Peptide-Mediated Neurotransmission Takes Center Stage

Gonzalez-Suarez, Aneysis D.; Nitabach, Michael N.

doi:10.1016/j.tins.2018.03.013

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…Neuromodulator molecules take many different chemical forms, including diatomic gases such as nitric oxide, lipid metabolites such as the endocannabinoids, and amino acids and their metabolites such as glutamate, GABA, acetylcholine, serotonin and dopamine. By far the largest family of neuromodulator molecules known, however, comprises the evolutionarily ancient proteinaceous signaling molecules known as neuropeptides (Baraban and Tallent, 2004; Burbach, 2011; Gonzalez-Suarez and Nitabach, 2018; Hökfelt et al, 2013; van den Pol, 2012; Wang et al, 2015). The most widely studied neuropeptides are the endogenous ‘opioid’ peptides - enkephalins, endorphins and dynorphins - but there are nearly one hundred other NPP genes in the human genome and numerous homologs are present in almost all known animal genomes (Elphick et al, 2018; Jékely, 2013).…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Smith

Sümbül

Graybuck

et al. 2019

eLife

125

149

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Seeking new insights into the homeostasis, modulation and plasticity of cortical synaptic networks, we have analyzed results from a single-cell RNA-seq study of 22,439 mouse neocortical neurons. Our analysis exposes transcriptomic evidence for dozens of molecularly distinct neuropeptidergic modulatory networks that directly interconnect all cortical neurons. This evidence begins with a discovery that transcripts of one or more neuropeptide precursor (NPP) and one or more neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes are highly abundant in all, or very nearly all, cortical neurons. Individual neurons express diverse subsets of NP signaling genes from palettes encoding 18 NPPs and 29 NP-GPCRs. These 47 genes comprise 37 cognate NPP/NP-GPCR pairs, implying the likelihood of local neuropeptide signaling. Here, we use neuron-type-specific patterns of NP gene expression to offer specific, testable predictions regarding 37 peptidergic neuromodulatory networks that may play prominent roles in cortical homeostasis and plasticity.

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Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Smith

Sümbül

Graybuck

et al. 2019

eLife

125

149

View full text Add to dashboard Cite

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“…The SDH neurons receive nociceptive messages from the periphery and transmit them to higher levels during these processing events, and the nociception in the dorsal horn receives multiple modulations from descending axons and local interneurons, making the dorsal horn a pivotal site for nociception processing and modulation (Todd, 2010). In addition to "classic" neurotransmitters, peptides (including NT) are also involved in nociception transmission and modulation (Fürst, 1999;Gonzalez-Suarez and Nitabach, 2018). Despite extensive studies on NT distribution in the spinal cord, previous reports have provided little information about the organization of NT-ir structures and their relationships with GABAergic neurons.…”

Section: Nt-immunoreactivity and Ntr2-ir In Spinal Dorsal Hornmentioning

confidence: 99%

Neurotensin Attenuates Nociception by Facilitating Inhibitory Synaptic Transmission in the Mouse Spinal Cord

Zhang

Feng

Qiu

et al. 2021

Front. Neural Circuits

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Neurotensin (NT) is an endogenous tridecapeptide in the central nervous system. NT-containing neurons and NT receptors are widely distributed in the spinal dorsal horn (SDH), indicating their possible modulatory roles in nociception processing. However, the exact distribution and function of NT, as well as NT receptors (NTRs) expression in the SDH, have not been well documented. Among the four NTR subtypes, NTR2 is predominantly involved in central analgesia according to previous reports. However, the expression and function of NTR2 in the SDH has not yet been directly elucidated. Specifically, it remains unclear how NT-NTR2 interactions contribute to NT-mediated analgesia. In the present study, by using immunofluorescent histochemical staining and immunohistochemical staining with in situ hybridization histochemical staining, we found that dense NT- immunoreactivity (NT-ir) and moderate NTR2-ir neuronal cell bodies and fibers were localized throughout the superficial laminae (laminae I-II) of the SDH at the light microscopic level. In addition, γ-aminobutyric acid (GABA) and NTR2 mRNA were colocalized in some neuronal cell bodies, predominantly in lamina II. Using confocal and electron microscopy, we also observed that NT-ir terminals made both close contacts and asymmetrical synapses with the local GABA-ir neurons. Second, electrophysiological recordings showed that NT facilitated inhibitory synaptic transmission but not glutamatergic excitatory synaptic transmission. Inactivation of NTR2 abolished the NT actions on both GABAergic and glycinergic synaptic release. Moreover, a behavioral study revealed that intrathecal injection of NT attenuated thermal pain, mechanical pain, and formalin induced acute inflammatory pain primarily by activating NTR2. Taken together, the present results provide direct evidence that NT-containing terminals and fibers, as well as NTR2-expressing neurons are widely distributed in the spinal dorsal horn, GABA-containing neurons express NTR2 mainly in lamina II, GABA coexists with NTR2 mainly in lamina II, and NT may directly increase the activity of local inhibitory neurons through NTR2 and induce analgesic effects.

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“…For instance, many GABAergic neurons contain both somatostatin and NPY in hippocampus DG [212]. Understanding how peptidergic systems coordinate their activities to regulate network functioning represents an unsolved yet exciting issue in the field of neuroscience [121,215].…”

Section: Retina and Hippocampus: Common Themesmentioning

confidence: 99%

Molecular and Cellular Mechanisms Underlying Somatostatin-Based Signaling in Two Model Neural Networks, the Retina and the Hippocampus

Cammalleri

Bagnoli

Bigiani

2019

IJMS

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Neural inhibition plays a key role in determining the specific computational tasks of different brain circuitries. This functional “braking” activity is provided by inhibitory interneurons that use different neurochemicals for signaling. One of these substances, somatostatin, is found in several neural networks, raising questions about the significance of its widespread occurrence and usage. Here, we address this issue by analyzing the somatostatinergic system in two regions of the central nervous system: the retina and the hippocampus. By comparing the available information on these structures, we identify common motifs in the action of somatostatin that may explain its involvement in such diverse circuitries. The emerging concept is that somatostatin-based signaling, through conserved molecular and cellular mechanisms, allows neural networks to operate correctly.

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Peptide-Mediated Neurotransmission Takes Center Stage

Cited by 9 publications

References 14 publications

Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Neurotensin Attenuates Nociception by Facilitating Inhibitory Synaptic Transmission in the Mouse Spinal Cord

Molecular and Cellular Mechanisms Underlying Somatostatin-Based Signaling in Two Model Neural Networks, the Retina and the Hippocampus

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