Neurochemical organization of the nucleus paramedianus dorsalis in the human

Abstract

We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (antibody SMI-32). In transverse sections, PMD is oval with its long axis aligned with the dorsal border of the brainstem. We identified PMD in eight human brainstems, but found some variability both in its cross-sectional area and in its A-P extent among cases. It includes calretinin immunoreactive large cells with oval or polygonal cell bodies. Cells in PMD are not immunoreactive for either calbindin or parvalbumin, but a few fibers immunoreactive to each protein are found within its central region. Cells in PMD are also immunoreactive to nNOS, and immunoreactivity to a neurofilament protein shows many labeled cells and fibers. No similar region is identified in atlases of the cat, mouse, rat or monkey brain, nor does immunoreactivity to any of the markers that delineate it in the human reveal a comparable region in those species. The territory that PMD occupies is included in PH in other species. Since anatomical and physiological data in animals suggest that PH may have multiple subregions, we suggest that the PMD in human may be a further differentiation of PH and may have functions related to the vestibular control of eye movements.

Figure 1

The organization of the human medulla at the caudal (A) and rostral (B) limits of the nucleus paramedianus (arrows). The two sections are about 4 mm apart. Adapted from plates drawn from Nissl sections in the atlas of Olszewski and Baxter (1954). Abbreviations: Am, nucleus ambiguus; Arc, nucleus arcuatus; Cor. po, Nucleus corporis pontobulbaris; Co. v, Nucleus cochlearis ventralis; Cu .l, nucleus cuneatus lateralis; D. mo. X, Nucleus dorsalis motorius nervi vagi; Gc, nucleus gigantocellularis; Ipo, Nucleus interpositus; Le. m, lemniscus medialis; N VII, Nucleus nervi facialis; Ol. i. d, Nucleus olivaris inferior accessorius dorsalis; Ol. i. m Nucleus olivaris inferior accessorius medialis; Ol. i. pr, Nucleus olivaris inferior principalis; Ov, Nucleus ovalis; Pc, nucleus parvocellularis; Pe. ce. i, Pedunculus cerebelli inferior; Pg. d, Nucleus paragigantocellularis dorsalis; Pg. l, Nucleus paragigantocellularis lateralis; Pm. c, Nucleus paramedianus dorsalis caudalis; Pm. o, Nucleus paramedianus dorsalis oralis; Prp, Nucleus prepositus hypoglossi; Pyr, pyramis; Ra. ob, Nucleus raphae obscurus; Ra. pa, Nucleus raphae pallidus; Sol, Nucleus tractus solitarii; Sp. V. o, Nucleus tractus spinalis trigemini oralis; St. gl, Stratum gliosum subependymale; Sub, Nucleus medullae oblongatae subtrigeminalis; T. sol, Tractus solitarius; T. sp. V, Tractus nervi trigemini spinalis; VIII. m, Nucleus vestibularis medialis; VIII. sp, Nucleus vestibularis spinalis; α Islands of cells that resemble cells on the pontine gray.

Figure 2

The nucleus paramedianus dorsalis (PMD), Nissl staining, transverse section. The A-P extent of the nucleus in this case is about 5 mm. The section shown is about 2 mm rostral to the caudal pole of PMD. A. The arrows indicate PMD, which is seen as a darkly stained oval region lying just medial to the nucleus prepositus hypoglossi (PH), lateral to the midline and dorsal to the reticular formation (RF). Scale bar 1 mm. B. PMD consists of cells with large irregularly shaped somas; examples at arrows. Abbreviations: CV, cresyl violet; RF, reticular formation. Scale bar 100 μm. Case180, m, age 54.

Figure 3

Immunoreactivity to calretinin in PMD on a section at the same level as in Fig. 1. A. The arrow shows PMD, which is darkly stained in contrast to PH laterally and the midline reticular formation. Scale bar 1 mm. B. Calretinin immunoreactive cells in PMD (arrows) have oval or polygonal cell bodies. Abbreviation: CR, calretinin. Scale bar 100 μm.

Figure 4

Immunoreactivity to calbindin in PMD; section about 200 μm rostral to the one in Fig. 3. A. PMD is lightly stained and is located just dorsal to a darkly stained patch of cells and fibers in the reticular formation (black arrowhead). There are several darkly stained patches (arrows) more laterally. The asterisk is an alignment point. Scale bar 1 mm. B. Immunoreactive fine varicose fibers in the central part of PMD. The asterisk is at the same position as in A. Scale bar 100 μm. C. Higher magnification image of the calbindin immunoreactive varicose processes in the center of PMD. Abbreviations: CB, calbindin. Scale bar 50 μm.

Figure 5

Parvalbumin immunoreactivity in PMD. The section is about 1 mm rostral to the posterior pole of PMD. A. The arrow points to PMD which is seen as a white oval with some staining in the center. The arrowheads point to darker patches of parvalbumin immunoreactivity laterally in the dorsal brainstem. Scale bar 1 mm. B. Higher magnification view of the fiber staining in the center of PMD. The arrow indicates one immunoreactive fiber. Abbreviation: PV, parvalbumin. Scale bar 100 μm.

Figure 6

Nitric oxide synthase (nNOS) immunoreactivity in PMD. A. PMD is a darkly stained oval, and is the most darkly stained structure in the dorsal brainstem. The arrowheads show the approximate medial and lateral borders of PH, in which stained cells are also seen. Scale bar 1 mm. B. Darkly stained cells (arrows) and neuropil in PMD. The arrowheads indicate stained cells in PH. Scale bar 100 μm. The A-P extent of PMD is about 6 mm. The section illustrated is about 200 μm rostral to its posterior pole. Case 176, f, age 71.

Figure 7

Immunoreactivity to a nonphosphorylated neurofilament protein in PMD on a section close to the caudal pole. A. Arrow shows the location of PMD, a dark oval. Scale bar 1 mm. B. Higher magnification image of PMD; arrows indicate its borders. The asterisk is an alignment point for C. Scale bar 100 μm. C. Stained fibers in PMD (examples at arrows) running in all directions on a background of darkly-stained neuropil. Asterisk as in B. Abbreviation: SMI-32, antibody to neurofilament protein. Scale bar 50 μm.

Figure 8

Variability of the size and shape of PMD in four cases. The sections are at about the A-P center of PMD. Case 168, m, age 69, A-P extent of PMD about 6 mm. Case 166, f, age 75. A-P extent about 5 mm. Case 169, m, age 70, A-P extent about 7 mm. Case 164, f, age 45; A-P extent about 8 mm. Scale bar (for all panels) 250 μm.