Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat
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Neurons in the lateral habenula (LHb) of rats have efferent projections that terminate in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), where cell bodies of dopamine-containing neurons are located. In order to study the influence of the habenula on dopaminergic activity, single-cell electrophysiological techniques were used to record unit discharge of dopamine-containing neurons in the SNC and VTA during electrical stimulation of the LHb or adjacent structures. Dopamine-containing neurons in the SNC and VTA were identified by their characteristic spike duration (greater than 2 msec), discharge rate (2-8 spikes/sec), and irregular firing pattern. Analysis of peristimulus time histograms showed that 85% of SNC cells and 91% of VTA neurons were inhibited after single pulse stimulation (0.25 mA, 0.1 msec) of the LHb. The mean time between stimulation and onset of inhibition was 11 msec (range, 2-22 msec) and mean duration of maximal suppression was 76 msec (range, 20-250 msec). Stimulation of structures adjacent to the LHb (hippocampus, lateral thalamus, medial dorsal thalamus, medial habenula) had little or no effect. Destruction of the fasciculus retroflexus, the fiber pathway that contains most habenular efferents, blocked the stimulation effects on dopamine-containing neurons. Destruction of the stria medullaris, which contains most habenular afferents, did not alter the inhibitory effect of habenular stimulation. Injection of a cytotoxin, kainic acid, in the LHb 1 week before recording sessions blocked the inhibitory consequences of habenular stimulation. These experiments show that activation of neuronal perikarya in the LHb causes orthodromic inhibition of dopamine-containing neurons in SNC and VTA via the fasciculus retroflexus.
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Electrical stimulation of the LHb inhibits most DA neurons indirectly via the RMTg.
“Furthermore, electrical stimulation of the LHb inhibits the vast majority of DA neurons [69, 71, 72]. Such inhibition is not direct, but rather occurs through the stimulation of neurons in the rostromedial tegmental nucleus (RMTg) [73].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [71]
Cumulative evidence points to the habenula as one region that controls decreases in firing of dopaminergic cells in the VTA that may follow failure to receive an expected reward.
“Cumulative evidence (148–151) points to the habenula as one of the regions that controls the decreases in firing of dopaminergic cells in VTA that may follow the failure to receive an expected reward (152).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [149]
Habenula stimulation elicits inhibitory electrophysiological dopamine responses through an intermediate reticular nucleus, rather than the excitatory responses required for a postulated aversive dopamine influence on place preferences.
“In support of the latter result, habenula stimulation elicits inhibitory electrophysiological dopamine responses139–141 through an intermediate reticular nucleus138, rather than the excitatory responses required for a postulated aversive dopamine influence on place preferences137.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [139]
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- Authors
- Christoph, G., Leonzio, R., & Wilcox, K.
- Affiliations
- DuPont (United States) (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1986-03-01
- Volume
- 6
- Issue
- 3
- Pages
- 613-619
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6568453
- OpenAlex
- W1542275754
- Cited by
- 418
- References
- 21
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 16 · 2023: 8 · 2022: 18 · 2021: 21 · 2020: 19 · 2019: 12 · 2018: 23 · 2017: 20 · 2016: 27 · 2015: 23 · 2014: 17 · 2013: 26 · 2012: 22
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- lateral habenula, substantia nigra pars compacta, ventral tegmental area, fasciculus retroflexus, stria medullaris, kainic acid lesion, dopaminergic activity
- MeSH terms
- Animals, Dopamine, Electric Stimulation, Kainic Acid, Male, Neurons, Rats, Inbred Strains, Substantia Nigra, Tegmentum Mesencephali, Thalamus, Time Factors, Rats
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