5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors

Guangchen Ji, Wei Zhang, Lenin Mahimainathan, Madhusudhanan Narasimhan, Takaki Kiritoshi, Xiuzhen Fan, Jigong Wang, Thomas Green, Volker Neugebauer

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT2CR in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic-pain-related behaviors.

Original languageEnglish (US)
Pages (from-to)1378-1393
Number of pages16
JournalJournal of Neuroscience
Volume37
Issue number6
DOIs
StatePublished - Feb 8 2017

Fingerprint

Spinal Nerves
Neuralgia
Amygdala
Ligation
Neuronal Plasticity
Sensory Thresholds
Neurons
Anxiety Disorders
Cell Nucleus
Mental Disorders
Small Interfering RNA
Anxiety
Depression
Pain
Injections
Brain

Keywords

  • Amygdala
  • Depression
  • Pain
  • Plasticity
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ji, G., Zhang, W., Mahimainathan, L., Narasimhan, M., Kiritoshi, T., Fan, X., ... Neugebauer, V. (2017). 5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors. Journal of Neuroscience, 37(6), 1378-1393. https://doi.org/10.1523/JNEUROSCI.2468-16.2016

5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors. / Ji, Guangchen; Zhang, Wei; Mahimainathan, Lenin; Narasimhan, Madhusudhanan; Kiritoshi, Takaki; Fan, Xiuzhen; Wang, Jigong; Green, Thomas; Neugebauer, Volker.

In: Journal of Neuroscience, Vol. 37, No. 6, 08.02.2017, p. 1378-1393.

Research output: Contribution to journalArticle

Ji, G, Zhang, W, Mahimainathan, L, Narasimhan, M, Kiritoshi, T, Fan, X, Wang, J, Green, T & Neugebauer, V 2017, '5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors', Journal of Neuroscience, vol. 37, no. 6, pp. 1378-1393. https://doi.org/10.1523/JNEUROSCI.2468-16.2016
Ji, Guangchen ; Zhang, Wei ; Mahimainathan, Lenin ; Narasimhan, Madhusudhanan ; Kiritoshi, Takaki ; Fan, Xiuzhen ; Wang, Jigong ; Green, Thomas ; Neugebauer, Volker. / 5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors. In: Journal of Neuroscience. 2017 ; Vol. 37, No. 6. pp. 1378-1393.
@article{27f39387cb324f1a8b0688a07a712dfc,
title = "5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors",
abstract = "Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT2CR in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic-pain-related behaviors.",
keywords = "Amygdala, Depression, Pain, Plasticity, Serotonin",
author = "Guangchen Ji and Wei Zhang and Lenin Mahimainathan and Madhusudhanan Narasimhan and Takaki Kiritoshi and Xiuzhen Fan and Jigong Wang and Thomas Green and Volker Neugebauer",
year = "2017",
month = "2",
day = "8",
doi = "10.1523/JNEUROSCI.2468-16.2016",
language = "English (US)",
volume = "37",
pages = "1378--1393",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "6",

}

TY - JOUR

T1 - 5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors

AU - Ji, Guangchen

AU - Zhang, Wei

AU - Mahimainathan, Lenin

AU - Narasimhan, Madhusudhanan

AU - Kiritoshi, Takaki

AU - Fan, Xiuzhen

AU - Wang, Jigong

AU - Green, Thomas

AU - Neugebauer, Volker

PY - 2017/2/8

Y1 - 2017/2/8

N2 - Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT2CR in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic-pain-related behaviors.

AB - Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT2CR in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic-pain-related behaviors.

KW - Amygdala

KW - Depression

KW - Pain

KW - Plasticity

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=85012024823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012024823&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2468-16.2016

DO - 10.1523/JNEUROSCI.2468-16.2016

M3 - Article

VL - 37

SP - 1378

EP - 1393

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 6

ER -