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核心技术专利:CN118964589B侵权必究
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孤束核到腹侧被盖区投射神经元的特征揭示了高阶突触组织和对胆囊收缩素的不同反应性。

Characterization of NTS-to-VTA projection neurons reveals higher-order synaptic organization and distinct responsiveness to cholecystokinin.

作者信息

Ritchey Caitlin R, Rossi David J, Peters James H

机构信息

Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.

出版信息

J Physiol. 2025 Sep;603(17):4817-4843. doi: 10.1113/JP288729. Epub 2025 Aug 10.


DOI:10.1113/JP288729
PMID:40785037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12400789/
Abstract

The midbrain ventral tegmental area (VTA) shapes goal-oriented behaviours, including food intake, via dense dopaminergic projections to many key forebrain areas. In addition, the VTA serves as an integrator of neural inputs from throughout the brain that modulate VTA output to produce broad, state-dependent, changes that reflect the balance of internal and external considerations. The brainstem nucleus of the solitary tract (NTS) is the primary site for integration of viscerosensory and taste information conveyed through the cranial nerves and is essential for the control of food intake. Importantly, the NTS has been shown to form direct connections with the VTA, but little is known about the anatomical and neurophysiological nature of these projecting neurons. Using VTA-targeted retrobead injections, we characterized a subpopulation of NTS neurons that form monosynaptic connections to the VTA distributed across all levels of the nucleus, with higher counts in the medial and caudal NTS. VTA-projecting NTS neurons were largely catecholaminergic and/or GLP-1 containing, with the majority also expressing VGlut2, consistent with an excitatory glutamatergic phenotype. Functionally, VTA-projecting NTS neurons had noticeably different neurophysiological properties compared with unlabelled NTS neurons, with the majority being polysynaptically (higher-order) coupled to the viscerosensory afferents. Moreover, in contrast to unlabelled neurons, recorded VTA-projecting NTS neurons were largely inhibited by the feeding peptide cholecystokinin (CCK). Together, these findings demonstrate the distinct phenotypic and functional properties of VTA-projecting NTS neurons that may play a role in regulating mesolimbic output to control appetitive feeding responses. KEY POINTS: Ventral tegmental area (VTA)-projecting nucleus of the solitary tract (NTS) neurons are distributed rostro-caudally throughout the nucleus and express tyrosine hydroxylase and/or glucagon-like peptide-1 (GLP-1). VTA-projecting NTS neurons are higher order, receiving indirect, polysynaptic vagal afferent input. Most VTA-projecting NTS neurons are inhibited by cholecystokinin.

摘要

中脑腹侧被盖区(VTA)通过向许多关键前脑区域密集投射多巴胺能纤维,塑造包括食物摄入在内的目标导向行为。此外,VTA作为来自全脑的神经输入的整合中心,调节VTA输出,以产生广泛的、依赖状态的变化,反映内部和外部因素的平衡。孤束核(NTS)是通过脑神经传递的内脏感觉和味觉信息整合的主要部位,对食物摄入的控制至关重要。重要的是,已证明NTS与VTA形成直接连接,但对这些投射神经元的解剖学和神经生理学特性知之甚少。使用靶向VTA的逆行珠注射,我们对NTS神经元的一个亚群进行了特征描述,这些神经元与分布在整个核各水平的VTA形成单突触连接,在内侧和尾侧NTS中的数量更多。投射到VTA的NTS神经元大多含有儿茶酚胺能和/或胰高血糖素样肽-1(GLP-1),大多数还表达VGlut2,与兴奋性谷氨酸能表型一致。在功能上,与未标记的NTS神经元相比,投射到VTA的NTS神经元具有明显不同的神经生理学特性,大多数与内脏感觉传入纤维多突触(高阶)耦合。此外,与未标记的神经元相比,记录到的投射到VTA的NTS神经元在很大程度上受到进食肽胆囊收缩素(CCK)的抑制。总之,这些发现证明了投射到VTA的NTS神经元具有独特的表型和功能特性,可能在调节中脑边缘输出以控制食欲性进食反应中发挥作用。要点:投射到腹侧被盖区(VTA)的孤束核(NTS)神经元在整个核内从头端到尾端分布,并表达酪氨酸羟化酶和/或胰高血糖素样肽-1(GLP-1)。投射到VTA的NTS神经元是高阶的,接受间接的、多突触的迷走神经传入输入。大多数投射到VTA的NTS神经元受到胆囊收缩素的抑制。

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本文引用的文献

[1]
Functionally distinct evoked and spontaneous neurotransmission operate via a shared pool of synaptic vesicles in viscerosensory afferents.

J Physiol. 2025-5

[2]
GLP-1 receptor agonist exendin-4 suppresses food intake by inhibiting hindbrain orexigenic NPY neurons.

Am J Physiol Endocrinol Metab. 2025-5-1

[3]
An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking.

Sci Adv. 2025-2-28

[4]
Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract.

Mol Metab. 2025-1

[5]
Viscerosensory signalling to the nucleus accumbens via the solitary tract nucleus.

J Neurochem. 2024-9

[6]
Dissociable hindbrain GLP1R circuits for satiety and aversion.

Nature. 2024-8

[7]
Populations of Hindbrain Glucagon-Like Peptide 1 (GLP1) Neurons That Innervate the Hypothalamic PVH, Thalamic PVT, or Limbic Forebrain BST Have Axon Collaterals That Reach All Central Regions Innervated by GLP1 Neurons.

J Neurosci. 2024-7-31

[8]
CCK-sensitive C fibers activate NTS leptin receptor-expressing neurons via NMDA receptors.

Am J Physiol Regul Integr Comp Physiol. 2024-5-1

[9]
Dopamine neuron activity evoked by sucrose and sucrose-predictive cues is augmented by peripheral and central manipulations of glucose availability.

Eur J Neurosci. 2024-5

[10]
TRPV1 enhances cholecystokinin signaling in primary vagal afferent neurons and mediates the central effects on spontaneous glutamate release in the NTS.

Am J Physiol Cell Physiol. 2024-1-1

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