Dopaminergic input to GABAergic neurons in the rostral agranular insular cortex of the rat
Abstract
Increasing evidence shows that the rostral agranular insular cortex (RAIC) is important in the modulation of nociception in humans and rats and that dopamine and GABA appear to be key neurotransmitters in the function of this cortical region. Here we use immunocytochemistry and path tracing to examine the relationship between dopamine and GABA related elements in the RAIC of the rat. We found that the RAIC has a high density of dopamine fibers that arise principally from the ipsilateral ventral tegmental area/substantia nigra (VTA/SN) and from a different set of neurons than those that project to the medial prefrontal cortex. Within the RAIC, there are close appositions between dopamine fibers and GABAergic interneurons. One target of cortical GABA appears to be a dense band of GABAB receptor-bearing neurons located in lamina 5 of the RAIC. The GABAB receptor-bearing neurons project principally to the amygdala and nucleus accumbens with few or no projections to the medial prefrontal cortex, cingulate gyrus, the mediodorsal thalamic nucleus or contralateral RAIC. The current anatomical data, together with previous behavioral results, suggest that part of the dopaminergic modulation of the RAIC occurs through GABAergic interneurons. GABA is able to exert specific effects through its action on GABAB receptor-bearing projection neurons that target a few subcortical limbic structures. Through these connections, dopamine innervation of the RAIC is likely to affect the motivational and affective dimensions of pain.
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Insular cortex is interconnected with the SDMN; this connectivity includes inputs from the hypothalamus and ventral tegmental area, reciprocal connections with the amygdala and outputs to periaqueductal gray, bed nucleus of the stria terminalis, nucleus accumbens, and medial prefrontal cortex.
“Importantly, insular cortex is interconnected with the SDMN; this connectivity includes inputs from the hypothalamus11 and ventral tegmental area12, reciprocal connections with the amygdala13 and outputs to periaqueductal gray14, bed nucleus of the stria terminalis, nucleus accumbens15, and medial prefrontal cortex16.”
From Insular cortex mediates approach and avoidance responses to social affective stimuli (2018) · cites this paper as [12]
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- Authors
- Ohara, P. T., Granato, A., Moallem, T. M., Wang, B.-R., Tillet, Y., & Jasmin, L.
- Affiliations
- University of California, San Francisco (US)
- Università Cattolica del Sacro Cuore (IT)
- Air Force Medical University (CN)
- Centre National de la Recherche Scientifique (FR)
- Venue
- Journal of Neurocytology
- Published
- 2003-02
- Volume
- 32
- Issue
- 2
- Pages
- 131-141
- ISSN
- 0300-4864 (ISSN-L)
- 1573-7381
- OpenAlex
- W2031678730
- Cited by
- 111
- References
- 87
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Neurocytology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health (5r01ns039320-04)
- University of California, San Francisco
- National Institute of Neurological Disorders and Stroke (R01 NS39320)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dopaminergic innervation, GABAergic interneurons, GABAB receptors, ventral tegmental area, substantia nigra, nociception, pain modulation, amygdala, nucleus accumbens, medial prefrontal cortex, limbic system
- MeSH terms
- Animals, Benzofurans, Cerebral Cortex, Dopamine, gamma-Aminobutyric Acid, Immunohistochemistry, Interneurons, Limbic System, Male, Neural Inhibition, Neural Pathways, Synaptic Transmission, Pain, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, Ventral Tegmental Area, Presynaptic Terminals, Receptors, GABA-B, Rats
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