The arcuate nucleus is a prominent cell group in the human hindbrain, characterized by its position on the pial surface of the pyramid. It is considered to be a precerebellar nucleus and has been implicated in the pathology of several disorders of respiration. An arcuate nucleus has not been convincingly demonstrated in other mammals, but we have found a similarly positioned nucleus in the C57BL/6J mouse. The mouse arcuate nucleus consists of a variable group of neurons lying on the pial surface of the pyramid. The nucleus is continuous with the ventrolateral part of the principal nucleus of the inferior olive and both groups are calbindin positive. At first we thought that this mouse nucleus was homologous with the human arcuate nucleus, but we have discovered that the neurons of the human nucleus are calbindin negative, and are therefore not olivary in nature. We have compared the mouse arcuate neurons with those of the inferior olive in terms of molecular markers and cerebellar projection. The neurons of the arcuate nucleus and of the inferior olive share three major characteristics: they both contain neurons utilizing glutamate, serotonin or acetylcholine as neurotransmitters; they both project to the contralateral cerebellum, and they both express a number of genes not present in the major mossy fiber issuing precerebellar nuclei. Most importantly, both cell groups express calbindin in an area of the ventral hindbrain almost completely devoid of calbindin-positive cells. We conclude that the neurons of the hindbrain mouse arcuate nucleus are a displaced part of the inferior olive, possibly separated by the caudal growth of the pyramidal tract during development. The arcuate nucleus reported in the C57BL/6J mouse can therefore be regarded as a subgroup of the rostral inferior olive, closely allied with the ventral tier of the principal nucleus.

1.
Ahlsen G (1981): Retrograde labelling of retinogeniculate neurones in the cat by HRP uptake from the diffuse injection zone. Brain Res 223:374–380.
2.
Benarroch EE (2007): Brainstem respiratory control: substrates of respiratory failure of multiple system atrophy. Mov Disord 22:155–161.
3.
Benarroch EE, Schmeichel AM, Low PA, Parisi JE (2007): Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy. Brain 130:469–475.
4.
Berman AL (1968): The Brain Stem of the Cat: A Cytoarchitectonic Atlas with Stereotaxic Coordinates. Madison, University of Wisconsin Press.
5.
Bloch-Gallego E, Causeret F, Ezan F, Backer S, Hidalgo-Sanáhez M (2005): Development of precerebellar nuclei: instructive factors and intracellular mediators in neuronal migration, survival and axon pathfinding. Brain Res Brain Res Rev 49:253–266.
6.
Brodal A (1981): Neurological Anatomy in Relation to Clinical Medicine. New York, Oxford University Press.
7.
Chen ML, Witmans MB, Tablizo MA, Jubran RF, Turkel SB, Tavaré CJ, Keens TG: (2005): Disordered respiratory control in children with partial cerebellar resections. Pediatr Pulmonol 40:88–91.
8.
de Kort EJ, Gribnau AA, van Aanholt HT, Nieuwenhuys R (1985): On the development of the pyramidal tract in the rat. I. The morphology of the growth zone. Anat Embryol (Berl) 172:195–204.
9.
Ellenberger C Jr, Hanaway J, Netsky MG (1969): Embryogenesis of the inferior olivary nucleus in the rat: a radioautographic study and a re-evaluation of the rhombic lip. J Comp Neurol 137:71–79.
10.
Essick CR (1912): The development of the nuclei pontis and the nucleus arcuatus in man. Am J Anat 13:25–54.
11.
Filiano JJ, Choi JC, Kinney HC (1990): Candidate cell populations for respiratory chemosensitive fields in the human infant medulla. J Comp Neurol 293:448–465.
12.
Filiano JJ, Kinney HC (1992): Arcuate nucleus hypoplasia in the sudden infant death syndrome. J Neuropathol Exp Neurol 51:394–403.
[PubMed]
13.
Folgering H, Kuyper F, Kille JF (1979): Primary alveolar hypoventilation (Ondine’s curse syndrome) in an infant without external arcuate nucleus. Case report. Bull Eur Physiopathol Respir 15:659–665.
14.
Folkerth RD, Zanoni S, Andiman SE, Billiards SS (2008): Neuronal cell death in the arcuate nucleus of the medulla oblongata in stillbirth. Int J Dev Neurosci 26:133–140.
15.
Franklin KBJ, Paxinos G (2008): The Mouse Brain in Stereotaxic Coordinates. San Diego, Elsevier Academic Press.
16.
Fu Y, Tvrdik P, Makki N, Paxinos G, Watson C (2011): Precerebellar cell groups in the hindbrain of the mouse defined by retrograde tracing and correlated with cumulative Wnt1-Cre genetic labeling. Cerebellum 10:570–584.
17.
Gianino S, Stein SA, Li H, Lu X, Biesiada E, Ulas J, Xu XM (1999): Postnatal growth of corticospinal axons in the spinal cord of developing mice. Brain Res Dev Brain Res 112:189–204.
18.
Goffinet AM (1983): The embryonic development of the inferior olivary complex in normal and reeler (rlORL) mutant mice. J Comp Neurol 219:10–24.
19.
González de Dios J, García-Alix A, Cabañas F, Quero J, Moya M (1995): Cerebellar hypoplasia in the newborn: association with respiratory control disorders and mental retardation. Rev Neurol 23:1041–1046.
20.
Gozal D, Hathout GM, Kirlew KA, Tang H, Woo MS, Zhang J, Lufkin RB, Harper RM (1994): Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging. J Appl Physiol 76:2076–2083.
21.
Harkmark W (1954): Cell migrations from the rhombic lip to the inferior olive, the nucleus raphe and the pons: a morphological and experimental investigation on chick embryos. J Comp Neurol 100:115–209.
22.
Kinney HC, Belliveau RA, Trachtenberg FL, Rava LA, Paterson DS (2007): The development of the medullary serotonergic system in early human life. Auton Neurosci 132:81–102.
23.
Kinney HC, Filiano JJ, Sleeper LA, Mandell F, Valdes-Dapena M, White WF (1995): Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome. Science 269:1446–1450.
24.
Matturri L, Minoli I, Lavezzi AM, Cappellini A, Ramos S, Rossi L (2002): Hypoplasia of medullary arcuate nucleus in unexpected late fetal death (stillborn infants): a pathologic study. Pediatrics 109:E43.
25.
Mesulam MM (1978): Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction product with superior sensitivity for visualizing neural afferents and efferents. J Histochem Cytochem 26:106–117.
[PubMed]
26.
Mikhail Y, Ahmed YY (1975): Outline of the arcuate nucleus in the human medulla oblongata. Acta Anat (Basel) 92:285–291.
27.
Nagao S, Kitamura T, Nakamura N, Hiramatsu T, Yamada J (1997): Differences of the primate flocculus and ventral paraflocculus in the mossy and climbing fiber input organization. J Comp Neurol 382:480–498.
28.
Natti E (1991): Central respiratory chemoreceptors; in Haddad G, Farber J (eds): Developmental Neurobiology of Breathing. New York, Dekker, pp 341–372.
29.
Paterson DS, Thompson EG, Kinney HC (2006a): Serotonergic and glutamatergic neurons at the ventral medullary surface of the human infant: observations relevant to central chemosensitivity in early human life. Auton Neurosci 124:112–124.
30.
Paterson DS, Trachtenberg FL, Thompson EG, Belliveau RA, Beggs AH, et al. (2006b): Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. JAMA 296:2124–2132.
31.
Paxinos G, Halliday G, Watson C, Koutcherov Y, Wang HQ (2007): Atlas of the Developing Mouse Brain at E17.5, P0, and P6. Burlington, Academic Press.
32.
Paxinos G, Huang XF (1995): Atlas of the Human Brainstem: San Diego, Academic Press.
33.
Paxinos G, Petrides M, Watson C (2011): The Rhesus Monkey Brain in Stereotaxic Coordinates. Amsterdam, Elsevier, in press.
34.
Paxinos G, Watson C (2007): The Rat Brain in Stereotaxic Coordinates. London, Academic Press.
35.
Paxinos G, Watson C, Carrive P, Kirkcaldie M, Ashwell KW (2009): Chemoarchitectonic Atlas of the Rat Brain. San Diego, Academic Press.
36.
Paxinos G, Watson C, Petrides M, Rosa M, Tokuno H (2012): The Marmoset Brain in Stereotaxic Coordinates. San Diego, Elsevier Academic Press.
37.
Rodriguez CI, Dymecki SM (2000): Origin of the precerebellar system. Neuron 27:475–486.
38.
Rünker AE, Little GE, Suto F, Fujisawa H, Mitchell KJ (2008): Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points. Neural Dev 3:34.
39.
Scotti AL (1995): Calbindin D28k in the olivocerebellar projection: a light and electron microscope study. J Anat 187(Pt 3):649–659.
40.
Servais L, Bearzatto B, Schwaller B, Dumont M, De Saedeleer C, et al. (2005): Mono- and dual-frequency fast cerebellar oscillation in mice lacking parvalbumin and/or calbindin D-28k. Eur J Neurosci 22:861–870.
[PubMed]
41.
Snider RS, Niemer WT (1961): A Stereotaxic Atlas of the Cat Brain. Chicago, University of Chicago Press.
42.
Tomycz ND, Haynes RL, Schmidt EF, Ackerson K, Kinney HC (2010): Novel neuropathologic findings in the Haddad syndrome. Acta Neuropathol 119:261–269.
43.
Watson C, Paxinos G (2010): Chemoarchitectonic Atlas of the Mouse Brain. San Diego, Academic Press.
44.
Zec N, Filiano JJ, Kinney HC (1997): Anatomic relationships of the human arcuate nucleus of the medulla: a DiI-labeling study. J Neuropathol Exp Neurol 56:509–522.
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