Galanin is a Selective Marker of the Retrotrapezoid Nucleus in Rats

Overview

Journal J Comp Neurol

Specialty Neurology

Date 2008 Nov 14

PMID 19006184

Citations 25

Authors

Ruth L Stornetta

Darko Spirovski

Thiago S Moreira

Ana C Takakura

Gavin H West

Justin M Gwilt

Paul M Pilowsky

Patrice G Guyenet

Affiliations

Soon will be listed here.

Abstract

The rat retrotrapezoid nucleus (RTN) contains CO(2)-activated neurons that contribute to the central chemoreflex and to breathing automaticity. These neurons have two known markers, the transcription factor Phox2b and vesicular glutamate transporter 2 (VGLUT2). Noncatecholaminergic galanin-immunoreactive (ir) neurons within a region of the lower brainstem that seems identical to what is currently defined as the RTN have been previously described. Here we ask whether these galanin-expressing neurons are the same cells as the recently characterized CO(2)-sensitive neurons of the RTN. By using in situ hybridization, we found that pre-pro-galanin (PPGal) mRNA is expressed by an isolated cluster of neurons that is co-extensive with the RTN as defined by a population of strongly Phox2b-ir neurons devoid of tyrosine hydroxylase (Phox2b(+)/TH(-) neurons). This bilateral structure contains about 1,000 PPGal mRNA-positive neurons in the rat. The PPGal mRNA-positive neurons were Phox2b(+)/TH(-) and as susceptible to destruction by the toxin [Sar(9), Met (O(2))(11)]-substance P as the rest of the RTN Phox2b(+)/TH(-) cells of the RTN. CO(2)-activated neurons were recorded in the RTN of anesthetized rats and were labeled with biotinamide. Many of those cells (7/17, 41%, five rats) contained PPGal-mRNA. In conclusion, galanin mRNA is a very specific marker of the glutamatergic Phox2b(+)/TH(-) neurons of the RTN, but galanin mRNA identifies only half of these putative central respiratory chemoreceptors.

Citing Articles

Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?.

Souza G, Abbott S Respir Physiol Neurobiol. 2024; 322:104217.

PMID: 38237884 PMC: 10922619. DOI: 10.1016/j.resp.2024.104217.

Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups.

Gonye E, Bayliss D Front Physiol. 2023; 14:1241662.

PMID: 37719465 PMC: 10502317. DOI: 10.3389/fphys.2023.1241662.

Mild and moderate chronic hypercapnia elicit distinct transcriptomic responses of immune function in cardiorespiratory nuclei.

Grams K, Neumueller S, Mouradian Jr G, Burgraff N, Hodges M, Pan L Physiol Genomics. 2023; 55(11):487-503.

PMID: 37602394 PMC: 11178267. DOI: 10.1152/physiolgenomics.00038.2023.

Neuromedin B-Expressing Neurons in the Retrotrapezoid Nucleus Regulate Respiratory Homeostasis and Promote Stable Breathing in Adult Mice.

Souza G, Stornetta D, Shi Y, Lim E, Berry F, Bayliss D J Neurosci. 2023; 43(30):5501-5520.

PMID: 37290937 PMC: 10376939. DOI: 10.1523/JNEUROSCI.0386-23.2023.

Involvement of neurokinin-1 receptors in the autonomic nervous system in colorectal distension-induced cardiovascular suppression in rats.

Kurogochi K, Uechi M, Orito K Front Pharmacol. 2022; 13:1020685.

PMID: 36339556 PMC: 9627219. DOI: 10.3389/fphar.2022.1020685.

References

Hokfelt T . Galanin and its receptors: introduction to the Third International Symposium, San Diego, California, USA, 21-22 October 2004. Neuropeptides. 2005; 39(3):125-42. DOI: 10.1016/j.npep.2005.03.002. View

Llona I, Eugenin J . Central actions of somatostatin in the generation and control of breathing. Biol Res. 2006; 38(4):347-52. DOI: 10.4067/s0716-97602005000400006. View

Loeschcke H . Central chemosensitivity and the reaction theory. J Physiol. 1982; 332:1-24. PMC: 1197383. DOI: 10.1113/jphysiol.1982.sp014397. View

Mulkey D, Talley E, Stornetta R, Siegel A, West G, Chen X . TASK channels determine pH sensitivity in select respiratory neurons but do not contribute to central respiratory chemosensitivity. J Neurosci. 2007; 27(51):14049-58. PMC: 6673518. DOI: 10.1523/JNEUROSCI.4254-07.2007. View

Dubreuil V, Ramanantsoa N, Trochet D, Vaubourg V, Amiel J, Gallego J . A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons. Proc Natl Acad Sci U S A. 2008; 105(3):1067-72. PMC: 2242699. DOI: 10.1073/pnas.0709115105. View

Kang B, Chang D, Mackay D, West G, Moreira T, Takakura A . Central nervous system distribution of the transcription factor Phox2b in the adult rat. J Comp Neurol. 2007; 503(5):627-41. DOI: 10.1002/cne.21409. View

Nattie E, Li A . Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol. 2002; 544(2):603-16. PMC: 2290611. DOI: 10.1113/jphysiol.2002.020032. View

Melander T, Hokfelt T, Rokaeus A . Distribution of galaninlike immunoreactivity in the rat central nervous system. J Comp Neurol. 1986; 248(4):475-517. DOI: 10.1002/cne.902480404. View

Onimaru H, Homma I . A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J Neurosci. 2003; 23(4):1478-86. PMC: 6742245. View

10.

Guyenet P . The sympathetic control of blood pressure. Nat Rev Neurosci. 2006; 7(5):335-46. DOI: 10.1038/nrn1902. View

11.

Nattie E, Li A . Muscimol dialysis in the retrotrapezoid nucleus region inhibits breathing in the awake rat. J Appl Physiol (1985). 2000; 89(1):153-62. DOI: 10.1152/jappl.2000.89.1.153. View

12.

Schreihofer A, Stornetta R, Guyenet P . Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat. J Physiol. 2000; 529 Pt 1:221-36. PMC: 2270165. DOI: 10.1111/j.1469-7793.2000.00221.x. View

13.

Feldman J, Del Negro C . Looking for inspiration: new perspectives on respiratory rhythm. Nat Rev Neurosci. 2006; 7(3):232-42. PMC: 2819067. DOI: 10.1038/nrn1871. View

14.

Clarke P . How inaccurate is the Abercrombie correction factor for cell counts?. Trends Neurosci. 1992; 15(6):211-2. DOI: 10.1016/0166-2236(92)90036-8. View

15.

McCrimmon D, Smith J, Feldman J . Involvement of excitatory amino acids in neurotransmission of inspiratory drive to spinal respiratory motoneurons. J Neurosci. 1989; 9(6):1910-21. PMC: 6569729. View

16.

Nattie E, Li A . Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat. J Appl Physiol (1985). 2006; 101(6):1596-606. DOI: 10.1152/japplphysiol.00347.2006. View

17.

Amiel J, Laudier B, Attie-Bitach T, Trang H, De Pontual L, Gener B . Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet. 2003; 33(4):459-61. DOI: 10.1038/ng1130. View

18.

Kafitz K, Rose C, Thoenen H, Konnerth A . Neurotrophin-evoked rapid excitation through TrkB receptors. Nature. 1999; 401(6756):918-21. DOI: 10.1038/44847. View

19.

Xu Z, Zheng K, Hokfelt T . Electrophysiological studies on galanin effects in brain--progress during the last six years. Neuropeptides. 2005; 39(3):269-75. DOI: 10.1016/j.npep.2005.02.003. View

20.

Tan W, Janczewski W, Yang P, Shao X, Callaway E, Feldman J . Silencing preBötzinger complex somatostatin-expressing neurons induces persistent apnea in awake rat. Nat Neurosci. 2008; 11(5):538-40. PMC: 2515565. DOI: 10.1038/nn.2104. View