ArticleNature medicine2016
Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
104 citing papers in PubMed, 4 syntheses or guidelines pooled it, 172 citations in OpenAlex.
- The disappointment centre of the brain gets exciting: a systematic review of habenula dysfunction in depression.Translational psychiatry · 2024Pooled it
- Response Flexibility: The Role of the Lateral Habenula.Frontiers in behavioral neuroscience · 2022Pooled it
- Circadian Influences on the Habenula and Their Potential Contribution to Neuropsychiatric Disorders.Frontiers in behavioral neuroscience · 2021Pooled it
- Deep Brain Stimulation of the Habenula: Systematic Review of the Literature and Clinical Trial Registries.Frontiers in psychiatry · 2021Pooled it
- Trial
- Prefrontal-raphe-habenular circuit drives fear memory recall and updating.Nature communications · 2026Article
- NAcLat-DBS reduces GABANeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- A dual-pathway dysregulation in prefrontal-habenular circuits mediates stress susceptibility.Nature communications · 2026Article
- Somatostatin-expressing neurons in the zona incerta regulate chronic stress response and modulate depression-like behaviors.Molecular psychiatry · 2026Article
- Stress resilience is associated with transcriptional remodeling in the VTA.Cell reports · 2026Article
- The Habenula's role in major depressive disorder: recent insights from preclinical and human studies.Translational psychiatry · 2026Review
- Estrogen receptor beta in lateral habenula mediates antidepressant effects of estrogen in postpartum-hormone-withdrawal-induced depression.Molecular psychiatry · 2026Article
- Neural signaling mechanisms in depression: bridging classical monoamine hypotheses, animal models, and emerging antidepressant strategies.Frontiers in cell and developmental biology · 2026Review
- Stress resilience is associated with transcriptional remodeling in the VTA.bioRxiv : the preprint server for biology · 2025Article
- Depression exacerbates AD pathology through lactate-dependent activation of microglial Kv1.3 to promote Aβ-containing exosome spreading.Journal of neuroinflammation · 2025Article
- Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.NPJ Parkinson's disease · 2025Article
- GABAMedComm · 2025Review
- Neuron-non-neuron electrical coupling networks are involved in chronic stress-induced electrophysiological changes in lateral habenular neurons.The Journal of physiology · 2025Article
- Article
- Upregulated inwardly rectifying KJournal of biomedical research · 2025Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lateral habenula (LHb) encodes aversive signals, and its aberrant activity contributes to depression-like symptoms. However, a limited understanding of the cellular mechanisms underlying LHb hyperactivity has precluded the development of pharmacological strategies to ameliorate depression-like phenotypes. Here we report that an aversive experience in mice, such as foot-shock exposure (FsE), induces LHb neuronal hyperactivity and depression-like symptoms. This occurs along with increased protein phosphatase 2A (PP2A) activity, a known regulator of GABAB receptor (GABABR) and G protein-gated inwardly rectifying potassium (GIRK) channel surface expression. Accordingly, FsE triggers GABAB1 and GIRK2 internalization, leading to rapid and persistent weakening of GABAB-activated GIRK-mediated (GABAB-GIRK) currents. Pharmacological inhibition of PP2A restores both GABAB-GIRK function and neuronal excitability. As a consequence, PP2A inhibition ameliorates depression-like symptoms after FsE and in a learned-helplessness model of depression. Thus, GABAB-GIRK plasticity in the LHb represents a cellular substrate for aversive experience. Furthermore, its reversal by PP2A inhibition may provide a novel therapeutic approach to alleviate symptoms of depression in disorders that are characterized by LHb hyperactivity.
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Registered trials
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 Socratic graph.