βCaMKII in Lateral Habenula Mediates Core Symptoms of Depression
Open accessAbstract
Depression and the Habenula: The lateral habenula (LHb) appears to have a role in depression. However, the underlying mechanisms are poorly understood, and by using multiple rodent models of depression, Li et al. (p. 1016 ) identified a signaling pathway and associated neuronal adaptations in which the enzyme βCaMKII was selectively up-regulated in the LHb. Manipulations that enhanced βCaMKII levels increased depression-related phenotypes, and RNA interference of CaMKIIb blunted depression. Enhanced βCaMKII levels in the habenula promoted excitatory synaptic transmission on these neurons and increased action potential firing mediated by an up-regulation of a specific subtype of glutamate receptors.
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Viral knockdown of beta-CaMK, the enzyme underlying stress-induced presynaptic potentiation of lateral habenula excitatory synapses, prevents forced swim and learned helplessness behaviors in congenitally learned helpless rats.
“Viral knockdown of beta-CaMK, the enzyme underlying the stress-induced presynaptic potentiation of LHb excitatory synapses, prevented forced swim and learned helplessness behaviors in congenitally learned helpless rats [267].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [267]
Selective activity-dependent potentiation of synapses formed by lateral hypothalamic axons onto lateral habenula neurons promotes lateral habenula discharge and is sufficient to mimic chronic stress behavioral effects in the forced swim and sucrose preference tests.
“Selective activity-dependent potentiation of synapses formed by axons of LH neurons with LHb neurons promoted LHb discharge and was sufficient to induce mimic the behavioral effects of chronic stress in the forced swim and sucrose preference tests [260, 267].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [267]
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- Authors
- Li, K., Zhou, T., Liao, L., Yang, Z., Wong, C., Henn, F., Malinow, R., Yates, J. R., & Hu, H.
- Affiliations
- Chinese Academy of Sciences (CN)
- Scripps Research Institute (US)
- Cold Spring Harbor Laboratory (US)
- University of California San Diego (US)
- Corresponding author
- Li, Kun
- Zhou, Tao
- Hu, Hailan
- Venue
- Science
- Published
- 2013-08-30
- Volume
- 341
- Issue
- 6149
- Pages
- 1016-1020
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3932364
- OpenAlex
- W2154579172
- Cited by
- 411
- References
- 54
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 37 · 2023: 38 · 2022: 37 · 2021: 32 · 2020: 32 · 2019: 37 · 2018: 37 · 2017: 37 · 2016: 34 · 2015: 18 · 2014: 24 · 2013: 4
- FWCI
- 19.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH091119, R01MH067880)
- National Institute of General Medical Sciences (P41GM103533)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- lateral habenula, depression, anhedonia, behavioral despair, GluR1, synaptic efficacy, antidepressants, calcium/calmodulin-dependent protein kinase, glutamate receptors, neuronal hyperactivity
- MeSH terms
- Animals, Antidepressive Agents, Major Depressive Disorder, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Neurons, Promoter Regions, Genetic, Rats, Sprague-Dawley, Habenula, Proteomics, Mice, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Gene Knockdown Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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