Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance
Open accessAbstract
Lateral habenula (LHb) projections to the ventral midbrain, including the rostromedial tegmental nucleus (RMTg), convey negative reward-related information, but the behavioral ramifications of selective activation of this pathway remain unexplored. We found that exposure to aversive stimuli in mice increased LHb excitatory drive onto RMTg neurons. Furthermore, optogenetic activation of this pathway promoted active, passive and conditioned behavioral avoidance. Thus, activity of LHb efferents to the midbrain is aversive but can also serve to negatively reinforce behavioral responding.
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Electrical stimulation of the lateral habenula output caused conditioned place aversions.
“Consistent with these observations, electrical stimulation of the lateral habenula output caused conditioned place aversions (Stamatakis and Stuber, 2012).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Stamatakis and Stuber, 2012
The passage indexed under Abstract reports conditioned place aversion in mice after stimulation of the LHb-to-RMTg pathway. However, it specifies optogenetic stimulation, not electrical stimulation; the Online Methods also describe laser stimulation. No page numbers are supplied in our copy. (LLM, conf=0.90)
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- Authors
- Stamatakis, A. M., & Stuber, G. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Stuber, Garret D
- Venue
- Nature Neuroscience
- Published
- 2012-06-24
- Volume
- 15
- Issue
- 8
- Pages
- 1105-1107
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3411914
- OpenAlex
- W1991236735
- Cited by
- 564
- References
- 20
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 41 · 2023: 33 · 2022: 32 · 2021: 37 · 2020: 48 · 2019: 41 · 2018: 50 · 2017: 48 · 2016: 48 · 2015: 39 · 2014: 46 · 2013: 35 · 2012: 10
- FWCI
- 17.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Foundation of Hope for Research and Treatment of Mental Illness
- National Institute on Drug Abuse (F31DA034472, R01DA032750, DA029325, R21DA029325, DA032750, R37DA032750)
- National Institute of Neurological Disorders and Stroke (P30NS045892, T32NS007431)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- lateral habenula, rostromedial tegmental nucleus, ventral midbrain, behavioral avoidance, aversive stimuli, negative rewards, optogenetic stimulation, avoidance conditioning, negative reinforcement
- MeSH terms
- Animals, Avoidance Learning, Behavior, Animal, Dopamine, Mice, Transgenic, Neural Pathways, Synaptic Transmission, Neurons, Reinforcement, Psychology, Ventral Tegmental Area, Habenula, Mice
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