靶点。LJA5 神经元发出唯一已知的抑制性下行投射，专门投射到脊髓 I 层，该层将传入的疼痛、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，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 神经元独特地定位于被感觉和应激激活，进而抑制疼痛和瘙痒。
