Adv. Oto-Rhino-Laryng., vol. 20, pp. 337-356 (Karger, Basel 1973) Auditory Neurons of the Brain Stem l D. K. MOREST Department of Anatomy, Harvard Medical School and Eaton-Peabody Laboratory of Auditory Physiology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts I. Introduction One difficulty in understanding the role of the central auditory system in hearing disorders is lack of information concerning the processes by which auditory nerve cells in the brain normally represent acoustic information and transform it in the course of the auditory analysis. Electrophysiological observations have shown that auditory neurons respond to specific acoustic stimuli in predictable, even stereotyped patterns [KIANG et at., 1965a, b]. On the basis of this regularity, it would appear that the discharge patterns of the neurons could constitute a kind of auditory code. However, it will not be possible to explain how the auditory neurons are able to encode information in specific electrical patterns until the structural basis for this kind of activity has been clarified. Moreover, the morphological features of nerve cells that are directly related to their analytical capacities must be recognized before a functional neuropathology of the central auditory system can be developed at the cellular level. At the very least, one would like to know what cytological features of nerve cells to study in pathological specimens. Recent investigations delineated some of the morphological characteristics of nerve cells that may relate directly to the central hearing mechanisms [MoREsT, 1964a, b, c, 1965a, b, 1968a, b, 1971]. The results suggest that, if neurons are predictable and typical in their electrical discharge patterns, they are equally regular and stereotyped in many of their morphological attributes. Some of these structural regularities could be related to the functions of the auditory centers. Morphological features of nerve cells that Downloaded by: Université René Descartes Paris 5 126.96.36.199 - 10/26/2017 3:33:57 AM 1 Supported by US Public Health Service grant NS 06115, with the technical aid of Mrs. A. B. GREENE. MOREST 338 define their physiological capacities are the arrangement and geometrical patterns of their processes, their axons and dendrites, and the sequences of synaptic connections established by these processes. Methods The rapid Golgi technique, namely, silver chromate impregnation, is the method par excellence for the microscopic demonstration of neurons and their processes. When this technique is applied after perfusion-fixation of the brain [MOREST and MOREST, 1966], it may be reliably correlated with observations by other methods, including silver degeneration methods [MOREST, 1965b] and electron microscopy [MOREST, 1971]. The relevant anatomical principles can be illustrated by reference to the groups of auditory neurons in the trapezoid body, in particular the superior olive and the medial nucleus of the trapezoid body. These cell groups are related to the ascending and descending auditory pathways (fig. 1). The ascending pathway begins with the secondary auditory neurons of the cochlear nucleus, which receives the synaptic endings of the auditory nerve fibers from the cochlea. The neurons of the cochlear nucleus send axons to the superior olivary complex, including the medial nucleus of the trapezoid body, and to the inferior colliculus. Neurons in the inferior colliculus project to the medial geniculate body, which in turn projects upon the auditory cortex. There are commissures of the cortex and the brain stem which provide for bilateral representations of the cochlea. These are the main pathways of the ascending auditory system. The superior olive and the inferior colliculus are also important centers in the descending auditory system. The inferior colliculus receives corticofugal axons from the auditory cortex and in turn projects to peri-olivary cell groups of the superior olive. These parts of the superior olivary complex give rise to the olivo-cochlear bundle, which ends upon hair cells in the cochlea. All of these pathways are tonotopically organized. First of all, in the cochlear nuclei of the cat the auditory nerve fibers establish a sequential correspondence between points in the cochlea and sectors in the cochlear nucleus (fig. I), such that the basal coil is represented most dorsomedially in each cochlear nucleus and the more apical turns successively more ventrolaterally in the cochlear nuclei [LORENTE DE No, 1933; RASMUSSEN et al., Downloaded by: Université René Descartes Paris 5 188.8.131.52 - 10/26/2017 3:33:57 AM Results Auditory Neurons of the Brain Stem 339 Base Cochlea Nuclei Apex Corp. callosum ~a cortex~ Radiation Thalamus Midbrain Pons Medulla Descending Fig. 1. Top: Scheme of the tonotopic organization of the dorsal and ventral cochlear nuclei as a frequency map of the cochlea. The spatial arrangement of the axonal branches of the auditory nerve in the cochlear nucleus establishes an orderly correspondence of successively more apical regions of the cochlea with progressively more ventrolateral sectors of the cochlear nucleus. Bottom: The principal pathways of the ascending and descending auditory systems. RF = reticular formation; ML = medial lemniscus. Downloaded by: Université René Descartes Paris 5 184.108.40.206 - 10/26/2017 3:33:57 AM Ascending MOREST 340 Fig. 2. Photomicrograph of a rapid Golgi impregnation of the trapezoid body in a transverse section from a I-day-old cat. A = fibers of the trapezoid body; B = medial trapezoid nucleus; C = medial superior olive; D = dorsomedial peri-olivary nucleus; E = ventral trapezoid nucleus; F, G, and K = peri-olivary cell groups; H = lateral superior olive; J = lateral trapezoid nucleus. Thin arrows (left) show the direction of unimpregnated abducens nerve rootlets. Scale = 100 flm. Downloaded by: Université René Descartes Paris 5 220.127.116.11 - 10/26/2017 3:33:57 AM 1960]. This amounts to a frequency map of the cochlea. This tonotopic map is maintained in all subsequent parts of the auditory system [WARR, 1966; MOREST, 1968a; ROSE et al., 1963; MOREST, 1965a; WOOLSEY and WALZL, 1942]. As it will be seen, this circumstance permits us to interpret several prominent features of the auditory neurons. The superior olive in the cat receives bilateral projections ofaxons from the cochlear nuclei (fig. 1). Within the superior olivary complex these afferent 341 axons end in distinct groups of neurons (fig. 2). These may be distinguished by the different patterns in which the afferent axons are arranged. In the medial superior olive the ends of the axons line up along the dorsoventral axis of the nucleus. A linear arrangement of the different axons also occurs in the lateral superior olive, but this nucleus has an S-shaped configuration. Nests of axonal endings from the cochlear nucleus occur in several groups of neurons located on the perimeter of the medial and lateral superior olivary nuclei. These nests define the peri-olivary nuclei, which are thought to give rise to the crossed and uncrossed olivo-cochlear bundles. The dorsomedial peri-olivary nucleus in particular has been indicated by RASMUSSEN  as one source of the crossed olivo-cochlear bundle. Medial to the medial superior olive is the medial trapezoid nucleus, in which many of the axons from the contralateral ventral cochlear nucleus form very large endings, the calyces of Held. The medial superior olive receives projections from both cochlear nuclei. It is one of several places in the brain where acoustic information from both sides of the head can be integrated, and binaural interactions may occur. The afferent axonal endings from the cochlear nuclei line up in an orderly dorsal-to-ventral sequence. This sequence corresponds to the tonotopic organization of the cochlear nucleus and cochlea, such that the more basal segments of the cochlea are represented more ventrally [WARR, 1966]. The axons from the contralateral cochlear nucleus end in the medial half of the nucleus; those from the ipsilateral cochlear nucleus end in the lateral half [STOTLER, 1953]. The end of each axon branches predominantly within a horizontal layer of the nucleus. At the same time the neurons of the medial superior olive have a layered arrangement (fig. 3). The dendrites of these neurons occupy elongated, oval fields, flattened in the horizontal plane. This arrangement of afferent axons and the dendrites would provide the optimum structural basis for preserving the tonotopic map of the cochlear nucleus. The dendritic field of each neuron would intercept a narrow sector of the spectrum of afferent fibers, each of which branches so as to maximize the synaptic contacts within a narrow sector of the nucleus. Since the medial dendrites would receive synaptic endings from the contralateral cochlear nucleus, binaural interactions could occur in the individual auditory neurons. It is not yet certain whether these responses are involved in localizing sounds in space, in the lateralization of acoustic reflexes, or in some other binaural phenomenon. Thus it appears that in the medial superior olive of the cat the geometrical pattern of the axonal endings and of the dendritic processes contacting Downloaded by: Université René Descartes Paris 5 18.104.22.168 - 10/26/2017 3:33:57 AM Auditory Neurons of the Brain Stem Downloaded by: Université René Descartes Paris 5 22.214.171.124 - 10/26/2017 3:33:57 AM Fig. 3. Scheme of the trapezoid body as reconstructed by serial transverse sections from a rapid Golgi impregnation of a 14-day-old cat. A, B, C, and D = axonal calyces, principal neuron, stellate neuron, and elongate neurons, respectively, of the medial trapezoid nucleus; E and F = radiate and elongate neurons, respectively, of the dorsomedial peri-olivary nucleus; G = large neurons of the nucleus pont is centralis caudalis; H = small neuron of the same nucleus: the axon forms collateral branches to the left of the perikaryon; J = neuron in the dorsal peri-olivary group; K = collateral of an axon crossing in the trapezoid body, which ascends in the root of the abducens nerve (6). LSO = medial lobe of the lateral superior olivary nucleus; MSO = medial superior olivary nucleus; TV = ventral trapezoid nucleus; TVM = a medial extension of the preceding, associated with crossing trapezoid fibers. a = Axonal collateral of principal neuron projecting to the dorsomedial peri-olivary nucleus; b = collaterals of calyx fibers projecting to the dorsomedial peri-olivary nucleus; c = ventromedial peri-olivary group. Modified from figure 4 in MOREST [1968a]. ~ ~ I /-/F~~ ~m ~, Fig. 4. Calyces of Held and axonal collaterals in a transverse plane of the medial trapezoid nucleus of a newborn cat. The neurons at the top actually appear in an adjacent section. A = collaterals of the principal neuron that leave the section in a ventrolateral direction; B = collateral of the preceding, arborizing in the dorsomedial peri-olivary nucleus; C = afferent axon of the medial trapezoid body, crossing the myelin sheaths of the abducens rootlet (6) and the dorsomedial peri-olivary nucleus to form the type of terminal arborization consistently associated with the dendrites of principal neurons; D = collateral of a calyciferous axon in the medial trapezoid nucleus, which ramifies in the dorsomedial periolivary nucleus; E = afferent axon, arborizing in this nucleus; F = collaterals of calyciferous axons, ending in the medial trapezoid nucleus; G = large solitary process of a calyx; H = short collaterals of a calyx; J = collateral growth cones. * = Axon of dorsomedial periolivary neuron. Rapid Golgi method. Modified from figure 9 in MOREsT [J968aJ. Downloaded by: Université René Descartes Paris 5 126.96.36.199 - 10/26/2017 3:33:57 AM 30 344 them would correspond to a frequency map on the dorsoventral axis of the nucleus and to a timing mechanism on the mediolateral axis. Evidently slight differences in the times at which signals arrive from the two sides can be critical in determining if the activity of the individual neurons is enhanced or suppressed [GALAMBOS et al., 1959]. The medial nucleus of the trapezoid body contains three varieties of neurons in the cat (fig. 3 B, C, D). A detailed description appears elsewhere [MOREST, 1968a]. The principal neurons are the most numerous, and perhaps the most interesting, since they receive the calyces of Held, the large synaptic endings ofaxons from the contralateral ventral cochlear nucleus that establish a point-to-point correspondence with the neurons of the medial trapezoid nucleus (fig. 3 A). The principal neurons and the calyces of the medial trapezoid nucleus maintain a special relationship with the neurons of the crossed olivo-cochlear bundle in the dorsomedial peri-olivary nucleus (fig. 3 E, F). The peri-olivary neurons receive endings of axonal branches from the principal neurons of the medial trapezoid nucleus. The calyciferous axons, contacting the principal neurons, also send side-branches to the dorsomedial olivo-cochlear neurons. In order to form a useful notion of the possible significance of this relationship, it is necessary to have a clear idea of the structure and function of the calyciform synapse. The calyces of Held are large axosomatic endings (fig. 4). They are probably the largest synaptic endings in the brain [see MOREST, 1968a]. The calyx is formed by thin, broad, petal-like expansions of the terminal axon. These terminal processes, much like the petals of a tulip, enclose a large portion of the cell body upon which they synapse. Normally each axon forms one, and only one, calyx ending on one, and only one, principal neuron. Each principal neuron receives only one calyx. Numerous, thin, local collaterals emanate from the calyces. These local collaterals form many small endings in association with the cell bodies of surrounding principal neurons, which also receive calyx endings. The principal neuron is a highly specialized and stereotyped variety of neuron, clearly distinguished from other types of neurons in the region by its typical cell body in Nissl-stained preparations and by its characteristic dendritic branching pattern in Golgi impregnations (fig. 4). The dendrites receive the endings ofaxons from the cochlear nucleus, other than the calyciferous fibers (fig. 4 C). But no other type of neuron receives calyces. This highly specific synaptic arrangement establishes a pointto-point, cell-to-cell correspondence between one portion of the ventral cochlear nucleus and the medial trapezoid nucleus. In electron micrographs it is possible to identify the synaptic contacts of Downloaded by: Université René Descartes Paris 5 188.8.131.52 - 10/26/2017 3:33:57 AM MOREST 345 Fig. 5. Electron micrograph of a portion of a principal cell from the medial trapezoid nucleus of a cat. NU = nucleolus; N = nucleus; NS = Nissl substance; M = mitochondria; L = lysosome; S = synaptic endings of afferent axons; * = synaptic complexes; A = myelinated axon; G = glial processes, Scale = 0.5,um. Downloaded by: Université René Descartes Paris 5 184.108.40.206 - 10/26/2017 3:33:57 AM Auditory Neurons of the Brain Stem Downloaded by: Université René Descartes Paris 5 220.127.116.11 - 10/26/2017 3:33:57 AM Fig. 6. Part of a calyx (C) ending on the cell body of a principal neuron (P). F = myelinated parts of calyx fibers; FM = central core of filaments and mitochondria in fiber endings; C' = part of another ending. Scale = 0.5 11m. .---.', , ';t~ ' . lj) , • '/< ~~ II . ' Fig. 7. Cross-section of the central stem of a calyx ending (F) in synaptic contact with a principal cell body (P) and also with an unidentified dendritic profile (D). F= bundles of calyx filaments; * = synaptic complexes. Scale = 0.5 fl-m. Downloaded by: Université René Descartes Paris 5 18.104.22.168 - 10/26/2017 3:33:57 AM ... I , ., 348 Fig. 8. Part of a calyx process (C) in contact with a principal cell body (P). In the thin section this calyx process extends for a length of 10 .urn. The external membrane of such an ending is separated from the adjacent cell membranes by intercellular spaces. This holds for the synaptic complexes (*) as well as the surface invaginations ( +). Although the pre- Downloaded by: Université René Descartes Paris 5 22.214.171.124 - 10/26/2017 3:33:57 AM MOREST Auditory Neurons of the Brain Stem 349 Fig. 9. Synaptic complex (*) of a principal cell body (P) with a calyx ending (C), which contains many clear vesicles and part of a mitochondrion (M). D = large densecored vesicles, associated with a multivesicular body; arrows = cisternae of endoplasmic reticulum. Scale = 0.5 ,um. and post-synaptic membranes may be sectioned tangentially (lower edge of the synaptic complex), so far, close junctions between them have not been observed. The surface invaginations often contain exceedingly thin processes (arrow) or their remnants, some of which probably derive from the filamentous astrocytic processes (G) encasing the synaptic endings. Evidently an elaborate network of these delicate processes extends over the surface of the principal cell between and beneath the calyx processes. This network often appears in rapid Golgi impregnations of these cells and other cells; it probably corresponds to the pericellular net of GOLGI , observed, illustrated, and variously interpreted by BETHE , HELD , and others [see RAM6N Y CAJAL, 1934]. Scale = 0.5,um. Downloaded by: Université René Descartes Paris 5 126.96.36.199 - 10/26/2017 3:33:57 AM the calyces in the cat by limiting the observations to cell bodies with the typical features of principal neurons [see MOREST, 1968a]. When this is done, the typical long, thin, petal-like profiles of the calyx endings are readily recognized (fig. 5-8). Many of the smaller synaptic profiles probably represent partial sections of calyx processes and the endings of local collaterals from neighboring calyces. The surface of the cell body is extensively covered with synaptic endings. In every profile of the principal cells so far observed, perhaps half of the surface is covered with synaptic endings. Here and there, thin, thready processes weave between the calyx and the perikaryal surface; sometimes such processes gather in strands or patches. Some of these processes are seen in continuity with astrocytic branches (fig. 8); perhaps others represent appendages of the calyces or the principal cell body. The large 350 central core of the calyx contains aggregates of neurofilaments (fig. 6 and 7). The synaptic complexes consist of numerous clear vesicles, thickened preand post-synaptic membranes, a prominent sub-synaptic density in the principal cell, and an intermediate density in the slightly-widened synaptic cleft (fig. 9). A number of small synaptic complexes may be found in each calyx profile (fig. 7 and 8). Since these complexes appear to be relatively uniform in size, it seems unlikely that many of them are connected to each other. Thus a single calyx ending apparently may form many synaptic contacts with the principal cell soma. This observation, together with the large surface area occupied by synaptic endings, suggests that the synaptic activity of the calyx would dominate the post-synaptic membrane. These are cytological features typically associated with chemical synapses in the nervous system. Similar findings have been reported in the rat [LENN and REESE, 1966]. Close junctions at the calyces of Held have not yet been demonstrated. Thus there is neither morphological nor electrophysiological evidence for electrical synapsis at the calyx of Held. However, intracellular recordings from the principal neurons remain to be made. The identity of the chemical transmitter at the calyx of Held is not known. Evidently acetylcholinesterase activity has not been localized in the calyces, as it has in the olivo-cochlear bundle and in the cell bodies of the dorsomedial and other peri-olivary neurons forming that bundle [RASMUSSEN, 1964; OSEN and ROTH, 1969]. In collaborative studies with GUINAN [1968 and unpublished], we have identified the principal neuron with a particular type of unit activity recorded with microelectrodes in the medial trapezoid nucleus. Not surprisingly this unit has a narrow tuning curve. A tonotopic arrangement in the nucleus is suggested by the sequences of these units' best frequencies [GUINAN et al., 1969]. Possibly this sequence in the adult cat corresponds to the dorsal-toventral, or perhaps, more accurately, dorsolateral-to-ventromedial, sequence, deduced from the laminar arrangement of the peri-dendritic plexus in the newborn kitten (fig. 10) [MOREST, 1968a]. The combined anatomical and electrophysiological data [MOREST, 1968 a; GUINAN, 1968; GUINAN et al., 1969; LI and GUINAN, 1971] suggest that the principal neurons and their calyces exhibit spontaneous activity and, in response to simple acoustic stimuli (tone bursts or clicks), produce characteristic temporal response patterns with very short latencies, as shown by extracellular micro electrode recordings. In the above respects, these units closely resemble the auditory nerve fibers [KIANG et al., 1965b]. However, the potentials of the calyx units are associated with a complex wave form. The complex wave consists of an early positive potential, which is apparently generated by the calyx itself, Downloaded by: Université René Descartes Paris 5 188.8.131.52 - 10/26/2017 3:33:57 AM MOREST Auditory Neurons of the Brain Stem 1 100 iJ 351 m ~ y Fig. 10. The tonotopic correspondence between the medial superior olivary, medial trapezoid, and dorsomedial peri-olivary nuclei, as seen in the transverse plane from a newborn cat. X, Y, and Z = axons of the medial trapezoid body, projecting to the medial region of the medial superior olivary nucleus (MSO) in a dorsoventral tonotopic sequence, contribute collaterals to the peri-dendritic plexus of the medial trapezoid nucleus, also in a nearly dorsoventral sequence. The basal tum of the cochlea is represented most ventrally. A, B, and C = the main axons of principal neurons in the medial trapezoid nucleus, before leaving the section laterally, send collaterals, a, b, and c, to the dorsomedial peri-olivary nucleus, so that the dorsal-to-ventral extent of the first nucleus is projected across the lateral-to-medial axis of the second. The large calyx fibers ending next to the principal neurons and their long collaterals to the dorsomedial peri-olivary nucleus respect the topographical correspondence as indicated. The cells corresponding to B, b, and C, c were taken from adjacent sections but retain their relative positions in the drawing. The scale at the upper left is parallel to the median raphe. P = pyramid. Rapid Goigi method. Modified from figure 10 in MOREST [1968a). Downloaded by: Université René Descartes Paris 5 184.108.40.206 - 10/26/2017 3:33:57 AM z 352 whereas a later, negative potential corresponds to a post-synaptic event, perhaps in the initial segment of the principal neuron. Since both components of the wave nearly always occur together, at least with simple acoustic stimuli, it is probable that nearly every signal invading a calyx will cause the post-synaptic principal neuron to fire and that the synapse is excitatory conclusions in harmony with the cytological features of the calyciform synapse. The effects of the calycine collaterals on surrounding cells are not known. Even if the calyx forms an excitatory synapse, the collaterals could elicit either excitatory or inhibitory post-synaptic responses, depending on the properties of the post-synaptic membranes. If inhibitory, the local collaterals of the calyx could produce an inhibitory surround, which might influence the shapes of the units' tuning curves or the temporal patterns of their discharge. The dorsomedial peri-olivary nucleus receives the long collaterals of the calyx fibers and of the principal meurons and other afferents, coming directly from the cochlear nuclei. These afferent axonal endings are arranged in more or less vertical layers, in parallel with elongate neurons - a pattern that we have learned to associate with a topographic organization. The axonal collaterals of both the calyx fibers and of the principal neurons project into these layers in an orderly sequence (fig. 4). The result is that a rigid correspondence obtains between sectors of the medial trapezoid nucleus and the layers of the dorsomedial peri-olivary nucleus. Insofar as this correspondence correlates with the frequency organization of the auditory system in this region, we may deduce the probable tonotopic sequence as follows: The dendrites of the principal neurons engage an elaborate plexus of axonal endings (fig. 4). These afferent axons arborize in a pattern that recapitulates that of the dendritic branches on which they end. The arbors of the peri-dendritic plexus are flattened in nearly horizontal planes, and their arrangement forms a lamination pattern in the medial trapezoid nucleus (fig. 10). This laminar pattern probably corresponds to the tonotopic organization of the nucleus. Much of the peri-dendritic plexus derives from collaterals ofaxons passing through the medial trapezoid nucleus en route from the cochlear nucleus to the medial superior olive. Since we know that the afferent axons of the medial superior olive are tonotopically arranged in a dorso-ventral sequence, the layers of the peri-dendritic plexus in the medial trapezoid nucleus must also maintain a corresponding dorsolateral-to-ventromedial, low-to-high frequency, tonotopic sequence. It seems likely that the tonotopic arrangement of the calyces would also follow this pattern. The Downloaded by: Université René Descartes Paris 5 220.127.116.11 - 10/26/2017 3:33:57 AM MOREST 353 more medial and dorsal principal neurons send long axonal collaterals to the more medial and ventral layers of the dorsomedial peri-olivary nucleus, and the long collaterals of the calyces also conform to this pattern. From this we may infer that a tonotopic sequence occurs across the mediolateral axis of this nucleus, such that the lower frequencies are represented more medially. It might be expected that this frequency organization would correspond to the range of tuning curves already shown among units in the crossed olivocochlear bundle [FEx, 1962]. A systematic exploration of unit electrical activity in the peri-olivary origins of the olivo-cochlear bundle remains to be done. The possible significance of the long collaterals projecting to the dorsomedial olivo-cochlear neurons is now open for exploration. One consequence of the arrangement of the collaterals is that the neurons of the olivo-cochlear bundle would be in a position to sample both the input and output of the principal neurons. If the olivo-cochlear bundle forms part of a feedback loop [FEx, 1962], it could function in a physiological automatic gain control of the auditory signals relayed by the cochlear nucleus. In that case the collaterals of the calyx fibers could negotiate an increase in the activity of the crossed olivo-cochlear neurons, in response to increased sound levels and the accompanying increased afferent fiber activity. In the case of a physiological control system it may be just as important to monitor the output of central neurons in response to input alterations as it is to monitor the change of input itself. In this context the specific pattern of the collaterals just described may possibly have some significance, since these collaterals should permit the dorsomedial olivo-cochlear neurons to sample the input to the principal neurons by way of the calyx collaterals and the output of the principal neurons by way of the principal axonal collaterals. But, since the probability of synaptic transmission is so high at the calyciform synapse, it is difficult to see what new information could be transmitted in this way. Nevertheless, the input from the cochlear nucleus by way of the peri-dendritic plexus could playa significant role in the output of the principal neurons. When the level of activity in the calyx fibers is high, it seems unlikely that the post-synaptic potentials initiated by the peri-dendritic plexus could influence the firing pattern of the principal neurons very much. However, when the calyx activity is slow enough, as with low sound levels perhaps, then the synaptic activity of the peri-dendritic plexus might well influence the time-pattern of response greatly enough to be reflected, by way of the collaterals, as a change in the level of excitation of the olivo-cochlear neurons. In other words, it seems possible that the special anatomical constellation defined here could Downloaded by: Université René Descartes Paris 5 18.104.22.168 - 10/26/2017 3:33:57 AM Auditory Neurons of the Brain Stem MOREST 354 provide for a differential pattern of response in the olivo-cochlear bundle, depending both on the stimulus level and on the relative activity in different parts of the cochlear nucleus and the auditory system. Discussion It is not possible to explain the function of any of the central auditory neurons at present in the cat, not to mention the human. Nevertheless, two lessons might be drawn from the present analysis for the purpose of this symposium. First, it should be evident that certain morphological attributes of the central auditory neurons are essential to a definitive explication of central auditory function. Electrophysiological studies alone cannot explain function. Morphological factors that seem to hold great promise for elucidating the physiology of the auditory system include the geometrical arrangements of the axons and dendrites making synaptic contacts and the sequential patterns of the synaptic connections. The second point concerns the lack of information on the functions of auditory neurons in the human. Since it is unlikely that the necessary electrophysiological correlations with the morphology can be made directly in humans, as in cats, we may have to rely primarily on microscopical observations of the homologous structures in autopsy specimens to clarify the normal and pathological processes in the auditory system of man. The relevant anatomical studies in the human remain to be done. The current analyses in the cat hopefully provide a basis for the first steps in that direction. Morphological features of auditory neurons that define their physiological capacities are the spatial arrangement of the axons and dendrites and the sequences of the synaptic connections of these processes. In the medial superior olive the spatial arrangement of dendrites and afferent axons would allow for a tonotopic arrangement in one axis of the nucleus, while in the other axis the sequence of connections would permit binaural interactions. In the medial trapezoid nucleus and the dorsomedial peri-olivary nucleus the spatial arrangement of the axonal calyces of Held and the peri-dendritic axonal plexus, together with their collaterals, may establish a tonotopic correspondence between these nuclei, the cochlear nucleus and the medial superior olive, and the crossed olivo-cochlear bundle. The sequences of synaptic connections elaborated by these axonal coIIaterals may permit the olivo-cochlear bundle to adjust its level of activity as a function of changing Downloaded by: Université René Descartes Paris 5 22.214.171.124 - 10/26/2017 3:33:57 AM Summary Auditory Neurons of the Brain Stem 355 inputs and outputs of the medial trapezoid neurons. The approach developed in this study holds promise of fruitful application to the human auditory system. BETHE, A.: Uber die Neurofibrillen in den Ganglienzellen von Wirbelthieren und ihre Beziehungen zu den Golginetzen. Arch. mikr. Anat. 55: 513-558 (1900). FEx, J.: Auditory activity in centrifugal and centripetal cochlear fibers in cat. A study of a feedback system. Acta physiol. scand. 55: suppl. 189, pp. 1-68 (1962). GALAMBOS, R.; SCHWARTZKOPFF, J., and RUPERT, A.: Micro-electrode study of superior olivary nuclei. Amer. J. Physiol. 197: 527-536 (1959). GOLGI, C.: Intorno alia struttura delle cellule nervose; in Opera omnia, vol. 2, pp. 643-653 (Hoepli, Milano 1903). GUINAN, J.J., jr.: Firing patterns and locations of single auditory neurons in the brain stem (superior olivary complex) of anesthetized cats; diss. Massachusetts Institute of Technology, Cambridge (1968). GUINAN, J.J., jr.; GUINAN, S.S., and NORRIS, B.E.: Single auditory units recorded in the medial nucleus of the trapezoid body (MNTB) of anesthetized cats. J. acoust. Soc. Amer.46: 113 (1969). HELD, H.: Uber den Bau der grauen und weissen Substanz. Arch. Anat. Physiol. (anat. Abt.) 189-224 (1902). KIANG, N.Y.S.; PFEIFFER, R.R.; WARR, W.B., and BACKUS, A.S.N.: Stimulus coding in the cochlear nucleus. Ann. Otol. Rhinol. Laryng., St. Louis 74: 463-485 (1965a). KIANG, N.Y.S.; WATANABE, T.; THOMAS, E.C., and CLARK, L.F.: Discharge patterns of single fibers in the cat's auditory nerve; MIT Research Monograph No. 35 (MIT Press, Cambridge, Mass. 1965b). LENN, N.J. and REESE, T.S.: The fine structure of nerve endings in the nucleus of the trapezoid body and the ventral cochlear nucleus. Amer. J. Anat. 118: 375-389 (1966). LJ, R. Y-S. and GUINAN, J.J., jr.: Antidromic and orthodromic stimulation of neurons receiving calyces of Held. Quarterly Progress Report No. 100, pp. 227-234 (Research Laboratory of Electronics, Massachusetts Institute of Technology, 1971). LORENTE DE N6, R.: Anatomy of the eighth nerve. III. General plan of structure of the primary cochlear nuclei. Laryngoscope 43: 327-350 (1933). MOREST, D.K.: The neuronal architecture of the medial geniculate body of the cat. J. Anat., Lond. 98: 611-630 (1964a). MOREsT, D.K.: The laminar structure of the inferior colliculus of the cat. Anat. Rec. 148: 314 (1964b). MOREsT, D.K.: The probable significance of synaptic and dendritic patterns of the thalamic and midbrain auditory system. Anat. Rec. 148: 390-391 (1964c). MOREST, D.K.: The laminar structure of the medial geniculate body of the cat. J. Anat., Lond. 99: 143-160 (1965a). MOREsT, D.K.: The lateral tegmental system of the midbrain and the medial geniculate body: study with Golgi and Nauta methods in cat. J. Anat., Lond. 99: 611-634 (1965b). Downloaded by: Université René Descartes Paris 5 126.96.36.199 - 10/26/2017 3:33:57 AM References MOREST 356 Author's address: D.K. MOREST, Department of Anatomy, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 (USA) Downloaded by: Université René Descartes Paris 5 188.8.131.52 - 10/26/2017 3:33:57 AM MOREST, D.K.: The collateral system of the medial nucleus of the trapezoid body of the cat, its neuronal architecture and relation to the olivo-cochlear bundle. Brain Res. 9: 288-311 (1968a). MOREST, D.K.: The growth of synaptic endings in the mammalian brain: a study of the calyces of the trapezoid body of the cat. Z. Anat. EntwGesch. 127: 201-220 (1968b). MOREST, D.K.: Dendrodendritic synapses of cells that have axons: the fine structure of the Golgi type II cell in the medial geniculate body of the cat. Z. Anat. EntwGesch. 133: 216-246 (1971). MOREST, D.K. and MOREST, R.R.: Perfusion-fixation of the brain with chrome-osmium solutions of the rapid Golgi method. Amer. J. Anat.118: 811-832 (1966). OSEN, K.K. and ROTH, K.: Histochemical localization of cholinesterases in the cochlear nuclei of the cat, with notes on the origin of acetylcholinesterase-positive afferents and the superior olive. Brain Res. 16: 165-184 (1969). RAM6N Y CAJAL, S.: Les preuves objectives de I'unite anatomique des cellules nerveuses. Trab. Inst. Cajal Invest. bioI. 29: 1-137 (1934). RASMUSSEN, G.L.: The superior olivary peduncle and other fiber projections of the superior olivary complex. J. compo Neurol. 84: 141-220 (1946). RASMUSSEN, G.L.: Anatomic relationships of the ascending and descending auditory systems; in FIELDS and ALFORD Neurological aspects of auditory and vestibular disorders, pp. 1-19 (Thomas, Springfield 1964). RASMUSSEN, G.L.; GACEK, R.R.; MCCRANE, E.P., and BAKER, C.c.: Model of cochlear nucleus (cat) displaying its afferent and efferent connections. Anat. Rec. 136: 344 (1960). ROSE, J.E.; GREENWOOD, D.D.; GOLDBERG, J.M., and HIND, J.E.: Some discharge characteristics of single neurons in the inferior colliculus of the cat. 1. Tonotopical organization, relation of spike-counts to tone intensity, and firing patterns of single elements. J. Neurophysiol. 26: 294-320 (1963). STOTLER, W.A.: An experimental study of the cells and connections of the superior olivary complex of the cat. J. compo Neurol. 98: 401-431 (1953). WARR, W.B.: Fiber degeneration following lesions in the anterior ventral cochlear nucleus of the cat. Exp. Neurol. 14: 453-474 (1966). WOOLSEY, C.N. and WALZL, E.M.: Topical projection of nerve fibers from local regions of the cochlea to the cerebral cortex of the cat. Johns Hopk. Hosp. Bull. 71: 315-344 (1942).