The Cochlear Nuclei in Man JEAN KAVANAGH MOORE AND KIRSTEN KJELSBERG OSEN Department of Neurosciences, University of California, Sun Diego, La Jolla, Californra 92093, U S A . , and Anatomical Institute, University of Oslo, Oslo, Norway

ABSTRACT The human cochlear nuclei are composed of a ventral and a dorsal nucleus which are similar, though not identical, in their cytoarchitecture to those of other mammals. The ventral cochlear nucleus (VCN) consists of a rostral area of spherical cells, a central area of multipolar and globular cells, a posterior area of octopus cells, and a laterodorsal cap of small neurons. The interareal boundaries are less distinct in man than in the cat. The central region of multipolar cells and the cap area of small cells constitute the bulk of the human VCN. The spherical, globular, and octopus cells appear relatively less numerous in man than in other mammals. The dorsal cochlear nucleus (DCN) in man is relatively large, but lacks the typical stratification seen in other mammals, with only vestiges of the granular and molecular layers remaining. Virtually the entire DCN consists of an area of cochlear fiber neuropil containing pyramidal cells, small neurons, and occasional giant cells. The pyramidal cells have lost their typical radial orientation and lie scattered within the cochlear neuropil. Thus the entire human DCN may be equivalent to layers 2 and 3 of this nucleus in other mammals. In spite of the relatively large DCN, the acoustic striae appear small. This is in contrast to the large trapezoid body leaving the VCN. Intrinsic and descending fiber pathways to the cochlear nuclei are not clearly defined and may be less prominent in man than in the cat. The organization of the cochlear nuclei has been analyzed in detail in rodents and carnivores (Ramon y Cajal, '09; Fuse, '13; Lorente de No, '33,'76; Harrison and Warr, '62; Harrison and Irving, '65, '66a,b; Pirsig, '68; Webster et al., '68; Osen, '69; Brawer et al., '74). In primates, and particularly in man, the available studies have been less extensive (Fuse, '13; Hall, '65; Moskowitz, '69; Konigsmark, '69, '73a,b; Dublin, '74, '76). For this reason the present study was undertaken to provide a detailed description of the anatomy of the human cochlear nuclei. The purpose of the study was to establish the cytoarchitecture, i.e., the organization of the cell groups in the nuclei, and the relationship of these cell groups to the afferent and efferent connections of the complex. The intent of the study was to provide a sufficient understanding of the human cochlear nuclei to allow comparison with the same nuclei in species in which their anatomy and physiology have been studied exhaustively. Such a comparison should provide a more firm foundation for unAM. J. ANAT. (1979)154: 393-418.

derstanding the function of the human auditory system and for judging to what extent theories based on experimental anatomical and electrophysiological studies in laboratory animals may be applicable to man. MATERIALS AND METHODS

This study is based on 14 blocks of postmortem human brainstem, each containing one complete cochlear nuclear complex. In the human brain, the rostral end of the cochlear nuclei is rotated outward, forming an angle of 30"-35" between the rostrocaudal axis of the complex and the neuraxis, rather than lying parallel to i t as in other mammals. Thus, a series of normal frontal or sagittal sections through the human brainstem results in skewed sections through the cochlear nuclei. For this reason, blocks of tissue containing the cochlear nuclei were sectioned along the true axes of the nuclei, either in the normal horizontal plane or in the rotated frontal or Received Apr. 25, '78. Accepted Sept. 15, '78

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JEAN KAVANAGH MOORE AND KIRSTEN KJELSBERG OSEN Abbreviations asc. br., ascending branches of cochlear nerve ac. str., acoustic striae cap, dorsolateral cap area of VCN cent., central region of VCN ch. pl., chorioid plexus coch. n., cochlear nerve d.c.n., dorsal cochlear nucleus desc. br., descending branches of cochlear nerve desc. tr. vest., descending tract of vestibular nerve d.m.p.o., dorsomedial periolivary nucleus ep., ependyma floc., flocculus floc. ped., floccular peduncle glob., globular cell i.c.p., inferior cerebellar peduncle inf. coll., inferior colliculus inf. med. vel., inferior medullary velum inf. olive, inferior olive int. nuc. vest., interstitial nucleus of the vestibular nerve lat. rec., lateral recess I.P.o., lateral preolivary nucleus l.s.o., lateral superior olivary nucleus

m.c.p., middle cerebellar peduncle med. str., medullary striae m.p.o., medial preolivary nucleus m.s.o., medial superior olivary nucleus mult., multipolar cell n. VII, facial nerve nuc. VII, facial nucleus 0.c.b.. olivocochlear bundle oct., octopus cell area of VCN p.b.b., pontobulbar body P.o., periolivary nuclei pons, pontine fibers pont. nuc., pontine nuclei pyr., pyramidal cell s.c.P., superior cerebellar peduncle sph., spherical cell and corresponding area of VCN sp. tr. V, spinal tract of trigeminal nerve subarach. space, subarachnoid space trap. b., trapezoid body v.c.n., ventral cochlear nucleus vest. n., vestibular division of VIII nerve vest. nuc., vestibular nuclei IV vent., IV ventricle

Fig. 1 The human brainstem in caudolateral view, with t h e cerebellum removed to expose the dorsal (dcn) and ventral (vcn) cochlear nuclei in the floor of t h e lateral recess. The entire DCN is visible, but the anterior end of t h e VCN is covered by the middle cerebellar peduncle (mcp). The arrow indicates t h e groove or isthmus which separates t h e DCN from the vestibular nuclei (vest nuc). A portion of the pontobulbar body (pbb) forms a n elongate tubercle caudal to t h e DCN, just in front of the attachment of t h e inferior medullary velum (inf med vel). The statoacoustic nerve courses caudally on the surface of the pons, parallel to t h e facial nerve (n VII), with t h e vestibular division (vest n) closer t o the brainstem than the cochlear division (coch n).

sagittal planes. Consequently, in this study, the and refer to settions cut transverse Or parallel to the long axis of the human cochlear complex, . i.e., at an angle of approximately 30" to the frontal and sagittal ,,lanes of the whole brainstem (see inset diagram, fig. 4B). Eleven of the fourteen blocks were embed-

Fig. 2 Camera lucida drawings of regularly spaced, frontal sections, with A the most rwtral section and F t h e most caudal. Inset shows plane of sectioning. Crossinn arrows indicate t h e following directions: D, dorsal; V, -ventral; cL, caudolateral; r M rostromedial. The scale refers t o t h e size of the fixed tissue. Sections A, C, E, and F correspond to photomicrographs in figures 8-11. Arrowhead in F indicates t h e grwve separating the DCN from t h e vestibular nuclei

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ded in celloidin or paraffin and sectioned a t 15 or 20 pm. Regularly spaced series of sections were stained with cresyl violet or thionin for cells; stained by Weigert's iron hematoxylin for myelinated fibers; impregnated with protargol (Bodian, '37); or stained by combined cell-fiber staining techniques, either cresyl violet-luxol fast blue (Kluver and Barrera, '53) or cresyl violet-iron hematoxylin (Pettersen, personal communication). The schematic drawings in figures 2, 3, and 7 and corresponding photomicrographs (figs. 8-15) in the rotated frontal and sagittal planes were made from series of sections obtained from the brain of a four and one-half-year-oldchild, in which every fifth section was stained by the Pettersen method. The horizontal series of drawings in figure 4 were made from material obtained from the brain of a 40-year-old adult. In the material in this study, a variety of fixation and dehydration procedures have been used. Since the magnification of the photomicrographs was not corrected for shrinkage during tissue processing, sizes are not directly comparable from one set of figures to another. In addition to standard histological techniques for cell and fiber staining, enzymatic histochemistry for acetylcholinesterase (AChE) was utilized. Although, as in the cat, (Osen and Roth, '691, no cell types of the complex show the strong positive reaction for AChE typical of cholinergic neurons, some cell staining occurs following prolonged incubation, allowing subregions of the complex to be distinguished by regional variation in staining intensity of cells and neuropil. For this procedure, the three remaining blocks, taken from two brains, were immersed in 10%formaldehyde in 0.1 N cacodylate buffer, pH 7.4, for 24 hours, placed in the same fixative with the addition of 20% DMSO (dimethyl sulfoxide) for an additional 24 hours, and then stored in 20%DMSO in 0.1 N cacodylate buffer for three to four additional days before sectioning on a freezing microtome a t 20 pm or 40 pm in either the rotated frontal or sagittal plane of the nuclei. From each of these blocks, a series of every fifth section was stained by the Koelle method for acetylcholinesterase, using 0.08 mM isoOMPA (Tetraisopropylpyrophosphoramide) as an inhibitor of the nonspecific esterase (for method, see Osen and Roth, '69). Sections were incubated a t room temperature for times varying from 1 to 48 hours. Incubation for 24 hours proved necessary to provide optimal staining, as seen in structures such as

the facial nucleus and olivocochlear bundle. The observed results were essentailly identical in all sections incubated for 24 hours or longer. In addition to the Koelle series, adjacent series of sections from each block were stained for cells (thionin) and fibers (ammoniacal silver, Nauta, '57). OBSERVATIONS

Gross anatomy The human cochlear complex consists of a compact ventral nucleus (VCN) and a crescent-shaped dorsal nucleus (DCN) situated at the pontomedullary junction, lateral to the point of entry of t h e eighth nerve (fig. 1). The cochlear and vestibular components of the nerve, roughly equal in size, curve medially and caudally on the surface of the pons, with the vestibular component of the nerve closest to the brainstem. The cochlear nerve enters the VCN on its ventromedial surface, while the vestibular division penetrates the trapezoid body and proceeds dorsally into the brainstem (figs. 2, 9). In Koelle-stained sections both the cochlear and vestibular nerves are completely negative for AChE (fig. 331, with the exception of the intensely staining fascicles of the olivocochlear bundle (OCB) running in the vestibular nerve (fig. 32). No branches from the OCB to the cochlear nuclei were observed a t any rostrocaudal level. In the undissected human brain, the cochlear nuclei are completely covered by the cerebellum. After removal of the cerebellar hemisphere, including the flocculus, the DCN and posterior VCN are visible in the floor of the lateral recess of the IV ventricle, curving around the lateral surface of the inferior cerebellar peduncle (ICP) (figs. 1, 10).The DCN is separated dorsally from the vestibular area by a shallow notch or isthmus, often marked by the presence of a relatively large vessel (arrowheads, figs. 1, 11).A variable amount of the VCN lies free in the floor of the lateral recess in different specimens. In some cases, the greater part of the nucleus is buried in the fibers of the middle cerebellar peduncle (MCP), while in others only the rostral tip of the nucleus lies deep to these fibers (figs. 1,4). Even the left and right sides of the same individual may differ in this respect. The rostral tip of the VCN in man ends bluntly (fig. 41, in contrast to the tapered rostral tip in lower mammals. Though the posterior part of the cochlear

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Fig. 4 Camera lucida drawings of regularly spaced horizontal sections, with A the most dorsal section and F the most ventral. Inset shows orientation of these horizontal sections and the rotated frontal and sagittal sections presented in figures 2 and 3. Crossing arrows indicate the following directions: R, rostral; C, caudal; M, medial; L, lateral. In D and E, cochlear branches are seen to curve from the nerve root before turning rostral or caudal. Figures C and D illustrate the blunt rostral end of the VCN and the emergence of the trapezoid body from the rostral end of the nucleus.

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complex appears to be completely superficial in man, the nuclei are completely separated from the ependymal surface by a flattened sheet of finely myelinated fibers containing scattered islands of neurons, the pontobulbar body (PBB) (figs. 2-6, 8-15). The PBB is continuous rostrally with the lateral pontine area. Its component cells are similar to those of the pontine nuclei in Nissl-stained material, but show a less positive reaction to AChE staining (fig. 34). After coursing back along the ventral surface of the eighth nerve and

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rostral VCN, the PBB spreads over the lateral surface of both cochlear nuclei. It then continues caudally for a considerable distance on the surface of the ICP, forming a crescentshaped tubercle caudal to the DCN, immediately in front of the point of attachment of the inferior medullary velum (fig. 1). One group of pontobulbar fibers coalesces on the dorsal surface of the DCN t o form a compact band of fibers running subependymally toward the midline on the floor of the IV ventricle as part of the medullary striae (figs. 2-4, 12-15).

Fig. 5 Photomicrograph of the DCN. Sagittal section, Pettersen stain, X 36. The descending cochlear branches (desc br) join the DCN along its ventral and rostral margins, and subsequently take a dorsoventral course parallel to the long axis of the nucleus. Cells are irregularly dispersed within the nucleus, with no preferential orientation. The entire nuclear surface is covered by the pontobulbar body (pbb), including the aggregation of its fibers to form the medullary stria (med s t r ) on the dorsal surface of the nucleus. Fig. 6 Photomicrograph of the DCN. Frontal section, Woelcke stain, X 36. A narrow zone of the surface of the DCN, just beneath the PBB, appears poor in myelinated fibers. On the deep surface of the nucleus a band of heavily myelinated fibers, the acoustic striae, separates the DCN from the underlying ICP.

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Myeloarchitecture

Afferent fibers Within the VCN the cochlear nerve forms a typical wedge-shaped nerve root tapering dorsomedially (figs. 3, 4, 13). Unlike the situation in lower mammals, the rostral and caudal portions of the ventral nucleus are broadly confluent lateral to the nerve root (figs. 2C, 15). Thus a division between an anteroventral (AVCN) and posteroventral (PVCN) nucleus can only arbitrarily be made in man. In myelin-stained saggital sections, the cochlear nerve fibers appear to bifurcate in equal-sized ascending and descending branches, as occurs in other mammals (Cajal, '09; Lorente de NO, '33; Feldman and Harrison, '69; Brawer and Morest, '751, but the initial course of the branches is not entirely directly anterior or posterior. Instead, the branches radiate from the nerve root in a spiral or cartwheel fashion, before curving to run as discrete fascicles to the rostral and caudal poles of the nucleus (fig. 4). After this initial deviation, the ascending branches run to the rostral tip of the VCN, while the descending branches course through the central and posterior VCN to reach the DCN. In protargol-stained sections, some end bulbs of Held were observed in the rostral pole of the VCN. A few similar endings were, however, also found scattered caudal to the nerve root. Though the greater part of the VCN consists of cells lying within the field of the ascending and descending cochlear branches, there is a relatively large marginal zone, or cap area, which lies outside the field of the primary fibers. This cap area covers the lateral surface of the VCN proper, and rises high above it dorsally (cap: figs. 2,3,15). It contains thinly myelinated fibers running predominantly dorsoventrally. Some fibers appear to pass between the cap area and the adjacent VCN, while others can be traced to the top of the ICP (fig. 15). In either case, it was not possible to determine in the material used in this study whether these fibers are entering or leaving the cap area. The descending cochlear branches which continue past the posterior pole of the VCN enter the DCN along its anterior and ventral borders. In contrast to the typical mammalian pattern, the branches do not twist on entering the DCN. Instead, the dark fascicles of cochlear branches fan out across the width of

the DCN and run as individual slightly myelinated, or perhaps unmyelinated, fibers along the dorsoventral axis of the nucleus (figs. 5,6). Although the DCN is generally lightly stained in myelin sections, only the most peripheral rim of the nucleus, immediately beneath the PBB, appears to be nearly free of myelinated fibers (fig. 6). Efferent fibers The ascending pathways from the human cochlear nuclei appear to be directly comparable to those of other mammals in their general organization. On the medial side of the VCN, axons converge to form a relatively large trapezoid body which leaves the dorsomedial aspect of the VCN (figs. 2, 4, 8).The trapezoid body courses medially and rostrally across the medulla to reach the superior olivary complex on both sides of the brainstem. The posterior tip of the VCN does not border on the trapezoid body. Instead a thin layer of thick, beaded, myelinated fibers forms on its medial side and continues dorsally between the DCN and the peduncle as the intermediate acoustic stria (fig. 10). Somewhat thinner myelinated fibers, probably originating in the DCN, converge and run in a dorsomedial direction to form the dorsal acoustic stria, which merges with the intermediate stria adjacent to the ICP. From this site, a clear distinction between the two striae was not possible in our material. The combined band of fibers arches over the top of the ICP and descending vestibular root (figs. 2-4, ll, 12). In the vestibular area, the bundle fans out into separate fascicles, some of which run toward the ipsilateral superior olive, while others run more diagonally toward the midline. It is not possible to distinguish any fibers taking the classical route of the intermediate stria in the human brain, while the fibers coursing toward the midline in the dorsal part of the medulla probably belong to the dorsal stria. In any case, the acoustic striae as a whole appear relatively smaller in man than in other mammals. Cytoarchitecture

The subsequent observations in this study describe the cytoarchitecture of identifiable subregions of the complex. The possible homologies of the various cell classes are considered in the Discussion. Although the question of postmortem changes must always be con-

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sidered in the use of human material, the appearance of neurons in various regions of the cochlear complex was quite consistent from specimen to specimen. In the human, however, the topographical separation of the various cell types seems less complete than in other mammals. The precise extent of each cell area is, therefore, difficult to define, and the borders drawn in illustrations in this study are based on the predominant cell type present, without accounting for overlapping border zones. This is particularly true for the subdivisions of the VCN. The rostral pole of the ventral nucleus (sph: figs. 2-4, 8, 15) is dominated in man by round to oval neurons, which form a fairly homogeneous population and are more regularly and densely packed than any other neurons of the complex. The nuclei of these cells are centrally located, and the Nissl substance tends to form a ring of granules adjacent to the cell membrane (fig. 22). In thionin-stained sections, few, if any, cell processes are visible. Most of the cells of this region fall into the size range of 18-25 pm, with a slight increase in average size from dorsal to ventral. These cells are situated in the rostral portion of the VCN, in the field of the ascending cochlear branches. Scattered cells of this type may be located as far caudally as the cochlear nerve root, but the majority occupy a rather well circumscribed area close to the rostral border of t h e complex. In Koelle-stained sections, these round cells are very faintly stained, showing only a few crystals after prolonged incubation (fig. 30). In addition, the background neuropil of the rostral tip of the nucleus is AChE-negative. Scattered among the rounded cells are polygonal neurons which stain more deeply (sph., fig. 32). These latter cells, which apparently belong to t h e multipolar cell group described below, gradually become more numerous toward the central region of the VCN, in which they are the predominant cell type. The central region of the ventral nucleus (cent: figs. 2-4, 9, 14) stretches from the rostral area of rounded cells almost to the caudal border of the nucleus. It showed no marked variation in its cytoarchitecture which could form t h e basis for division into subregions. Furthermore, the radial path of the cochlear branches as they leave the nerve root made it difficult to say whether a given region in the vicinity of the nerve root is supplied by

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ascending or descending branches, or both. Thus, the usual dichotomy of the ventral nucleus into AVCN and PVCN was not adopted in this study. As in the central region of the VCN in the cat (Osen, '691, this region in man differs from the more rostral and caudal portions of the VCN by the heterogeneity of its cell population. In Nissl-stained material most neurons of the central VCN appear multipolar, with two or more visible dendritic roots (fig. 20a-d). The amount and distribution of Nissl material varies, with some cells containing coarse granules and others exhibiting very fine granular Nissl substance. Both varieties include smaller and larger cells, although the majority of the neurons fall into the same size range as the rounded cells of the rostral tip. In Koelle-stained material, the multipolar cells vary in staining intensity, but the majority are relatively darkly stained (figs. 27, 28, 33). As previously mentioned, scattered cells of this type are also present in the rostral pole of the VCN. One group of neurons in this region can be singled out by their characteristic cellular morphology. These are large, plump oval cells with pale, finely granular cytoplasm, eccentric nuclei, and a fuzzy outline in Nissl sections (fig. 19). In Koelle-stained sections, they appear completely negative, usually even lacking the crystals seen on the rounded cells of the rostral tip (glob: figs. 27, 28b). Such cells are most numerous close to the nerve root, especially lateral to it, and are occasionally observed lying within it, though in contrast to the cat, the cochlear nerve root in man contains only a few neurons. Small neurons were seen only occasionally within the central VCN, but are common along its medial margin, especially within the initial portion of the trapezoid body. The caudal pole of the ventral nucleus (oct: figs. 2-4,10,14) can be seen especially in sagittal section to constitute a cellular area bridging the VCN and DCN. In myelin-stained material, the area is demarcated laterally and ventrally by a capsule of descending cochlear branches. It also contains fascicles of these fibers. In Nissl-stained sections, the neurons of this area are rather similar to the multipolar cells of the central VCN, although more homogeneous in size and staining quality. They are distinguished, as a class, mainly by their large-caliber primary dendrites, which

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give these cells a more notably angular appearance than the multipolar cells (fig. 23). In Koelle staining, these cells are uniformly more faintly positive than the multipolar cells (fig. 31). The fine precipitate on the cell somas and dendrites allows visualization of the long, thick, relatively unbranched dendrites throughout this region. These cells are clustered ventrally, while more dorsally only scattered cells of this type occur among the fascicles of descending cochlear branches (fig. 14). Rostrally this cell area continues gradually into the central VCN, but caudally there is a sharp boundary between it and the adjacent DCN. The cap area of the ventral nucleus (cap: figs. 2-4,9, 15) lies as a flattened sheet of cells over the lateral side of the VCN. It contains a population of uniformly small, spindle-shaped cells oriented for the most part dorsoventrally (fig. 21). In Koelle-stained sections, a layer of precipitate outlines the cell somas and their long, straight dendrites (fig. 29). In addition, there is a light precipitate in the background neuropil which demarcates the cap area from the lightly stained VCN, DCN, and PBB adjacent to i t (figs. 33, 35). This AChE activity of the neuropil could result from staining either of dendrites or axon terminals. In our material, however, no distinctly AChE-positive afferent fibers to this area were identifiable. On the surface of the cap area there was no trace of a layer or clusters of granule cells, nor was there any sign of a plexus of AChE-positive fibers and terminals similar to t h a t which innervates the peripheral granule cell lamina in other mammals. The dorsal nucleus (d.c.n.: figs. 2-4, 11, 1215) is characterized by a greater range in cell size than any other region of the cochlear complex or any adjacent structure. In Nisslstained sections, the majority of the neurons appear fusiform or bipolar, ranging in size from small to medium. The small cells, which are generally similar to cells in the cap area, are elongate and lightly stained. The medium sized neurons are slender, fusiform or triangular cells, with two or three polar dendrites and a relatively dark cytoplasm (fig. 16). Both types of cells are distributed irregularly throughout the DCN without any preferential orientation (figs. 5, 36). Cells are absent only in the outermost rim of the DCN, i.e., in the thin layer deep to the PBB, which is also poor in myelinated fibers. Two other types of cells were seen which

have a more restricted distribution within the nucleus. The dorsal corner of the DCN contains a limited number of minute neurons, each consisting of a small rounded nucleus surrounded by a n almost invisible rim of cytoplasm (arrows, figs. 18, 26). The nuclei are rounder and distinctly larger than the astrocytic nuclei and contain a small, but distinct, nucleolus. The DCN also contains a small number of very large cells with coarse, granular Nissl bodies and prominent nuclei and nucleoli (fig. 17). These cells are situated in the deeper region of the DCN, close to the acoustic striae. In Koelle-stained sections, the DCN is completely negative, except for the large cells of the deeper region, whose positively stained dendrites form a widespread network spanning the entire width and a large part of the length of the nucleus (fig. 25). The medium sized fusiform cells, in contrast, never acquired any precipitate (fig. 24: arrows). The small neurons and the background neuropil were also completely unstained (figs. 26, 34). Even after 48 hours' incubation, the only positively stained structures in the entire DCN were the cell processes, either dendrites or axons, of the large cells of the deeper region. As in the VCN, there was no sign of the peripheral layer of AChE-positive fibers and terminals which is such a prominent feature of the dorsal nucleus in other mammals. DISCUSSION

Gross anatomy The topographic relations of the human cochlear complex are the same as those seen in other mammals, with the exception of the changes caused by the marked increase in size of t h e human cerebellum and related structures. The relative increase in size of the inferior cerebellar peduncle causes the human cochlear nuclei to lie so far laterally on the brainstem as to generally be removed with the cerebellum in routine pathological examination. The enlargement of the middle peduncle, or pons, causes the outward rotation of the rostral end of the complex referred to in the preparation of the material and illustrations in this study. Though, a t first glance, the overall shape of the human cochlear complex appears to differ from t h a t in mammals such as the cat, in having a greater relative height, the human complex if very comparable in shape to a cat cochlear complex cut parallel to the cochleotopic axis of the nuclei (Arnesen and

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Osen, '78; Arnesen et al., '78). .Evidently the apparent increase in height of the human cochlear nuclei is caused by an upward tilting of the complex, that is, a more upright orientation than in other mammals. A small pontobulbar nucleus is located near the pontine nuclei in a t least some mammalian species. This nucleus has been determined to be a precerebellar relay nucleus, receiving input from spinal cord, red nucleus, and face area of sensory-motor cortex, and projecting to the cerebellar cortex (Martin and Walker, '77). Among mammals, only in cetaceans does the pontobulbar body attain dimensions comparable to that seen in man. In the porpoise, the topographical relationship of the PBB to the cochlear nuclei, which it encircles, is similar in every respect to the relationship of the two structures in man (Osen and Jansen, '65). The increase in man and cetaceans in size of the PBB is in accord with the general increase in size of all cerebellar-related structures in these two groups. Although the overall plan of structure of the human cochlear complex is much the same as in other mammals, and the total number of neurons in the complexes of the cat and man are very similar (cat, 100,000; man, 96,000, Hall, '651, differences appear to exist in t h e relative size of the two subnuclei. In terms of relative volume of the dorsal and ventral nuclei, the volume of the DCN in the cat is about one-fourth that of the VCN (Kiang et al., '75). In man, the DCN accounts for a relatively larger part of the complex, with an estimated volume varying between a half and a third that of the VCN (DCN/VCN ratio, 112.3 in subjects from 1to 10 years of age, 1 / 2 3 in subjects over 10 years old, Hall, '65). Differential cell counts of the two nuclei in man (VCN 70,000, DCN 26,000, Hall '65) support this proportionality. Myeloarchitectute Primary and secondary cochlear fibers in man do not stain for AChE and most probably are non-cholinergic, as in the case in other mammals (Godfrey et al., '77). Only in the cap area is the staining of the neuropil suggestive of a small number of AChE-positive terminals, but no positively stained fiber tracts can be distinguished. The initially curved course of the primary cochlear fibers in man probably reflects the spiraling of the intranuclear nerve root postulated by Sando ('65) to reflect t h e spiraling of

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the cochlear nerve as a whole (Arnesen and Osen, '78). Subsequent to this deviation, the organization of the ascending and descending cochlear branches into fascicles running along the rostrocaudal axis of the VCN is so similar to that in other mammals that there is probably no deviation from the dorsal to ventral cochleaotopic pattern found in nonprimates (Rose et al., '59; Sando, '65; Noda and Pirsig, '74; Bourk, '76) and lower primates (Moskowitz and Liu, '72). Interestingly, remarkably high best frequencies have regularly been recorded from the cap area in the cat (Rose et al., '59; Bourk, '76). This would be consistent with the large size of the cap area in the porpoise, which is specialized for reception of ult r a high tonal frequencies, but does not explain the increase in size of the cap area in man. In carnivores and rodents, the twisting of the descending cochlear branches as they enter the DCN results in bands of fibers directed predominantly from caudal to rostra1 in the nucleus (Noort, '69; Osen, '70; Noda and Pirsig, '74), with the most dorsal bands representing the basal portion of the cochlea and the most ventral bands the apical portion. Thus, in these species the cochleotopic axis of the DCN is oriented parallel to t h a t of the VCN, with the highest frequencies located dorsally and the lowest frequencies ventrally (Rose et al., '59). In the monkey DCN, the cochleotopic pattern appears to be similar to that in nonprimates (Moskowitz and Liu, '72). In man, however, the descending branches do not twist, and in contrast to other species, the fibers run from ventral to dorsal, parallel to the long axis of the nucleus (fig. 7). If the preterminal unmyelinated portions of these fibers do not deviate from the course of the main axons, then the cochleotopic axis of the human DCN would be expected to be aligned across the long axis of the nucleus, with the highest frequencies rostrally and the lowest frequencies caudally. The small size of t h e acoustic striae in man is not a good fit with the relatively large size of the DCN. In the porpoise, the discrepancy is reversed, with a very large dorsal stria and a small DCN. The acoustic striae, however, do not contain only ascending fibers (Adams and Warr, '76). In fact, in the cat as many as 50% of the stria1 fibers may be descending to the cochlear nuclei from higher centers (Adams, '76b). The small size of the acoustic striae in man could, therefore, be accounted for by a de-

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Fig. 7 Diagram of t h e human cochlear nuclei in rotated sagittal section, parallel to the true rostrocaudal axis of the nuclear complex. The diagram is a composite drawing based on sagittal sections seen in figures 3 and 12-15. This diagram accurately represents the relative size of the various subregions of the complex, but absolute size, as indicated by the scale. is not corrected for shrinkage during tissue preparation. Crossing arrows indicate the following directions: D, dorsal; lR, laterorostral. The VCN consists of four subregions: a rostra1 area of spherical cells (sph), a caudal area of octopus cells (oct), an intervening central region (cent) containing globular and multipolar cells, and a donolateral cap of small cells (cap). The DCN is not subdivided into layers or repions. Fibers of the cochlear nerve bifurcate within t h e nerve root to form ascending and descending branches, which penetrate all parts of the complex with the exception of the cap area. Fiber direction is predominantly rostrocaudal in the VCN and ventrcdorsal in t h e DCN.

crease in the number of descending fibers, rather than of ascending ones. In the porpoise, on the other hand, the number of descending fibers may be increased. A trend toward less descending influence on the cochlear nuclei in man may also be indicated by the absence of the olivocochlear branches and their target granule cells within the complex. Furthermore, in the human brain, we have not been able to identify the centrifugal fiber bundle of Lorente de NO ('33) so prominent in the cat and rat, or the system of association fibers

usually interconnecting the DCN and VCN. The only sizeable group of possibly efferent fibers are the axons reaching the cap area over the ICP. These negative findings in regard to efferent pathways from the brainstem to the cochlear complex in man imply a reduction in the amount of processing of sensory information done a t this level of the auditory pathway. Cytoarchitecture The various cell classes of the human cochlear nuclei are, with slight modifications, clearly homologous to the cell types previously defined in other mammals. In the following discussion of these homologies we have adopted the terminology used by Osen ('69) in a similar Nissl and myelin study on the cat cochlear nuclei. The cell classifications of Harrison and Warr ('62) and Harrison and Irving ('65, '66a,b), based on protargol-impregnated rat material, and of Brawer et al. ('741, based on Golgi preparations of cat cochlear nuclei, are also used. The cytoarchitectural pattern of the human cochlear nuclei, as defined here and summarized in figure 7, is strikingly similar to t h a t presented by Konigsmark ('73a,b) in his Nissl, silver, myelin and Golgi study on the human cochlear nuclei. Spherical cell area (sph.: fig. 7) The location of the round neurons in the rostral end of the VCN, their characteristic size, shape, and packing density and, most notably, the general homogeneity of the population, support the homology of these cells with the spherical cells described in other mammals (Harrison and Irving, '65, '66a; Webster et al., '68; Osen, '69; Lorente de NO, '76). In the human brain, Dublin ('74, '76) has described a group of "spheroid" neurons in the anterior VCN, which in his Bodian preparations receive large end bulbs of the type typically observed on mammalian spherical cells (Ramon y Cajal, '09; Lorente de NO, '33, '76; Lenn and Reese, '66; Feldman and Harrison, '69; Osen, '70; Brawer and Morest, '75). Such end bulbs may not be entirely restricted to spherical cells, since in this study, as in the r a t (Feldman and Harrison, '691, a few similar endings were observed caudal to the nerve root as well. In carnivores and rodents, the spherical cells have been divided on the basis of size into two classes, the large and small spherical cells of Osen ('691, or c- and i-cells of Harrison and

COCHLEAR NUCLEI IN MAN

Irving ('65, '66a). In these nonprimate mammals, the two cell groups form clearly separate areas, with larger cells situated ventrally and smaller cells dorsally. A segregation of spherical neurons into two types is not apparent in man, so that although a slight gradient to larger cells ventrally may exist, we regard the spherical cell area in the human VCN as unitary, as does Konigsmark ('73b). Central area of VCN (cent., fig. 7) In the cat, the central region of the VCN consists of overlapping areas of multipolar and globular cells (Osen, '69). Globular cells, first described by Harrison and Warr ('621, have consistently been noted as a distinct and homogeneous cell type in lower mammals (Harrison and Irving, '65, '66a; Webster et al., '68; Pirsig, '68). These globular cells probably represent a subgroup of the bushy cells defined by Brawer et al. ('74). The multipolar cells, on the other hand, are normally a heterogeneous class of neurons, including the d, e, f, and possibly other cell types in the Harrison and Irving classification. They are probably a part of the stellate cell group of Brawer et al. ('74). In man, the heterogeneous assembly of multipolar cells and the relatively uniform group of oval or globular cells in the central VCN seem to correspond very closely to their counterparts in other mammals. In the human brain, both Dublin ('74, '76) and Konigsmark ('73b) describe cells with an oval or tear-drop shape which are most numerous in the nerve root region of the VCN. The human appears to differ from the cat in that these cells are relatively less numerous, with few such cells found within the cochlear nerve root in man. The multipolar cells in man are very numerous, filling the central region of the VCN and being found scattered all the way to the rostral pole of the nucleus. Similar observations on the distribution of stellate cells were made by Brawer et al. ('74) in the cat. A point of difference between the central VCN in man and other mammals is that most of the small neurons of the human VCN are confined to the border zones of the nucleus, with relatively few small cells intermingled with the larger multipolar and globular cells, as is the case in the cat and rat. Octopus cell area (oct.: fig. 7) A consistent feature of the mammalian VCN is a sharply defined region in the caudal

405

VCN containing only one cell type, the octopus cells (Harrison and Irving, '66b; Webster et al., '68; Pirsig, '68; Osen, '69; Kane, '73; Brawer, '74; Godfrey et al., '75). The term octopus cells was coined because of the long, stout primary dendrites which tend to arise from one side of the cell body and run a t right angles to the direction of the descending cochlear branches. In man, the cytology of the caudal pole of the VCN is not so strikingly different from t h a t of the central VCN as in lower mammals, and a distinct border between central and posterior VCN is difficult to define. Nonetheless, the large primary dendrites of the neurons a t the caudal pole of the VCN, the relative homogeneity of the population, including their consistently negative reaction in AChE staining, and the relationship of these cells to the intermediate acoustic stria, justify a homology of these neurons with the octopus cells of other mammals. In the human cochlear complex, the octopus cell area appears small (Konigsmark, '73b1, which is consistent with the small size of the intermediate stria, but the difficulty in defining the absolute rostra1 limit of the octopus cell area must be kept in mind in estimating the size of this area in man. Cap area (cap: fig. 7) A laterodorsal cap area is not generally mentioned in descriptions of the cochlear nuclei in rodents, but such an area is a definite feature of t h e nuclear complex in the cat (Lorente de NO, '33; osen, '69; Bourk, '76; Adams, '77; Cant and Morest, '77) and in the porpoise (Osen and Jansen, '65). The prominent cap area defined in this study appears to correspond to the peripheral polymorphous cell area outlined by Konigsmark ('73b1, with the exception that his area includes the overlying pontobulbar body. In man, as in the cat (Osen and Roth, '691, the neuropil surrounding the small cells in the cap area stands in contrast to the adjacent VCN by virtue of its relatively strong AChE staining, but the significance of this positive staining is not known. In the cat, cap cells probably project centrally along the trapezoid body (Osen, '72; Adams and Warr, '761, with the inferior colliculus as their most distant area of termination (Adams, '77). If the axons of the cap cells do indeed leave the complex by way of the trapezoid body, then the possibility must be considered that the relatively large

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number of fibers passing between the cap area and the dorsal route over the ICP are efferent or descending fibers from the brainstem to the cochlear complex. Both the human and cetacean cochlear complexes lack the granule cell layer which normally bounds the, cap area laterally. In man, this absence of the granular layer is known to be the end result of a phylogenetic trend in primates toward regression of the granule cell system in the entire cochlear complex (Moore, '78). In addition, the human cochlear complex lacks the dense plexus of AChE-positive fibers and terminals which innervates the granule cell lamina in other mammals (Rasmussen, '60, '67; Osen and Roth, '69; McDonald and Rasmussen, '71). Dorsal cochlear nucleus (d.c.n.: fig. 7) Difficulties in establishing the extent of the DCN in man have resulted in a variety of interpretations of its size. At its medial border towards the vestibular nuclei, there is no striking cytological boundary. At this point, the chief difference between the cochlear and vestibular areas is the greater range of cell size in the DCN. The border defined between the cochlear and vestibular areas in this study appears more lateral than the one presented in Sadjadpour and Brodal's ('67) study of the human vestibular nuclei, and it is possible that the y-group of the vestibular complex, which they could not identify, was included by those authors as part of the DCN. The other usual variation is the inclusion in most illustrations and atlases of the pontobulbar body as the most superficial layer of the DCN (e.g., Konigsmark, '73b). A number of descriptions (e.g., Stotler, '57; Dublin, '74) refer to the human DCN as vestigial. The difficulties in definition of the human DCN are obviously related to the difference in its cytoarchitecture from that seen in nonprimate species, particularly in the absence of a sharp cell and fiber lamination of the nucleus. This difference in structure appears to result largely from the absence in the human cochlear complex of a functional granule cell system. In contrast to the usual mammalian pattern, the human cochlear complex contains only a vestige of a granule cell layer, represented by the collection of minute neurons in the dorsalmost corner of the DCN. The thin myelin-poor rim of the DCN beneath the PBB may represent a remnant of the molecular

layer. In nonprimate cochlear nuclei, all granule cells of the DCN and VCN send their axons into the molecular layer of the DCN to converge on pyramidal cell apical dendrites (Mugnaini et al., '78). Thus, with the virtually total loss of cochlear granule cells in higher primates, the molecular layer, normally composed of their axons, must be correspondingly reduced. Since granule cells apparently represent the main target of the AChE-positive branches of the olivocochlear bundle (Rasmussen, '60, '67; Osen and Roth, '69; McDonald and Rasmussen, '71), it is not surprising that this plexus is not observed in the human DCN. The remaining cell types, nonetheless, appear homologous to those of other mammals. The medium sized fusiform cells in the human DCN probably correspond to the more rigidly geometric pyramidal cells in the cat. The chief basis for this homology are the comparative anatomical observations in a series of primates, in which the pyramidal cells, originally peripheral in prosimians, are seen to become progressively incorporated into the deeper DCN in monkeys and apes (Moskowitz, '69; Moore, '78). The smaller spindle-shaped or fusiform cells in man probably correspond to the small neurons (Osen, '69) which are encountered in all layers of the mammalian DCN. The very large cells, with extensive dendritic arborizations, are clearly similar in their morphology and location to the mammalian giant cells, though they are decidedly rarer in man than in the cat. These cell homologies are strongly supported by the Koelle staining. In man, as in the cat (Osen and Roth, '691, the pyramidal cells are definitely AChEnegative, while the giant cells and their dendrites are moderately stained for AChE. In conclusion, all classes of neurons previously identified in the cochlear nuclei of other mammals can be defined in the human cochlear nuclei, though two cell types, granule cells and giant cells, are extremely rare. A true quantitative determination of the size of the various cell areas in man is not warranted by this study, in view of the range of differences in subjects' age, postmortem changes, and fixation procedures. By rough estimate, however, i t seems that the multipolar cells, cap cells, and pyramidal cells, all of which project to the inferior colliculus (Osen, '72; Adams, '76a, '771, have increased their relative share in the complex. In contrast, the spherical cells, globular cells, and octopus

COCHLEAR NUCLEI IN MAN

cells, which have the superior olive as their main target (Harrison and Irving, '66a, Fernandez and Karapas, '67; Warr, '66, '69, '72; Strominger and Strominger, '71; Strominger, '73), seem less numerous in man than in other mammals. This would be consistant with the overall trend toward increased projection to mid- and forebrain levels in sensory systems of the human brain. ACKNOWLEDGMENTS

Sincere thanks are due t o Mrs. Nanti StangLund for her skilled assistance in the preparation of the drawings, and to Mr. E. Risnes for valuable help in the photographic work. This research was supported by USPHS Grants NS-12267 and HD-04583 and 2G-94 from the National Institutes of Health, and by the Norwegian Research Council and the Norwegian Academy of Science and Letters. LITERATURE CITED Adams, J. C. 1976a Types of cells in the cochlear nuclei t h a t project to the interior colliculus in the cat. Anat. Rec., 184: 340. 1976b Single unit studies on the dorsal and intermediate acoustic striae. J. Comp. Neur., 170: 97-106. 1977 Organization of the margins of t h e anteroventral cochlear nucleus. Anat. Rec., 187: 520. Adams, J. C., and W. B. Warr 1976 Origins of axons in the cat's acoustic striae determined by injection of horseradish peroxidase into severed tracts. J. Comp. Neur., 170: 107-122. Arnesen, A. R., and K. K. Osen 1978 The cochlear nerve in t h e cat: topography, tonotopy and fiber spectrum. J. Comp. Neur., 178: 661-678. Arnesen, A. R., K. K. Osen and E. Mugnaini 1978 Temporal and spatial sequence of anterograde degeneration in the cochlear nerve fibers of the cat. A light microscopic study. J. Comp. Neur., 178: 679-696. Bacsik, R. D., and N. L. Strominger 1973 The cytoarchitecture of the human anteroventral cochlear nucleus. J. Comp. Neur., 147: 281-290. Bodian, D. 1937 The staining of paraffin section of nervous tissue with activated protargol. The role of fixatives. Anat. Rec., 69: 153-162. Bourk, T. R. 1976 Electrical Responses of Neural Units in t h e Anteroventral Cochlear Nucleus of the Cat. Thesis, Massachusetts Institute of Technology, Boston, 385 pp. Brawer, J. R., and K. K. Morest 1975 Relations between auditory nerve endings and cell types in the cats anteroventral cochlear nucleus seen with the Golgi method and Nomarski optics. J. Comp. Neur., 169: 491-506. Brawer, J. R., D. K. Morest and E. C. Kane 1974 The neuronal architecture of the cochlear nucleus of t h e cat. J. Comp. Neur., 155: 251-300. Cajal, S. R. y 1909 Histologie du Systeme Nerveux de I'Homme e t des Vertebrb. A. Moloine, Paris. Chap., 28; 774-838. Cant, N. B., and K. K. Morest 1977 Small cells of the anterior subdivision of the anteroventral cochlear nucleus (AVCN) of the cat. Anat. Rec., 287: 544. Dublin, W. B. 1974 Cytoarchitecture of the cochlear nuclei. Report of a n illustrative case of erythroblastosis. Arch. Otolaryngol., 200: 355-359.

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1976 Fundamentals of Sensorineural Auditory Pathology. Charles C Thomas, Springfield, Illinois, 229 pp. Feldman, M., and J. M. Harrison 1969 The acoustic nerve projection to t h e ventral cochlear nucleus in t h e rat. A Golgi study. J. Comp. Neur., 137: 267-292. Fernandez, C., and F. Karapas 1967 The course and termination of the striae of Monakow and Held in t h e cat. J. Comp. Neur., 137: 267-292. Fuse, G. 1913 Das Ganglion ventrale und das Tuberculum acusticum bei einigen Saugern und beim Menschen. Arb. Hirnanat. Inst. Zurich, 7: 1-210. Godfrey, D. A., N. Y. S. Kiang and B. E. Norris 1975 Single unit activity in the posteroventral cochlear nucleus of t h e cat. J. Comp. Neur., 162: 247-268. Godfrey, D. A., A. D. Williams and F. M. Matschinsky 1977 Quantitative histochemical mapping of enzymes of t h e cholinergic system in t h e cat cochlear nucleus. J. Histochem. Cytochem., 25: 397-416. Hall, J. G. 1965 The cochlea and the cochlear nuclei in neonatal asphysix. A histological study. Universitetsforlaget, Oslo, 93 pp. Harrison, J. M., and R. Irving 1965 The anterior ventral cochlear nucleus. J. Comp. Neur., 124: 15-24. 1966a Ascending connections of the anterior ventral cochlear nucleus in the rat. J. Comp. Neur., 126: 51-64. 1966b The organization of the posterior ventral cochlear nucleus in the rat. J. Comp. Neur., 126: 391-402. Harrison, J. M., and W. B. Warr 1962 A study of the cochlear nuclei and ascending auditory pathways of the medulla. J. Comp. Neur., 119: 341-379. Kane, E. C. 1973 Octopus cells in the cochlear nucleus of the cat: heterotypic synapses upon homeotypic neurons. Intern. J. Neurosci., 5: 251-279. Kiang, N. Y. S., D. A. Godfrey, B. E. Norris and S. E. Moxon 1975 A block model of the cat cochlear nucleus. J. Comp. Neur., 162: 221-246. Konigsmark, B. W. 1969 Neuronal population of the ventral cochlear nucleus in man. Anat. Rec., 163: 213. 1973a Cellular organization of t h e cochlear nuclei in man. J. Neuropath. exp. Neurol., 32: 153-154. 197313 Neuroanatomy of t h e auditory system. Arch. Otolaryngol., 98: 397-413. Konigsmark, B. W., and E. A. Murphy 1972 Volume of the ventral cochlear nucleus in man: its relationship to neuronal population and age. J. Neuropath. exp. Neurol., 32: 304-316. Kluver, H., and E. Barrera 1953 A method for combined staining of cells and fibers in the nervous system. J. Neuropath. exp. Neurol., 12: 400-403. Lenn, N. J., and T. S. Reese 1966 The fine structure of nerve endings in the nucleus of t h e trapezoid body and the ventral cochlear nucleus. Am. J. Anat., 118: 375-390. Lorente de NO, R. 1933 Anatomy of the eighth nerve: 111 General plan of structure of the primary cochlear nuclei. Laryngoscope, 43: 327-350. 1976 Some unresolved problems concerning the cochlear nerve. Ann. Otol. Rhinol. Laryngol., 85: 1-28. Martin, G. F., and J. M. Walker 1977 The nucleus of the pontobulbar body. A separate pontocerebellar nucleus? SOC. for Neurosci. Abs., 3: 58. McDonald, D. M., and G. L. Rasmussen 1971 Ultrastructural characteristics of synaptic endings in the cochlear nucleus having acetylcholinesterase activity. Brain Res., 28: 1-18, Moore, J. K (1978, in preparation) The primate cochlear nuclei: Loss of lamination as a phylogenetic process. Moskowitz, N. 1969 Comparative aspects of some fea-

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tures of th e central auditory system of primates. Ann. N. Y. Acad. Sci., 167: 357-369. Moskowitz, N., and J.-C. Liu 1972 Central projections of the spiral ganglion of the squirrel monkey. J. Comp. Neur., 144: 335-344. Mugnaini, E., G. Korte, W. B. Warr and K. K. Osen (1978, in preparation) The granule cell system in the cat cochlear nuclei. Nauta, W. J. H. 1957 Silver impregnation of degeneratir.g axons. In: New Research Techniques of Neuroanatomy, W. F. Windle, ed. Charles C Thomas, Springfield, Illinois, pp. 17-26. Noda, Y., and W. Pirsig 1974 Anatomical projection of the cochlea to the cochlear nuclei of the guinea pig. Arch. Oto-Rhino-Laryng., 208: 107-120. Osen, K. K. 1969 The cytoarchitecture of the cochlear nuclei in the cat. J. Comp. Neur., 136: 453-484. 1970 Course and termination of t he primary afferents in the cochlear nuclei of the cat. An experimental anatomical study. Arch. Ital. Biol., 108: 21-51. 1972 Projections of the cochlear nuclei on the inferior colliculus in the cat. J. Comp. Neur., 144: 355-372. Osen, K. K., and J. Jansen 1965 The cochlear nuclei in the common porpoise, Phocaena Phocaena. J. Comp. Neur., 125: 223-257. Osen, K. K., and K. Roth 1969 Histochemical localization of cholinesterases in the cochlear nuclei of the cat, with notes on the origin of acetycholinesterase-positiveafferents and the superior olive. Brain Res., 16: 165-184. Pettersen, E. Personal communication. Pirsig, W. 1968 Regionen, Zelltypen und Synapsen im ventralen Nucleus cochlearis des Meerschweinchens. Arch. Klin. exp. 0hr.-Nas.- Kehlk. Heilk., 192: 333-350. Rasmussen, G. L. 1946 The olivary peduncle and other fiber projections of the superior olivary complex. J. Comp. Neur., 84: 141-200.

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Efferent fibers of the cochlear nerve and cochlear nucleus. In: Neural Mechanisms of the Auditory and Vestibular Systems. G. L. Rasmussen and W. R. Windle, eds. Charles C Thomas, Springfield, Illinois, pp. 105-115. 1967 Efferent connections of the cochlear nucleus. In: Sensorineural Hearing Processes and Disorders. A. B. Graham, ed. Churchill, London, pp. 61-75. Rose, J. E., R. Galarnbos and J. R. Hughes 1959 Microelectrode studies of the cochlear nuclei of t h e cat. Bull. Johns Hopkins Hosp., 104: 211-251. Sadjadpour, K., and A. Brodal 1967 The vestibular nuclei in man. A morphological study in the light of experimental findings in the cat. J. Hirnforsch., 10: 299-323. Sando, I. 1965 The anatomical relationships of the cochlear nerve fibers. Acta Oto-laryng., 59: 417-436. Stotler, W. A. 1957 A comparison of the cochlear nuclei of t he primate and carnivore brainstem. Anat. Rec., 127: 374. Strominger, N. L. 1973 The origins, course, and distribution of the dorsal and intermediate acoustic striae in the rhesus monkey. J. Comp. Neur., 147: 209-234. Strominger, N. L., and A. Strominger 1971 Ascending brain stem projections of the anteroventral cochlear nucleus of the rhesus monkey. J. a m p . Neur., 143: 217-242. Warr, W. B. 1966 Fiber degeneration following lesions in the anterior neutral nucleus of the cat. Exp. Neurol., 14: 453-474. 1969 Fiber degeneration following lesions in the posteroventral cochlear nucleus of the cat. Exp. Neurol., 23: 140-155. 1972 Fiber degeneration following lesions in the multipolar and globular cell areas in the ventral cochlear nucleus of the cat. Brain Res., 40: 247-270. Webster, D. B., R. F. Ackermann and G. C. Longs 1968 Central auditory system of the kangaroo rat Dipodomys merriami. J. Comp. Neur., 133: 477-494.

PLATE I EXPLANATION OF FIGURES

Figures 8-11 are photomicrographs of 15-pm rotated frontal sections corresponding to sections A, C, E, and F in figure 2, with 8 the most rostra1 section and 11 the most caudal. Subdivisions indicated by dashed lines. Pettersen stain,

X

13.

8 Cochlear (coch n) and vestibular (vest n) components of nerve VIII are easily distinguished on the basis of differential staining. Spherical cell area (sph) is seen a t the level of its greatest extent. The VCN is

separated from the ependymal surface of the lateral recess Oat rec) by a thin layer of pontobulbar fibers (pbb). The large trapezoid body (trap b) leaves the rostrodorsal aspect of the VCN. 9 The cochlear nerve enters t he VCN on its medial aide, and the anterior and posterior portions of the nucleus are confluent lateral to the nerve root. The central region of the VCN (cent) is covered laterally by the cap area (cap), but there is no peripheral granule layer. Fiber bundles of the trapezoid body interdigitate with the vestibular nerve (vest n). The fiber bundle labeled !!was not definitely identified, but may be fibers joining t he inferior cerebellar peduncle (icp). 10 The octopus cell area (oct) at t he posterior tip of the VCN is continuous with the DCN. The DCN, like the VCN, is at all points separated from t he ependymal surface by the pontobulbar body (pbb). The acoustic striae (ac str) are seen as a thin layer of heavily myelinated fibers on the deep surface of the nuclei. 11 The acoustic striae course over the inferior peduncle (icp) and descending tract of the vestibular nerve (desc t r vest), with t he dorsal and intermediate striae not clearly separated. The rectangular area is reproduced a t higher magnification in figure 36. Arrowhead indicates border between DCN and vestibular nuclei (vest nuc).

COCHLEAR NUCLEI IN MAN Jean Kavanagh Moore and Kirsten Kjelsberg Osen

PLATE 1

PLATE 2 EXPLANATION OF FIGURES

Figures 12-15 are photomicrographs of 15-pm rotated sagittal sections corresponding approximately to sections A-D in figure 3, with 12 the most medial section and 15 the most lateral. Dashed lines indicate subdivision of t h e complex. Pettersen stain, X 13. 12 The trapezoid body (trap b) is divided into a rostral and a caudal portion by fascicles of vestibular nerve fibers (vest n). The acoustic striae (ac str) form the deep border of the DCN, while t h e medullary stria (med str) forms within the pontobulbar body (pbb) on the surface of the nucleus. 13 The cochlear nerve gives origin to ascending and descending branches. The trapezoid body (trap b) leaves the rostral VCN, while t h e acoustic striae (ac str) lie on t h e deep surface of t h e DCN. 14 The cap area (cap) lies above t h e area pierced by cochlear fibers. Ascending cochlear branches innervate t h e spherical cell area, while descending branches surround and penetrate t h e octopus cell area (oct).

15 The cap area (cap) is most extensive on t h e lateral side of t h e complex. Descending cochlear branches reach t h e anterior and ventral borders of t h e DCN. The pontobulbar body (pbb) is most extensive on the caudolateral surface of the complex. Its deep border is indicated by a dashed line.

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COCHLEAR NUCLEI IN MAN Jean Kavanagh Moore and Kiraten Kjelsberg Oeen

PLATE

2

PLATE 3 EXPLANATION OF FIGURES

Figures 16-23 are photomicrographs of various cell types of the cochlear nuclei. Cresyl violet stain, X 300. 16 Pyramidal cells.

17 Giant cells 18 Granule cells, marked by arrows.

19 Globular cells.

20 a b c d

Multipolar cells. Fine granular, large. Fine granular, small. Coarse granular, large. Coarse granular, small.

21 Cap cells

22 Spherical cells 23 Octopus cells.

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COCHLEAR NUCLEI IN MAN Jean Kavanagh Moore and Kirsten Kjelsberg Osen

PLATE 3

PLATE 4 EXPLANATION OF FIGURES

Figures 24-31are photomicrographs of various cell types in Koelle stain, 40 hours in. cubation, X 300.

24 Pyramidal cells, unstained, marked by arrows. 25 Giant cell bodies and dendrites, moderately stained. 26 Granule cells, indicated by arrows. Border between pontobulbar body (pbbf and DCN indicated by horizontal line. 27 Globular cells, unstained, encircled. 28 a b c

Multipolar cells of various types. strongly stained. lightly or strongly stained, in contrast to unstained globular cell. strongly stained, in contrast to weakly stained spherical cell.

29 Cap cells and neuropil, moderately stained

30 Spherical cells, weakly stained, encircled.

31 Octopus cells, somas and dendrites lightly stained

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COCHLEAR NUCLEI IN MAN Jean Kavanagh Moore and Kirsten Kjelsberg Osen

PLATE 4

PLATE 5 EXPLANATION OF FIGURES

Figures 32-34 are photomicrographs of rotated frontal sections through t h e cochlear nuclei stained by the Koelle method, 40 hours’ incubation, X 13. Figure 32 is the most rostra1 section and figure 34 t h e most caudal. 32 The vestibular (vest n) nerve is unstained except for t h e AChE-positive olivocochlear bundle (ocb). The sperical cell area (sph) contains many lightly staining neurons, with some scattered darkly stained multipolar cells. Darkly stained cells predominate in the central region (cent). The group of darkly stained neurons lateral to t h e VCN probably belongs to t h e pontine nuclei (pont nuc). The inferior (icp) and middle (mcp) cerebellar peduncles appear negative. 33 The central region of the VCN is covered laterally by t h e cap area (cap), which is reproduced a t higher magnification in figure 35. The cochlear nerve (coch n) is unstained. 34 Neurons in the octopus cell area (oct) appear lightly stained, while the dorsal cochlear nucleus (dcn), acoustic striae (ac str), and pontobulbar body (pbb) are unstained. 35 The rectangular area in B is shown here a t higher magnification, x 130. Both cap cells and neuropil stain moderately for AChE. 36 The rectangular area in figure 11 is shown here a t higher magnification, Pettersen stain, X 86. The DCN is unlaminated and its cells distributed randomly with no preferential orientation. Myelinated axons course dorsomedially to join the acoustic striae (ac str).

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COCHLEAR NUCLEI IN MAN Jean Kavanagh Moore and Kirsten Kjelsherg Osen

PLATE 5