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The mesopontine rostromedial tegmental nucleus: A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta
Open accessAbstract
Prior studies revealed that aversive stimuli and psychostimulant drugs elicit Fos expression in neurons clustered above and behind the interpeduncular nucleus that project strongly to the ventral tegmental area (VTA) and substantia nigra (SN) compacta (C). Other reports suggest that these neurons modulate responses to aversive stimuli. We now designate the region containing them as the "mesopontine rostromedial tegmental nucleus" (RMTg) and report herein on its neuroanatomy. Dense micro-opioid receptor and somatostatin immunoreactivity characterize the RMTg, as do neurons projecting to the VTA/SNC that are enriched in GAD67 mRNA. Strong inputs to the RMTg arise in the lateral habenula (LHb) and, to a lesser extent, the SN. Other inputs come from the frontal cortex, ventral striatopallidum, extended amygdala, septum, preoptic region, lateral, paraventricular and posterior hypothalamus, zona incerta, periaqueductal gray, intermediate layers of the contralateral superior colliculus, dorsal raphe, mesencephalic, pontine and medullary reticular formation, and the following nuclei: parafascicular, supramammillary, mammillary, ventral lateral geniculate, deep mesencephalic, red, pedunculopontine and laterodorsal tegmental, cuneiform, parabrachial, and deep cerebellar. The RMTg has meager outputs to the forebrain, mainly to the ventral pallidum, preoptic-lateral hypothalamic continuum, and midline-intralaminar thalamus, but much heavier outputs to the brainstem, including, most prominently, the VTA/SNC, as noted above, and to medial tegmentum, pedunculopontine and laterodorsal tegmental nuclei, dorsal raphe, and locus ceruleus and subceruleus. The RMTg may integrate multiple forebrain and brainstem inputs in relation to a dominant LHb input. Its outputs to neuromodulatory projection systems likely converge with direct LHb projections to those structures.
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“It was shown that the LHb has an inhibitory influence on dopaminergic neurons (Matsumoto and Hikosaka, 2007) via GABAergic interneurons in the rostromedial tegmental nucleus (Ji and Shepard, 2007; Jhou et al., 2009), which is reflected by the fact that lesioning of the habenula leads to an increase of cortical and striatal dopamine levels (Nishikawa et al., 1986).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Jhou et al., 2009
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Dopamine in motivational control: rewarding, aversive, and alerting
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.022 · Cited by 2,396
Input-specific control of reward and aversion in the ventral tegmental area
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Hikosaka, O. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2866 · Cited by 955
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Metadata
- Authors
- Jhou, T. C., Geisler, S., Marinelli, M., Degarmo, B. A., & Zahm, D. S.
- Affiliations
- National Institutes of Health (US)
- Saint Louis University (US)
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Jhou, Thomas C.
- Zahm, Daniel S.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2009-02-20
- Volume
- 513
- Issue
- 6
- Pages
- 566-596
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC3116663
- OpenAlex
- W2085520758
- Cited by
- 503
- References
- 102
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 35 · 2023: 13 · 2022: 17 · 2021: 39 · 2020: 48 · 2019: 39 · 2018: 34 · 2017: 27 · 2016: 34 · 2015: 26 · 2014: 38 · 2013: 36 · 2012: 28
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 60292, P50HL060292)
- National Institute of Mental Health (MH-12370, F31MH012370)
- National Institute on Drug Abuse (DA020654, R01DA020654)
- National Institute of Neurological Disorders and Stroke (NS23805, R01NS023805)
- 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 › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- rostromedial tegmental nucleus, lateral habenula, ventral tegmental area, substantia nigra pars compacta, mesopontine tegmentum, interpeduncular nucleus, Fos expression, aversive stimuli, psychostimulants, mu-opioid receptor, somatostatin, GAD67, neuroanatomy, brainstem projections, neuromodulation, pedunculopontine nucleus, laterodorsal tegmentum, dorsal raphe nucleus, locus coeruleus
- MeSH terms
- Animals, Cocaine, Glutamate Decarboxylase, Male, Methamphetamine, Neural Pathways, RNA, Messenger, Self Administration, Somatostatin, Substantia Nigra, Sulfur Radioisotopes, Tegmentum Mesencephali, Gene Expression, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Receptors, Opioid, mu, Ventral Tegmental Area, Habenula, Rats
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