Novel genetically encoded tools for imaging or silencing neuropeptide release from presynaptic terminals<i>in vivo</i>

Kim, Dong-Il; Park, Sekun; Ye, Mao; Chen, Jane; Jhang, Jinho; Hunker, Avery C.; Zweifel, Larry S.; Palmiter, Richard D.; Han, Sung

doi:10.1101/2023.01.19.524797

Cited by 8 publications

(5 citation statements)

References 68 publications

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“…The glutamate signaling from the CGRP PBN neurons is likely to be the most relevant transmitter, because the receptors for some of neuropeptides (CGRP, NTS, PACAP and Substance P) made by CGRP PBN neurons were not detected in the VPMpc. In contrast, neuropeptide signaling from CGRP PBN neurons to the central nucleus of the amygdala is critical for fear learning and memory 42 .…”

Section: Discussionmentioning

confidence: 97%

Gustatory Thalamic Neurons Mediate Aversive Behaviors

Cao,

Park,

Pauli

et al. 2024

Preprint

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The parvicellular part of the ventral posteromedial nucleus (VPMpc) of the thalamus, also known as the gustatory thalamus, receives input from the parabrachial nucleus and relays taste sensation to the gustatory (or insular) cortex. Prior research has focussed on the role of the VPMpc in relaying taste signals. Here we provide evidence showing that VPMpc also mediates aversive behaviors. By recording calcium transients in vivo from single neurons in mice, we show that neurons expressing cholecystokinin and the mu-opioid receptor in the VPMpc respond to various noxious stimuli and fear memory. Chemogenetic and optogenetic activation of these neurons enhances the response to aversive stimuli, whereas silencing them attenuates aversive behaviors. The VPMpc neurons directly innervate neurons in the insular cortex and rostral lateral amygdala. This study expands the role of the VPMpc to include mediating aversive and threating signals to the insular cortex and lateral amygdala.

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Section: Discussionmentioning

confidence: 97%

Gustatory Thalamic Neurons Mediate Aversive Behaviors

Cao,

Park,

Pauli

et al. 2024

Preprint

Self Cite

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“…For example, the development of effective migraine therapeutics targeting CGRPα or its receptor confirm the important role this peptide plays in headache (De Matteis et al, 2020 ;Tso and Goadsby, 2017 ) Beyond Substance P and CGRPα, pain-responsive neurons express a rich repertoire of potential signaling molecules, including other neuropeptides. Emerging approaches to image and manipulate these molecules (Girven et al, 2022 ;Kim et al, 2023 ), as well as advances in quantitating pain behaviors (Bohic et al, 2023 ;MacDonald and Chesler, 2023 ), may ultimately reveal the fundamental roles of neuropeptides in generating our experience of pain.…”

Section: Discussionmentioning

confidence: 99%

Pain persists in mice lacking both Substance P and CGRPα signaling

MacDonald,

Jayabalan,

Seaman

et al. 2024

Preprint

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The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides and their receptors are expressed at high levels in pain-responsive neurons from the periphery to the brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve pain in clinical trials. Since Substance P and CGRPα are extensively co-expressed we hypothesized that their simultaneous inhibition would be required for effective analgesia. We therefore generated Tac1 and Calca double knockout (DKO) mice and assessed their behavior using a wide range of pain-relevant assays. As expected, Substance P and CGRPα peptides were undetectable throughout the nervous system of DKO mice. To our surprise, these animals displayed largely intact responses to mechanical, thermal, chemical, and visceral pain stimuli, as well as itch. Moreover, chronic inflammatory pain and neurogenic inflammation were unaffected by loss of the two peptides. Finally, neuropathic pain evoked by nerve injury or chemotherapy treatment was also preserved in peptide-deficient mice. Thus, our results demonstrate that even in combination, Substance P and CGRPα are not required for the transmission of acute and chronic pain.

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“…Beyond Substance P and CGRPα, pain-responsive neurons express a rich repertoire of potential signaling molecules, including other neuropeptides. Emerging approaches to image and manipulate these molecules (Girven et al, 2022; Kim et al, 2023), as well as advances in quantitating pain behaviors (Bohic et al, 2023; MacDonald and Chesler, 2023), may ultimately reveal the fundamental roles of neuropeptides in generating our experience of pain.…”

Section: Discussionmentioning

confidence: 99%

Pain persists in mice lacking both Substance P and CGRPα signaling

MacDonald,

Jayabalan,

Seaman

et al. 2023

Preprint

View full text Add to dashboard Cite

SummaryThe neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides and their receptors are expressed at high levels in pain-responsive neurons from the periphery to the brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve pain in clinical trials. Since Substance P and CGRPα are extensively co-expressed we hypothesized that their simultaneous inhibition would be required for effective analgesia. We therefore generatedTac1andCalcadouble knockout (DKO) mice and assessed their behavior using a wide range of pain-relevant assays. As expected, Substance P and CGRPα peptides were undetectable throughout the nervous system of DKO mice. To our surprise, these animals displayed largely intact responses to mechanical, thermal, chemical, and visceral pain stimuli, as well as itch. Moreover, chronic inflammatory pain and neurogenic inflammation were unaffected by loss of the two peptides. Finally, neuropathic pain evoked by nerve injury or chemotherapy treatment was also preserved in peptide-deficient mice. Thus, our results demonstrate that even in combination, Substance P and CGRPα are not required for the transmission of acute and chronic pain.

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Novel genetically encoded tools for imaging or silencing neuropeptide release from presynaptic terminalsin vivo

Cited by 8 publications

References 68 publications

Gustatory Thalamic Neurons Mediate Aversive Behaviors

Gustatory Thalamic Neurons Mediate Aversive Behaviors

Pain persists in mice lacking both Substance P and CGRPα signaling

Pain persists in mice lacking both Substance P and CGRPα signaling

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