The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
Open accessAbstract
The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.
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“Excitatory synapses onto LHb cells are characterized by a high ratio of AMPAR-to NMDAR-mediated synaptic responses [255], indicative of low levels of NMDAR expression.”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [255]
In the citing paper
“LHb neurons also receive feed-forward and feedback GABAergic inhibition [253,255].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [255]
In the citing paper
“An increased probability of presynaptic glutamate release in the LHb accompanies learned helplessness and chronic restraint stress [255,260].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [255]
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Citations
Cites
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“…helplessness models of depression, presynaptic potentiation at excitatory synapses onto VTA-projecting LHb neurons mediates an animal’s helplessness behaviour, and depletion of transmitter release by repeated electrical stimulation of LHb afferents rescues learned helplessness (Li et al., 2011).”
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BindingDB Entry 50011888: Repurposing of Drugs-The Ketamine Story.
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Metadata
- Authors
- Li, B., Piriz, J., Mirrione, M., Chung, C., Proulx, C. D., Schulz, D., Henn, F., & Malinow, R.
- Affiliations
- University of California San Diego (US)
- Brookhaven National Laboratory (US)
- Corresponding author
- Li, Bo
- Malinow, Roberto
- Venue
- Nature
- Published
- 2011-02
- Volume
- 470
- Issue
- 7335
- Pages
- 535-539
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3285101
- OpenAlex
- W1969186778
- Cited by
- 634
- References
- 34
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 61 · 2023: 33 · 2022: 50 · 2021: 49 · 2020: 47 · 2019: 56 · 2018: 41 · 2017: 47 · 2016: 50 · 2015: 31 · 2014: 38 · 2013: 33 · 2012: 29
- FWCI
- 25.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institute on Aging (R01AG032132)
- National Institute of Mental Health (R01MH091119, R01MH049159, R01MH091903)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- lateral habenula, learned helplessness, depression, synaptic potentiation, presynaptic release probability, ventral tegmental area, deep brain stimulation, negative rewards, aversive outcomes, dopamine, excitatory synapses
- MeSH terms
- Animals, Avoidance Learning, Depression, Disease Models, Animal, Dopamine, Electric Stimulation, Helplessness, Learned, Male, Models, Neurological, Synaptic Transmission, Neurons, Reward, Synapses, Thalamus, Rats, Sprague-Dawley, Ventral Tegmental Area, Presynaptic Terminals, Excitatory Postsynaptic Potentials, Deep Brain Stimulation, Rats, Neuroanatomical Tract-Tracing Techniques
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