Reward processing by the lateral habenula in normal and depressive behaviors
Open accessAbstract
The brain reward circuit has a central role in reinforcing behaviors that are rewarding and preventing behaviors that lead to punishment. Recent work has shown that the lateral habenula is an important part of the reward circuit by providing 'negative value' signals to the dopaminergic and serotonergic systems. Studies have also suggested that dysfunction of the lateral habenula is associated with psychiatric disorders, including major depression. Here, we discuss insights gained from neuronal recordings in monkeys regarding how the lateral habenula processes reward-related information. We then highlight recent optogenetic experiments in rodents addressing normal and abnormal functions of the habenula. Finally, we discuss how deregulation of the lateral habenula may be involved in depressive behaviors.
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Over-activation of the lateral habenula has been proposed to be involved in depression and as a site of antidepressant action of conventional antidepressant drugs.
“The lateral habenula signals negative valence to monoaminergic systems and over-activation of the lateral habenula has recently been proposed to be involved in depression as well as to be a site of antidepressant action of conventional antidepressant drugs (Proulx et al., 2014; Sartorius and Henn, 2007).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Proulx et al., 2014
The ‘Lateral habenula in depressive disorders’ section says LHb hyperactivity may contribute to depression. It also reports that chronic antidepressant treatment altered inputs to LHb neurons, but the available passage cuts off before describing the full result; the Conclusions propose pharmacological reduction of LHb hyperactivity as a future opportunity. These passages do not establish that the LHb is a site of action of conventional antidepressant drugs. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe lateral habenula signals negative valence to monoaminergic systems.
“The lateral habenula signals negative valence to monoaminergic systems and over-activation of the lateral habenula has recently been proposed to be involved in depression as well as to be a site of antidepressant action of conventional antidepressant drugs (Proulx et al., 2014; Sartorius and Henn, 2007).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Proulx et al., 2014
Abnormal activity in the lateral dorsal habenula is an important correlate of clinical depression.
“Abnormal activity in the lateral dorsal habenula is an important correlate of clinical depression (Proulx et al., 2014).”
From Social functioning in major depressive disorder (2016) · cites this paper as Proulx et al., 2014
LHb neurons increase their activity when adverse outcomes occur or are predicted and provide disynaptic inhibitory input to VTA DANs.
“LHb neurons increase their activity when adverse outcomes occur or are predicted and provide a disynaptic inhibitory (-GABAergic) input to VTA DANs.125,126”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [125]
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- Authors
- Proulx, C. D., Hikosaka, O., & Malinow, R.
- Affiliations
- University of California San Diego (US)
- National Institutes of Health (US)
- Corresponding author
- Proulx, Christophe D
- Venue
- Nature Neuroscience
- Published
- 2014-08-26
- Volume
- 17
- Issue
- 9
- Pages
- 1146-1152
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4305435
- OpenAlex
- W2013001152
- Cited by
- 461
- References
- 96
- Citations by year
- 2026: 30 · 2025: 42 · 2024: 42 · 2023: 30 · 2022: 52 · 2021: 37 · 2020: 37 · 2019: 47 · 2018: 34 · 2017: 50 · 2016: 37 · 2015: 20 · 2014: 2
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH091119)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- lateral habenula, reward processing, depression, brain reward circuits, dopaminergic system, serotonergic system, optogenetics, non-human primates, rodents
- MeSH terms
- Animals, Depressive Disorder, Major, Major Depressive Disorder, Dopamine, Humans, Reward, Serotonin, Habenula
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.
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