Abstract
The arcuate nucleus (Arc) of the medulla is found in almost all human brains and in a small percentage of chimpanzee brains. It is absent in the brains of other mammalian species including mice, rats, cats, and macaque monkeys. The Arc is classically considered a precerebellar relay nucleus, receiving input from the cerebral cortex and projecting to the cerebellum via the inferior cerebellar peduncle. However, several studies have found aplasia of the Arc in babies who died of SIDS (Sudden Infant Death Syndrome), and it was suggested that the Arc is the locus of chemosensory neurons critical for brainstem control of respiration. Aplasia of the Arc, however, has also been reported in adults, suggesting that it is not critical for survival. We have examined the Arc in closely spaced Nissl-stained sections in thirteen adult human cases to acquire a better understanding of the degree of variability of its size and location in adults. We have also examined immunostained sections to look for neurochemical compartments in this nucleus. Caudally, neurons of the Arc are ventrolateral to the pyramidal tracts (py); rostrally, they are ventro-medial to the py and extend up along the midline. In some cases, the Arc is discontinuous, with a gap between sections with the ventrolaterally located and the ventromedially located neurons. In all cases, there is some degree of left-right asymmetry in Arc position, size, and shape at all rostro-caudal levels. Somata of neurons in the Arc express calretinin (CR), neuronal nitric oxide synthase (nNOS), and nonphosphorylated neurofilament protein (NPNFP). Calbindin (CB) is expressed in puncta whereas there is no expression of parvalbumin (PV) in somata or puncta. There is also immunostaining for GAD and GABA receptors suggesting inhibitory input to Arc neurons. These properties were consistent among cases. Our data show differences in location of caudal and rostral Arc neurons and considerable variability among cases in the size and shape of the Arc. The variability in size suggests that "hypoplasia" of the Arc is difficult to define. The discontinuity of the Arc in many cases suggests that establishing aplasia of the Arc requires examination of many closely spaced sections through the brainstem.
Highlights
The arcuate nucleus of the medulla (Arc) is a prominent structure in the human brainstem (Olszewski and Baxter 1982; Mikhail and Ahmed 1975; Essick 1912)
A totally different view of the Arc has been proposed on the basis of neuropathological observations showing aplasia of the Arc in the brains of children who died of SIDS
The caudal subdivision consists of neurons located ventrolaterally to the py whereas the rostral Arc is found ventromedially to the py with neurons extending up the midline
Summary
The arcuate nucleus of the medulla (Arc) is a prominent structure in the human brainstem (Olszewski and Baxter 1982; Mikhail and Ahmed 1975; Essick 1912). A totally different view of the Arc has been proposed on the basis of neuropathological observations showing aplasia of the Arc in the brains of children who died of SIDS Another term for the same syndrome is Sudden Unexpected Death in Infancy, SUDI. We will use the term SIDS to include all cases of sudden unexpected death, both prenatal and postnatal) Such cases are described in many studies (Filiano and Kinney 1992; Kinney et al 1992; Matturri et al 2000; Filiano and Kinney 1995, 1994; Kinney and Filiano 1988; Franciosi and Segura 2004; Biondo et al 2003; Folgering et al 1979). The interpretation of these observations was that the Arc is the site of chemosensitive neurons that are critical for respiration and survival (Filiano et al 1990)
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