Evidence map›Paper›PMID 33344720›Full record

ArticleNeurobiology of stress2020

Early life stress dysregulates kappa opioid receptor signaling within the lateral habenula.

Sarah C Simmons, Ryan D Shepard, Shawn Gouty, Ludovic D Langlois, William J Flerlage, Brian M Cox, Fereshteh S Nugent

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of stress, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
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  12. Effects of early life stress and subsequent re-exposure to stress on neuronal activity in the lateral habenula.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
  13. Review
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  19. Review
  20. Acetaldehyde Excitation of Lateral Habenular Neurons via Multiple Cellular Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Sarah C SimmonsUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
Ryan D ShepardUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
Shawn GoutyUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
Ludovic D LangloisUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
William J FlerlageUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
Brian M CoxUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
Fereshteh S NugentUniformed Services University of the Health Sciences, Edward Hebert School of Medicine, Department of Pharmacology and Molecular Therapeutics, Bethesda, MD, 20814, USA.
Uniformed Services University of the Health Sciences · US

Funding

Effects of early life stress on synaptic function and DA signaling in the VTAR01DA039533 · NIDA · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI NUGENT, FERESHTEH S · 2015 to 2019
$1.8M
6 · The paper itself

Abstract

The lateral habenula (LHb) is an epithalamic brain region associated with value-based decision making and stress evasion through its modulation of dopamine (DA)-mediated reward circuitry. Specifically, increased activity of the LHb is associated with drug addiction, schizophrenia and stress-related disorders such as depression, anxiety and posttraumatic stress disorder. Dynorphin (Dyn)/Kappa opioid receptor (KOR) signaling is a mediator of stress response in reward circuitry. Previously, we have shown that maternal deprivation (MD), a severe early life stress, increases LHb spontaneous neuronal activity and intrinsic excitability while blunting the response of LHb neurons to extrahypothalamic corticotropin-releasing factor (CRF) signaling, another stress mediator. CRF pathways also interact with Dyn/KOR signaling. Surprisingly, there has been little study of direct KOR regulation of the LHb despite its distinct role in stress, reward and aversion processing. To test the functional role of Dyn/KOR signaling in the LHb, we utilized ex-vivo electrophysiology combined with pharmacological tools in rat LHb slices. We show that activation of KORs by a KOR agonist (U50,488) exerted differential effects on the excitability of two distinct sub-populations of LHb neurons that differed in their expression of hyperpolarization-activated cation currents (HCN, Ih). Specifically, KOR stimulation increased neuronal excitability in LHb neurons with large Ih currents (Ih+) while decreasing neuronal excitability in small/negative Ih (Ih-) neurons. We found that an intact fast-synaptic transmission was required for the effects of U50,488 on the excitability of both Ih- and Ih+ LHb neuronal subpopulations. While AMPAR-, GABA

Indexed as

action potential, (AP)adverse childhood experiences, (ACE)artificial cerebral spinal fluid, (ACSF)corticotropin-releasing factor, (CRF)dopamine, (DA)Dynorphindynorphin, (Dyn)Early life stressearly life stress, (ELS)fastafterhyperpolarization, (fAHP)hyperpolarization activated cation current, (HCN, Ih)input resistance, (Rin)inter-event interval, (IEI)Kappa opioid receptorKappa opioid receptor, (KOR)KORLateral habenulaLHbmaternal deprivation, (MD)medium afterhyperpolarization, (mAHP)miniature excitatory postsynaptic current, (mEPSC)miniature inhibitory postsynaptic current, (mIPSC)non-maternally deprived, (non-MD)nucleus accumbens, (NAc)postnatal age, (PN)raphe nuclei, (RN)rostromedial tegmental area, (RMTg)serotonin, (5HT)ventral tegmental area, (VTA)

Identifiers

PMID33344720
PMCPMC7739170
OpenAlexW3099103659

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.