Parabrachial nuclei

The parabrachial nuclei, also known as the parabrachial complex, are a group of nuclei in the dorsolateral pons that surrounds the superior cerebellar peduncle as it enters the brainstem from the cerebellum. They are named from the Latin term for the superior cerebellar peduncle, the brachium conjunctivum. In the human brain, the expansion of the superior cerebellar peduncle expands the parabrachial nuclei, which form a thin strip of grey matter over most of the peduncle. The parabrachial nuclei are typically divided along the lines suggested by Baxter and Olszewski in humans, into a medial parabrachial nucleus and lateral parabrachial nucleus.^[1] These have in turn been subdivided into a dozen subnuclei: the superior, dorsal, ventral, internal, external and extreme lateral subnuclei; the lateral crescent and subparabrachial nucleus (Kolliker-Fuse nucleus) along the ventrolateral margin of the lateral parabrachial complex; and the medial and external medial subnuclei^[2][3]

Parabrachial nuclei
Parabrachial nucleus at N.0 3
Details
Part of	Brainstem
Parts	Medial parabrachial nucleus, lateral parabrachial nucleus, subparabrachial nucleus
Identifiers
Latin	nuclei parabrachiales
MeSH	D065823
NeuroNames	1927
NeuroLex ID	nlx_23647
TA98	A14.1.05.439
TA2	5945
FMA	84024
Anatomical terms of neuroanatomy [edit on Wikidata]

Anatomy

Structure

The main parabrachial nuclei are the medial parabrachial nucleus, the lateral parabrachial nucleus, and the subparabrachial nucleus. They are located at the junction of the midbrain and pons.^[4]

Medial parabrachial nucleus

The medial parabrachial nucleus relays information from the taste area of the solitary nucleus to the ventral posteromedial nucleus of the thalamus.^[4]

Lateral parabrachial nucleus

The lateral parabrachial nucleus receives information from the caudal solitary tract and transmits signals mainly to the medial hypothalamus but also to the lateral hypothalamus and many of the nuclei targeted by the medial parabrachial nucleus.^[4]

Subparabrachial nucleus

The subparabrachial nucleus (also known as the Kölliker-Fuse nucleus, or diffuse reticular nucleus) regulates the breathing rate. It receives signals from the caudal, cardio-respiratory part of the solitary nucleus and sends signals to the lower medulla oblongata, the spinal cord, the amygdala and the lateral hypothalamus.^[4]

Afferents and efferents

The parabrachial nuclei receive visceral afferent information from a variety of sources in the brainstem, including much from the solitary nucleus, which brings taste information and information about the remainder of the body.^[5]

The external, dorsal, internal and superior lateral subnuclei also receive input from the spinal and trigeminal dorsal horn, mainly concerned with pain and other visceral sensations.^[6]

Outputs from the parabrachial nucleus originate from specific subnuclei and target forebrain sites involved in autonomic regulation, including the lateral hypothalamic area, ventromedial, dorsomedial, and arcuate hypothalamic nuclei, the median and lateral preoptic nuclei, the substantia innominate, the ventroposterior parvicellular and intralaminar thalamic nuclei, the central nucleus of the amygdala, and the insular and infralimbic cortex.^[2]

The subparabrachialnucleus and lateral crescent send efferents to the nucleus of the solitary tract, ventrolateral medulla, and spinal cord, where they target many respiratory and autonomic cell groups.^[3] Many of these same brainstem and forebrain areas send efferents back to the parabrachial nucleus as well.^[7][5]

Function

Arousal

Further information: Ascending reticular activating system

Many subsets of neurons in the parabrachial complex that target specific forebrain or brainstem cell groups contain specific neuropeptides,^[8] and appear to carry out distinct functions. For example, a population of neurons in the external lateral parabrachial subnucleus that contain the neurotransmitter calcitonin gene-related peptide (CGRP) appears to be critical for relaying information about hypoxia (low blood oxygen) and/or hypercapnia (high blood CO₂) to forebrain sites to “wake up the brain” (arouse) when breathing is inadequate to meet physiological demands during sleep. This resulting “wakefulness drive to breath” contributes to prevention of asphyxia.^[9]

Recent data indicate that glutamatergic neurons in the medial and lateral parabrachial nuclei, along with glutamatergic neurons in the pedunculopontine tegmental nucleus, provide a critical node in the brainstem for producing a waking state.^[10][11] Lesions of these neurons cause irreversible coma.

Blood sugar control

Other neurons in the superior lateral parabrachial nucleus that contain cholecystokinin have been found to prevent hypoglycemia.^[12]

Thermoregulation

Other neurons in the dorsal lateral parabrachial nucleus that contain dynorphin sense skin temperature from spinal afferents, and send that information to neurons in the preoptic area involved in thermoregulation.^[13] A study in 2017, has shown this information to be relayed through the lateral parabrachial nucleus rather than the thalamus, which drives thermoregulatory behaviour.^[14][15]

Taste

Parabrachial neurons in rodents that relay taste information to the ventroposterior parvocellular (taste) nucleus of the thalamus are mainly CGRP neurons in the external medial parabrachial nucleus and they project predominantly contralaterally, as well as a smaller number in the ventral lateral nucleus, which project mainly ipsilaterally.^[16]

Neurons that mediate the sensation of itching, connect to the parabrachial nucleus by way of glutamatergic spinal projection neurons. This pathway triggers scratching in mice.^[17]

Pleasure

The parabrachial nucleus relays satiety and pain-related signals to higher brain regions; when inhibited, this can produce "liking" responses to certain pleasurable stimuli, such as sweet taste.^[18]

Wet dog shakes

The lateral parabrachial nucleus integrates sensory signals, primarily, but not exclusively, from low-threshold mechanoreceptors to initiate the wet dog shake behavior by which mammals remove water and irritants from their back and neck fur. It receives this mechanoreceptor input from group C nerve fibers that connect to spinoparabrachial neurons in the spinal cord.^[19]

References

1. Olszewski, J (1954). Cytoarchitecture of the Human Brainstem. Lippincott. pp. 1–199.
2. Fulwiler, C. E.; Saper, C. B. (1984-08-01). "Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat". Brain Research. 319 (3): 229–259. doi:10.1016/0165-0173(84)90012-2. ISSN 0006-8993. PMID 6478256. S2CID 13253760.
3. Yokota, Shigefumi; Kaur, Satvinder; VanderHorst, Veronique G.; Saper, Clifford B.; Chamberlin, Nancy L. (2015-04-15). "Respiratory-related outputs of glutamatergic, hypercapnia-responsive parabrachial neurons in mice". The Journal of Comparative Neurology. 523 (6): 907–920. doi:10.1002/cne.23720. ISSN 1096-9861. PMC 4329052. PMID 25424719.
4. Thomas P. Naidich; Henri M. Duvernoy; Bradley N. Delman (1 January 2009). Duvernoy's Atlas of the Human Brain Stem and Cerebellum: High-field MRI : Surface Anatomy, Internal Structure, Vascularization and 3D Sectional Anatomy. Springer. p. 324. ISBN 978-3-211-73971-6.
5. Herbert, H.; Moga, M. M.; Saper, C. B. (1990-03-22). "Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat". The Journal of Comparative Neurology. 293 (4): 540–580. doi:10.1002/cne.902930404. ISSN 0021-9967. PMID 1691748. S2CID 26878489.
6. Cechetto, D. F.; Standaert, D. G.; Saper, C. B. (1985-10-08). "Spinal and trigeminal dorsal horn projections to the parabrachial nucleus in the rat". The Journal of Comparative Neurology. 240 (2): 153–160. doi:10.1002/cne.902400205. ISSN 0021-9967. PMID 3840498. S2CID 36330716.
7. Moga, M. M.; Herbert, H.; Hurley, K. M.; Yasui, Y.; Gray, T. S.; Saper, C. B. (1990-05-22). "Organization of cortical, basal forebrain, and hypothalamic afferents to the parabrachial nucleus in the rat". The Journal of Comparative Neurology. 295 (4): 624–661. doi:10.1002/cne.902950408. ISSN 0021-9967. PMID 1694187. S2CID 41283776.
8. Block, C. H.; Hoffman, G. E. (1987-03-01). "Neuropeptide and monoamine components of the parabrachial pontine complex". Peptides. 8 (2): 267–283. doi:10.1016/0196-9781(87)90102-1. ISSN 0196-9781. PMID 2884646. S2CID 23357848.
9. Kaur, Satvinder; Pedersen, Nigel P.; Yokota, Shigefumi; Hur, Elizabeth E.; Fuller, Patrick M.; Lazarus, Michael; Chamberlin, Nancy L.; Saper, Clifford B. (2013-05-01). "Glutamatergic signaling from the parabrachial nucleus plays a critical role in hypercapnic arousal". The Journal of Neuroscience. 33 (18): 7627–7640. doi:10.1523/JNEUROSCI.0173-13.2013. ISSN 1529-2401. PMC 3674488. PMID 23637157.
10. Fuller, Patrick M.; Fuller, Patrick; Sherman, David; Pedersen, Nigel P.; Saper, Clifford B.; Lu, Jun (2011-04-01). "Reassessment of the structural basis of the ascending arousal system". The Journal of Comparative Neurology. 519 (5): 933–956. doi:10.1002/cne.22559. ISSN 1096-9861. PMC 3119596. PMID 21280045.
11. Kroeger, Daniel; Ferrari, Loris L.; Petit, Gaetan; Mahoney, Carrie E.; Fuller, Patrick M.; Arrigoni, Elda; Scammell, Thomas E. (2017-02-01). "Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice". The Journal of Neuroscience. 37 (5): 1352–1366. doi:10.1523/JNEUROSCI.1405-16.2016. ISSN 1529-2401. PMC 5296799. PMID 28039375.
12. Garfield, Alastair S.; Shah, Bhavik P.; Madara, Joseph C.; Burke, Luke K.; Patterson, Christa M.; Flak, Jonathan; Neve, Rachael L.; Evans, Mark L.; Lowell, Bradford B. (2014-12-02). "A parabrachial-hypothalamic cholecystokinin neurocircuit controls counterregulatory responses to hypoglycemia". Cell Metabolism. 20 (6): 1030–1037. doi:10.1016/j.cmet.2014.11.006. ISSN 1932-7420. PMC 4261079. PMID 25470549.
13. Geerling, Joel C.; Kim, Minjee; Mahoney, Carrie E.; Abbott, Stephen B. G.; Agostinelli, Lindsay J.; Garfield, Alastair S.; Krashes, Michael J.; Lowell, Bradford B.; Scammell, Thomas E. (2016-01-01). "Genetic identity of thermosensory relay neurons in the lateral parabrachial nucleus". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 310 (1): R41–54. doi:10.1152/ajpregu.00094.2015. ISSN 1522-1490. PMC 4747895. PMID 26491097.
14. Nakamura, K (2018). "Thermoregulatory behavior and its central circuit mechanism-What thermosensory pathway drives it?]". Clinical Calcium. 28 (1): 65–72. PMID 29279428.
15. Yahiro, T; Kataoka, N; Nakamura, Y; Nakamura, K (10 July 2017). "The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory pathways for behavioural thermoregulation". Scientific Reports. 7 (1): 5031. Bibcode:2017NatSR...7.5031Y. doi:10.1038/s41598-017-05327-8. PMC 5503995. PMID 28694517.
16. Yasui, Y.; Saper, C. B.; Cechetto, D. F. (1989-12-22). "Calcitonin gene-related peptide immunoreactivity in the visceral sensory cortex, thalamus, and related pathways in the rat". The Journal of Comparative Neurology. 290 (4): 487–501. doi:10.1002/cne.902900404. ISSN 0021-9967. PMID 2613940. S2CID 28112065.
17. Mu, Di; Deng, Juan; Liu, Ke-Fei; Wu, Zhen-Yu; Shi, Yu-Feng; Guo, Wei-Min; Mao, Qun-Quan; Liu, Xing-Jun; Li, Hui; Sun, Yan-Gang (17 August 2017). "A central neural circuit for itch sensation". Science. 357 (6352): 695–699. Bibcode:2017Sci...357..695M. doi:10.1126/science.aaf4918. PMID 28818946.
18. Berridge KC, Kringelbach ML (May 2015). "Pleasure systems in the brain". Neuron. 86 (3): 646–664. doi:10.1016/j.neuron.2015.02.018. PMC 4425246. PMID 25950633. In the prefrontal cortex, recent evidence indicates that the OFC and insula cortex may each contain their own additional hot spots (D.C. Castro et al., Soc. Neurosci., abstract). In specific subregions of each area, either opioid-stimulating or orexin-stimulating microinjections appear to enhance the number of liking reactions elicited by sweetness, similar to the NAc and VP hot spots. Successful confirmation of hedonic hot spots in the OFC or insula would be important and possibly relevant to the orbitofrontal mid-anterior site mentioned earlier that especially tracks the subjective pleasure of foods in humans (Georgiadis et al., 2012; Kringelbach, 2005; Kringelbach et al., 2003; Small et al., 2001; Veldhuizen et al., 2010). Finally, in the brainstem, a hindbrain site near the parabrachial nucleus of dorsal pons also appears able to contribute to hedonic gains of function (So¨ derpalm and Berridge, 2000). A brainstem mechanism for pleasure may seem more surprising than forebrain hot spots to anyone who views the brainstem as merely reflexive, but the pontine parabrachial nucleus contributes to taste, pain, and many visceral sensations from the body and has also been suggested to play an important role in motivation (Wu et al., 2012) and in human emotion (especially related to the somatic marker hypothesis) (Damasio, 2010).
19. Zhang, Dawei; Turecek, Josef; Choi, Seungwon; Delisle, Michelle; Pamplona, Caroline Leal; Meltzer, Shan; Ginty, David D. (2024). "C-LTMRs evoke wet dog shakes via the spinoparabrachial pathway". Science. 386 (6722): 686–692. doi:10.1126/science.adq8834. ISSN 0036-8075.