Auditory Pathway of the Epileptic Waltzing Mouse I

Auditory Pathway of the Epileptic Waltzing Mouse I. A COMPARISON OF THE ACOUSTIC PATHWAYS OF THE NORMAL MOUSE WITH THOSE OF THE TOTALLY DEAF EPILEPTIC WALTZER

MURIEL D. ROSS Department of Anatomy, Medical Center, University of Michigan, Ann Arbor, Michigan

Waltzing and epilepsy are hereditary cisms of this paper, and to Dr. Edward traits which appear independently or to- Lauer for his suggestions and his assist- gether in various stocks of mice of the ance in matters of technique. She is also genus Peromyscus. They are inherited in grateful to Dr. Lee R. Dice and the Labo- general as Mendelian recessives (Dice, '35; ratory of Vertebrate Biology for making Watson, '39 j. Young members of the par- the mice and the testing equipment avail- ticular stock of Peromyscus rnnniculatus able to her for this study, and to Dr. Eliza- artemisiae to be described in this study ex- beth Barto, who tested the mice for range hibit both waltzing and epilepsy when of hearing. Assistance was obtained from stimulated by sounds of various kinds. a grant from the Alfonso Morton Clover At the sound of jingling keys, or of certain Scholarship and Research Fund to the pure tones, the young epileptic waltzer Laboratory of Comparative Neurology for whirls in circles and then dashes wildly the preparation of the material for micro- about the enclosure. After a few seconds, scopic examination. Aid in testing the he falls upon his side in an epileptic responses of the experimental animals seizure. His body becomes rigid, his fore- used in this study was supplied through legs are flexed and his hind legs are ex- a grant (MH 375 j to Dr. Lee R. Dice from tended. The animal resumes his circus the National Institute of Mental Health, movements after recovering from the seiz- of the National Institutes of Health, Pub- ure but whirls in a graceful manner, not lic Health Service. wildly as before. As the mouse grows older, it is more and more difficult to in- MATERIALS AND METHODS duce the waltzing and epileptic attack. A total of 26 animals was obtained from Finally, the animal appears to become the Laboratory of Vertebrate Biology for deaf, for he gives no visible sign that he use in this study. Of this number eight hears the sound stimulus. His ears do not animals were normal controls taken from a twitch and he shows no uneasiness. stock of Peromyscus maniculatus blandus This study represents an attempt to as- from Tularosa, New Mexico. They showed sess possible nervous system changes re- neither waltzing nor convulsive behavior lated to the loss of hearing exhibited by when exposed to the stimulus of jingling these mice. In Part I of this report, the keys for 90 seconds. The rest of the ani- central relations of the auditory systems mals were epileptic waltzers, hybrids be- in older, deaf epileptic waltzers will be tween several subspecies of mice. Nine of compared with those in normal controls the epileptic waltzers were considered deaf of the genus Peromyscus. The auditory because they did not twitch their ears in centers of young, partially deaf, epileptic response to a tap on glass, to a squeak, or waltzing mice will be considered separately to keys jingling, and the last procedure did in Part 11. not cause waltzing or a seizure. Six ani- The author is deeply indebted to Dr. mals were young, possessed acute hearing, Elizabeth C. Crosby €or her helpful criti- and both waltzed and had a convulsive

317 318 MURIEL D. ROSS scizure when exposed to the sound of the medulla oblongata dorsolateral to the resti- jingling keys. Three animals had less form body. The posterior end of the acute hearing than the young mice; they tubercle lies at the level of the lateral re- suffered less violent reactions to key jin- cesses of the fourth ventricle. As it is gling, as evidenced by a weak dash or ear followed forward, the dorsal cochlear nu- twitching. One deaf and one young mouse cleus increases in size ventrolaterally and, died of natural causes, leaving 24 animals to a lesser degree, in thickness, reaching which were actually prepared for study. its greatest development in its middle At the end of the experimental testing, third. In these sections it lies dorsolateral all of the animals were sacrificed and per- to the ventral cochlear nucleus and to the fused. Seventeen of these animals were restiform body. Rostra1 to a plane through perfused with 10% formalin; seven with a the caudal part of the genu of VII, the dor- special modification of the Zenker-formol sal cochlear nucleus shortens dorsoven- solution described by Guild ('19). Then, trally and gradually flattens into a narrow the skull cap was opened and the lower band of granular cells which still covers jaw and muscles of the head were cut off. the dorsolateral surface of the ventral The brains were allowed to harden in situ cochlear nucleus. Both ventral and dorsal in 10% formalin for several days and then cochlear nuclei extend rostrally to a plane the temporal bones and/or the brains were through the motor nucleus of the trigemi- removed. nal nerve. None of the cochleae were suitable for The internal organization of the acous- study and will not be considered further tic tubercle differs at various levels. Cau- here. Of the 16 brains which were re- dally, it is composed of a few delicate moved, three were fixed, cleared, and em- fibers and numerous cells; the latter are bedded according to the Huber-Guild pyri- either small in size, fusiform or round, dine-silver method. The tissue became and darkly staining, or they are of me- very hard and shattered when cut at a dium-size, spherical and pale staining. No thickness of 20 p. The 13 remaining pattern of distribution of the cells or of brains were fixed, cleared, and embedded the fibers is observed at this level. As the in paraffin according to the usual methods. acoustic tubercle broadens, the fibers with- Seven paraffin blocks were cut on a rotary in it become thicker and more numerous microtome in sections 25 LI thick, mounted and the cells increase in number. A dis- serially, and stained after the Weil method tinct lamination of the tubercle, involving for fibers. Two brains were cut at 15 cr, both the cells and the fibers, begins at the mounted in serial sections, and stained level of the facial nucleus and ends ros- with cresyl-echt-violet. The remaining four trally in sections through the genu and brains were cut at 25 u, mounted serially, roots of VII. The distance between the and stained with toluidin blue. All of the caudal pole of the acoustic tubercle and brains were cut transversely. the onset of lamination within it is very The first part of this report is based upon short. a study of the acoustic pathway in four Among the observers who have de- series of brains. Brain no. 87932 (nor- scribed the lamination of the acoustic mal, female) and brain no. 85842 (deaf, tubercle in mammals are Ram6n y Cajal female) were stained according to the ('09), Winkler and Potter ('11, '14), and, Weil method. Brain no. 87120 (normal, more recently, Lorente de N6 ('33). Each male) and brain no. 85836 (deaf, male) of the these workers recognized four were stained with cresyl-echt-violet. fundamental layers, although the laminae described by each include different DESCRIPTION OF THE NORMAL MATERIAL elements and the nomenclature varies. Lorente de N6, working with Golgi prepa- Primary auditory centers rations of mouse and cat brains, sub- Dorsal cochlear nucleus. The acoustic divided the acoustic tubercle still further. tubercle of the mouse (figs. 1, 2, 3) is In addition to the four laminae, he found comparable with the dorsal cochlear nu- several other distinct areas. In the pri- cleus of higher forms. It is located in the mary acoustic nuclei as a group, he de- NORMAL AND ABNORMAL AUDITORY PATH 319 fined at least 13 different regions and 40 toward the midline as dorsal secondary to 50 types of neurons. cochlear fibers. In the acoustic tubercle of the mouse In addition to the lamination just de- material studied for this paper, four layers scribed, some authors have recognized fur- are distinguishable lying in a lateromedial ther cell groupings within the acoustic direction; these will be described from the tubercle. Thus, Winkler and Potter have surface toward the restiform body. The described a nucleus proprius, which rep- most superficial lamina, Layer I, is poor resents the central unlaminated core of in fibers and cells (fig. 2). Beneath the the tubercle. In mouse brain no. 87120, pia there are small, round or fusiform, stained for cells, nucleus proprius begins dark staining cells intermingled with in sections at the level of the facial nu- others medium in size, round or ovoid, and cleus, just caudal to the beginning of lami- pale staining. This lamina I corresponds nation of the acoustic tubercle. Some of to both the surface (“epithelial”) and the its cells can be traced rostrally to sections “superficial plexiform” layers of Itam6n y through the caudal end of the gem of VII. Cajal, and to the “stratum griseum super- At this level, with an increase of similar ficiale” of Winkler and Potter (’11). cells within the rest of the acoustic tu- Winkler and Potter employed “lamina bercle, the nucleus proprius can no longer cellularis” for the second layer, which is be distinguished. rich in cells as the terminology suggests. Nucleus proprius (figs. 1, 2, 3) varies This lamina is Ram6n y Cajal’s “zone of considerably in size from level to level, granule and large fusiform cells.” Layer but small, round, dark staining cells arc I1 (fig. 2) is especially characterized in present throughout. They were called the mouse by the presence of spindle- “grains” by Winkler and Potter (’11, ’14), shaped cells, which generally lie with their and are closely grouped together. Most long axes at right angles to the surface caudally these “grains” spread in a thin of the acoustic tubercle. These cells are layer across the ventromedial two thirds small or of medium-size in the mouse and of the acoustic tubercle. Initially the cells vary in their staining quality; mingled do not attain the most ventral portion of with them are many small, dark, round the dorsal cochlear nucleus, but do come cells. to this area shortly. Nucleus proprius Within the third layer (fig. 2) poly- reaches its greatest size, occupying most morphous neurons are arranged between of the ventral fourth of the acoustic tu- numerous diagonally cut fibers. The fibers bercle, in sections in the plane of the cau- are, for the most part, of two derivations: dal pole of the ventral cochlear nucleus. some of them are cochlear nerve fibers on As the cells of the ventral cochlear nucleus their way to the cells of the dorsal cochlear increase in number ventralward, they di- nucleus where they terminate; others have vide nucleus proprius into a lateral and their origin within the latter nucleus and a medial portion. The medial portion is are the axons of secondary neurons which smaller and ends within 60 N. The dorsal ascend to higher levels. This layer corre- portion becomes reduced in size but can be sponds to Winkler and Potter’s (’14) “stra- traced to the oral limit of the nucleus. The tum medullare superficiale,” and to Ram6n fiber content within nucleus proprius is y Cajal’s “deep plexiform layer” or “zone never great; delicate fibrils ramify between of large nerve cells.” the closely arranged cells. The deepest layer of the acoustic tu- Ventral cochlear nuck?us. The ventral bercle (fig. 2), the “stratum medullare pro- cochlear nucleus (figs. 2, 3) does not ex- fundum” of WinMer and Potter, is com- tend so far caudalward as does the acous- posed of cochlear nerve fibers, which enter tic tubercle. It begins at the level of the it ventrally, and of the axons of the prev- facial nucleus and ends rostralward at iously mentioned secondary neurons which the level of the motor nucleus of the tri- are gathering into a heavy bundle medi- geminal nerve. Ram6n y Cajal (’09, ’11) ally. This bundle of fibers emerges dor- and Lorente de N6 (’33) have described somedially from Layer IV and then swings various zones in this nucleus. According dorsalward over the restiform body and to Ram6n y Cajal it has two parts, an an- 320 MURIEL D. ROSS terior or rostral portion and a posterior is not evident in the ventral cochlear nu- or caudal portion. This division is based cleus of these mice. A layer of flattened upon the presence of a “tail“ or dorsal ex- pial cells covers the nucleus except in the tension of the ventral cochlear nucleus “tail.” Internal to this lamina, a thin layer which lies internal to the caudal part of of dark, closely arranged, granular cells the acoustic tubercle. Four zones were is observed. These cells are directly con- described by Ram& y Cajal for the ven- tinuous with the granules observed in nu- tral part of the ventral cochlear nucleus, cleus proprius and in the anterior end of but they were not present in the dorsal the acoustic tubercle; they are not present extension or in the anterior levels of the along the dorsolateral border of the ven- nucleus. These zones were named in tral cochlear nucleus caudal to the level lateromedial order: (1) an “epithelial of the superior olive. Medial to the layer layer”; (2) a superficial plexiform zone; of the granule cells, and in the so-called (3) a zone of small cells; (4) a zone of “tail” of the nucleus, are the neurons and large cells and of fiber bundles. This de- fibers which make up the bulk of the scription of the lamination was based ventral cochlear nucleus. The most promi- upon his preparations of the cat, the rab- nent of these neurons are large, triangular bit, and the guinea pig. Lorente de N6 or oval in shape, and have large, oval (’33) divided the ventral cochlear nucleus nuclei; their cytoplasm takes on a very of the mouse and cat in the dorsoventral characteristic violet color in the cresyl direction into regions I, I1 and 111. violet material. Smaller, round and fusi- In the mouse brains reported here a form cells are intermingled with the large division into rostral and caudal portions neurons. Rostrally, as the nucleus becomes has been made. The caudal subdivision ffat, the cells located dorsally are chiefly (fig. 2) begins as a few cells lying ven- oval in shape and are closely grouped; tromedial to the tubercle, but increases those found ventrally are mostly triangular rapidly in size to form a rounded hillock. or spindle-shaped. These cells in the ros- The dorsal slope of the hillock is extended tral portion of the ventral cochlear nucleus dorsally so that it lies medial to the acous- are, on the whole, smaller, more numer- tic tubercle and lateral to the restiform ous, and more densely arranged than in body. This dorsal portion is lengthened the caudal part of this nuclear complex. in such a fashion in the two mouse brains The cells in the caudal portion of the studied and corresponds to the dorsal ex- ventral cochlear nucleus are divided into tension or “tail“ described by Ram6n Y several rows by layers of longitudinally Cajal. In planes through the caudal part running fibers. The layers of fibers ap- of the genu of VII, the dorsal slope of the proximate each other more and more to- ventral cochlear nucleus rounds consider- ward the middle of the nucleus, as the ably (fig. 3) and such a “tail” is no longer level of the cochlear nerve is approached. observed. With the disappearance of the Here, the ventral cochlear nucleus is di- dorsal extension, the caudal subdivision vided into a lateral and a medial zone by ends and the rostral portion begins. This the thick bundle of cochlear nerve fibers latter subdivision extends forward to the and a small group of cells is situated dorso- level of the motor nucleus of the trigemi- medially between the fascicles. In these rial; caudally it is rounded in outline (fig. lateral and medial zones, the fibers form 3) but, at the level of the vestibular nerve, a network among the cells. The cochlear the hillock shortens and the lateral surface nerve enters the ventral cochlear nucleus of the nucleus soon flattens. The entire ventromedially at the level of the roots of nucleus diminishes in size very gradually VII, occupying almost all of the ventral in such a way that, rostrally, it is narrower and medial parts of the nucleus. Here, dorsally than ventrally. Its lateral surface only the dorsolateral area exhibits numer- is rather straight and its ventral border ous cells and ramifying fibers. Rostra1 to slopes gently. this level, the nucleus is again divided by Such a high degree of organization of a layer of fibers and lateral and medial cells and fibers into a definite pattern as zones can be distinguished. Most rostrally, was described for the acoustic tubercle the fibers are evenly distributed in the NORMAL AND ABNORMAL AUDITORY PATH 321 ventral cochlear nucleus and no subdivi- cleus of the lateral lemniscus, to which sions are found. it is joined caudally by a few strands of cells. The main mass of the nucleus lies Secondary auditory centers in a dorsolateral position ventral to the and connections inferior colliculus. Its cells are large and Nuclear complex of the superior olive. fusiform or ovoid in shape; many of them The superior olive is a folded gray mass lie with their long axes in a horizontal extending between the levels of the facial plane. nucleus caudally and those of the motor Within these inferior and superior nu- trigeminal nucleus rostrally. Its cells are clei are numerous fibrils and heavy bun- of medium-size and of polygonal or fusi- dles of fibers connect the inferior nucleus form shape; their long axes generally fol- and the dorsal part of the superior nu- low the curves of the nucleus. Internal to cleus. The fibers separate the ventral cells the superior olive, and closely associated of the latter nucleus into strand-like for- with it, lies the medial accessory olive. mations; these strands caudally provide This nucleus is somewhat semilunar in a continuity between the two nuclei of outline, although it is much less definite the lateral lemniscus. These heavy fas- in contour in the mouse than in some other cicles may be regarded as internuclear forms. Its cells are also of medium-size components of the lateral lemniscus. and of fusiform or polygonal shape. Inferim colliculus. In the mouse, as in Associated with the superior olive (and other mammals, the inferior colliculus con- with the trapezoid body) are two small nu- sists of two portions - a central nuclear clear masses, the internal and extcrnal par- mass and a peripheral capsular part (fig. olivary nuclei. They lie between the fibers 7). The cells of the central nucleus are of the trapezoid body, ventral and ventro- rather large and polygonal in shape. At its lateral to the superior olive, respectively. periphery lies the capsular area consisting The cells of these parolivary nuclei are of fibers intermingled with rows of cells. spindle-shaped; they are slightly smaller Among the fibers are scattered small or in the external than in the internal par- medium-sized cells which are fusiform or olivary nucleus. In both cases the cells are polygonal in shape. smaller than those in the superior olive. The fibers of the lateral lemniscus as- Medial to the superior olive and lateral cending to the inferior colliculus enter the to the medial lemniscus lies an aggrega- central nuclear mass through the capsule tion of cells called the nucleus of the trape- (fig. 7). Most of the axons of the large zoid body. Its ovoid or polygonal cells are cells of the central nucleus collect ventro- more closely arranged and smaller than laterally to the central nucleus within the those in the medial accessory olive. capsule to enter the peduncle of the in- Nucleus of the lateral leminiscus. Two ferior colliculus (Held, 1893; Ram6n y nuclear masses are intercalated in the Cajal, '11; and others). Ram6n y Cajal course of the lateral lemniscus, the su- also believed that some of the smaller perior and inferior nuclei of this lemniscus cells of the capsule send their axons to (fig. 7). The inferior nucleus extends the medial geniculate nucleus. This pe- rostralward from upper pontine levels to duncle interconnects the inferior collicu- the plane of the caudal end of the inferior lus and the medial geniculate nucleus and colliculus. Caudally, it lies internal to the presumably also carries corticocollicular brachium pontis and rostrally, it is con- fibers (Crosby and Henderson, '48). tinuous with the more ventral portion of Medial geniculate nucleus. The medial the superior nucleus of the lateral lem- geniculate nucleus appears caudally as a niscus. The cells of this inferior nucleus small, oval shaped mass on each lateral are large, polygonal, and closely arranged. surface of the midbrain at the level of the In sections through the inferior collic- superior colliculus (fig. 9). In its caudal ulus, there is a loosely organized and elon- two thirds it lies posterior to the lateral gated cellular aggregation, the superior geniculate nucleus; its rostral portion is nucleus of the lateral lemniscus. This medial and slightly ventral to this latter nucleus is dorsolateral to the inferior nu- nucleus. The rostral tip of the medial 322 MURIEL D. ROSS geniculate nucleus tapers off into a small ules. These cells are continued into the group of cells situated in relation to the dorsal part of the lateral geniculate nu- external medullary lamina ventrally, the cleus and, more rostrally, occupy the posi- ventral nucleus of the thalamus medially, tion formerly taken by the dorsal portion the posterior portion of the lateral nucleus of pars principalis. In sections through of the thalamus dorsally, and the lateral the anterior part of the Edinger-Westphal geniculate body laterally and dorsolaterally. nucleus, the cells typical of the dorsal These cells merge with those of the ventral group of pars principalis disappear, the nucleus of the thalamus at levels through last few being located dorsolaterally with- the anterior half of the posterior commis- in the medial geniculate nucleus. On the sure. basis of cell types, rather than position in Many investigators have described this space, the group of cells appears to be nucleus in mammals (Ram6n y Cajal, '09, distinct, just as Ram611 y Cajal ('09) de- in the cat, guinea pig and mouse; Winkler scribed it in his mouse specimens. It does and Potter, '11, '14, in the rabbit and cat; not appear to be continuous with the pars Gurdjian, '27, in the rat; Rioch, '29, in posterior of the lateral nucleus of the thal- carnivores; Le Gros Clark, '30, '33, in amus as Le Gros Clark ('33) believed. Tarsius and insectivores; and Vogt, '09, The ventral group of pars principalis Malone, '10, Walker, '37, '38, and many corresponds to Ram6n y Caj al's inferior others in primates). Subdivisions have lobe of the medial geniculate nucleus. It been described by several of these workers, extends the entire caudorostral length of although there is disagreement as to the this nucleus and may be subdivided into functional (or even anatomical) signifi- at least three portions; the chief mass, cance of such secondary areas. the lateral part, and the ventral part. The Several regions are present in the nie- chief or central mass of pars principalis dial geniculate body of the mouse. The consists of cells of medium-size and of two major subdivisions are the pars prin- oval, triangular, or fuifoim shape; they cipalis and the pars magnocell.ulnris, as possess large, oval, pale staining nuclei the areas have been named by Rioch ('29). and a cytoplasm which takes a pale violet Pars principalis is the larger and more lat- stain with cresyl violet. In the central eral division and extends the entire caudo- mass the cells are arranged in small rostral length of the nucleus. In its middle groups but are generally close to one an- third it attains its greatest size and has a other. This part, which corresponds to bean-shape. Pars principalis can be sub- area "a" of Winkler and Patter ('11, '14), divided further into a series of groups of and to noyau interne of Ramdn y Cajal cells or zones, of which the dorsal and ('09), extends from the posterior tip to ventral are the two major groups. the anterior pole of the nucleus. In sec- The dorsal group is characterized by tions through the caudal part of the mam- cells which, on the whole, are of medium- millary bodies, the more dorsal cells of size, although they tend to be somewhat this portion of pars principalis grade over smaller rostrally than caudally. Their cell into the cells of the posterior part of the bodies are triangular or spindle-shaped. lateral nucleus of the thalamus. In this These cells stain more darkly and are more region of continuity the cells are small and loosely arranged than are those of the spindle-shaped or round, or are of medium- ventral portion. The dorsal group begins size and triangular or polygonal in shape. in the posterior fifth of the medial genicu- More rostrally, the cells located ventrally late nucleus as a cap of cells over the within the main mass of pars principalis ventral portion of pars principalis. In are not sharply delimited from those of more rostral sections, it assumes a dorso- the ventral nucleus of the dorsal thalamus. lateral position in relation to the ventral Gurdjian ('27) describes a similar contin- yroup and, along its medial border. cells uity of these nuclei in the rat. of different types appear. Some of these Along the lateral border of pars prin- cells are large and polygonal; others are cipalis the cells which constitute the pars small, round or spindle-shaped. and dark lateralis are more flattened and more staining in material showing Nissl gran- closely arranged than they are in the chief NORMAL AND ABNORMAL AUDITORY PATH 323 or central mass. The lateral portion is lium and, because of their absence, the very thin in the mouse and is not obscrved cortical areas are distinguished from one in the most caudal sections or in the ros- another chiefly on a cytoarchitectural tral fourth of the medial geniculate nu- basis. Both Drooglever Fortuyn ('14) and cleus. This part is the portion superficiezle Maxmillan Rose ('29) have given excellent of Ram6n y Cajal ('09). descriptions of the cytoarchitecture of the The third or ventral portion of pars mouse brain; the works of both authors principalis consists of spindle-shaped cells were used as references in the study of which are smaller and more ventrally lo- the animals reported here. cated than those of the other two parts The area ascribed to audition is sub- of the ventral group. The cells are ar- divided into two parts, the primary and ranged in a crescentic mass which is the secondary auditory areas, or TI and joined to the chief mass of pars principalis TS (Rose, '29). At the present time this caudally. This ventral portion corresponds subdivision in the mouse does not depend to area "c" of Winkler and Potter, and to upon functional but rests wholly upon noyau sus-pedunculaire of Ramdn y Cajal. histological differences. TI is bounded by In mouse brain no. 87120, it extends from the postcentral area anteriorly, the sec- 75 I-I anterior to the posterior pole of the ondary auditory area inferiorly, the oc- medial geniculate nucleus to the rostra1 cipital area posteriorly, and the parietal termination of this nucleus. It lies dorsal region superiorly. It extends farther cau- to the cerebral peduncle for most of its dalward than does the secondary auditory extent, and ventral to the main mass of area. Tz lies in relation to the postcentral pars principalis. Rostrally it is lateral to area anteriorly, the posterior insular area zona incerta at first, but then becomes and the ectorhinal area inferiorly, the OC- continuous with the latter medially and cipital area posteriorly, and the primary with the reticular nucleus anteriorly. Le auditory area superiorly. It extends far- Gros Clark ('30) has described a similar ther rostralward than does TI. termination for this group of cells in in- A six-layered plan of organization, with sectivores. modifications, exists in the mouse auditory In the mice studied, pars magnocellu- areas, as it does in all other neocortex. laris begins in the most caudal fifth of the According to the nomenclature used by medial geniculate nucleus. It ends ros- Brodmann ('09), these layers are, in lat- trally, along with pars principalis, by eromedial order: Layer I, lamina zonalis; merging with the cells of the ventral nu- Layer 11, lamina granularis externa; Layer cleus of the dorsal thalamus in sections 111, lamina pyramidalis; Layer IV, lamina through the anterior half of the posterior granularis interna; Layer V, lamina gan- commissure. Pars magnocellularis is com- glionaris; and Layer VI, lamina multi- posed of large, polygonal cells among formis. which are found small, spindle-shaped or In the primary auditory area (figs. 11, round cells. It has no subdivisions. Cau- 13), lamina zonalis is narrow and con- dally it lies medial to pars principalis tains very few cells; these cells are fusi- (fig. 9), but rostrally it is located dorso- form in type. The second layer is not medial to the latter portion of the medial distinct, but is masked by the medium- geniculate nucleus. sized pyramidal cells of the third layer. Auditory cortex. The three primitive Rose ('29), for example, spoke of Layer fissures found in all mammalian brains I1 + 111. The fourth layer is rather broad are present in the mouse. These are the and contains numerous granular cells hippocampal, the rhinal, and the endo- grouped together into clusters or knobs. rhinal fissures. The endorhinal fissure is These clusters are a characteristic feature not prominent macroscopically, but, under of the primary auditory area and serve to the microscope, the infolding of the cor- distinguish it from surrounding areas in tical laminae and the presence of the which such an arrangement of the gran- olfactory tract within the shallow groove ular cells of Layer IV is not found. Its thus created are evident. The mouse highly developed lamina granularis in- brain possesses no fissures in the neopal- terns suggests further that this area cor- 324 MURIEL D. ROSS responds to the auditory koniocortex of which possesses a broad Layer I and in higher forms. Layer V is of medium which Layers 11,111, and IV are indistinctly breadth and is divided into lateral, middle, separated from each other. and medial strata. The lateral and medial strata possess small pyramidal cells that Re'sumS of acoustic pathways are widely scattered; however, rather in normal mice closely arranged large pyramidal cells are The first neurons in the acoustic path- found in the middle stratum. The sixth way are bipolar cells, the cell bodies of layer consists of polymorphous cells which which are located in the spiral ganglia are more densely arranged directly be- within the cochlea. The dendrites of these neath the fifth layer than they are in the cells extend peripheralward to terminate deeper part of the layer. on the hair cells of the organ of Corti. The primary auditory area differs from Their axons accumulate on leaving the surrounding areas chiefly in the character- spiral ganglia to form the cochlear division istic arrangement of the internal granular of the eighth cranial nerve. The cochlear layer (figs. 11, 13). It may be distin- division comes into relation with the vesti- guished also from the parietal area by the bular part of the acoustic nerve on its larger size of the pyramidal cells found course centralward, but enters the medulla in Layer V of the latter area; from the oblongata posterior to the latter and ven- postcentral area with its broader Layers tromedial to the ventral cochlear nucleus. I11 and V; from the occipital area where Each fiber of the cochlear nerve divides a broader Layer I, narrower Layer IV, and immediately into a ventral and a dorsal lack of stratification in Layer V are ob- descending branch (v. Kolliker, 1896; served; and from the secondary auditory Held, 1893; RamBn y Cajal, '09; and area in which both Layers I and V are others). The destination of the ventral broader. ascending branch is the ventral cochlear The secondary auditory area possesses a nucleus, and the dorsal, descending branch Layer I of about medium breadth. Layer terminates in the acoustic tubercle and in I1 is again masked by the medium-sized the dorsal extension of the ventral cochlear pyramidal cells of Layer 111. The fourth nucleus. layer exhibits no clustering of its granular The axons of the secondary acoustic cells. Layer V is very broad and is divided neurons on leaving the dorsal and the into lateral, middle, and medial strata. ventral cochlear nuclei ascend by several The middle stratum is broad and is com- routes to higher centers. A bundle of fibers posed of large pyramidal cells; the lateral emerges dorsomedially from the fourth and middle strata possess small pyramidal layer of the acoustic tubercle as the sec- cells. The sixth layer is narrower than in ondary dorsal cochlear fibers. These fibers the primary auditory area and its poly- swing dorsalward over the restiform body, morphous cells are more closely grouped then medialward through the region of in its more superficial portion. the vestibular nuclei, becoming separated The secondary auditory area is distin- into smaller fascicles during their course. guished from the postcentral, the occipital, Many of the fibers cross the midline in the and the primary auditory areas by its region ventral to the medial longitudinal rather broader Layer I and its very wide iasciculus, forming the dorsal acoustic Layer V. It differs from the postcentral decussation, before turning ventralward area also in possessing a narrower Layer to reach the region dorsolateral to the IV than does the latter. The secondary superior olive. Here they join secondary auditory area is easily distinguished from acoustic fibers from the ventral cochlear the areas located ventral (or inferior) to nucleus to form the lateral lemniscus. it. Inferior to it, anteriorly, lies the pos- The number of secondary dorsal cochlear terior insular area in which a very wide fibers remaining on the same side could Layer I and narrow Layers I1 and I11 are not be determined in these mice. found, and in which Layer IV is not evi- From the ventral cochlear nucleus, sec- dent. Inferior to the secondary auditory ondary acoustic fibers course ventromedial- area, posteriorly, lies the ectorhinal area ward as the fibers of the trapezoid body. NORMAL AND ABNORMAL AUDITORY PATH 325

These fibers pass below or around the late nucleus directly through the lateral superior olive, through the region of the lemniscus, or indirectly, after synapsing in medial lemniscus, cross the midline in the the nucleus of the inferior colliculus. ventral acoustic or trapezoid decussation, The geniculocortical fibers gather me- and enter the contralateral lateral lem- dial to the anterior part of the medial niscus. The trapezoid decussation is much geniculate nucleus. They assume a more heavier than the dorsal decussation in the lateral position as all of the cells of pars mouse. The more dorsal fibers of the principalis except those situated most ven- trapezoid body are spread apart lateral to tromedially disappear near the rostral tip the medial lemnisci by the nuclei of the of the nucleus. These fibers form the audi- corpus trapezoideus. Numerous fibers ramify within these nuclei. In higher forms tory radiations which run to the cerebral it is generally conceded that some of the cortex along with the dorsal thalamic ra- secondary neurons from the ventral coch- diation. The course of the auditory radi- lear nucleus synapse in the trapezoid and ations in the mouse corresponds to that olivary nuclei, and that contributions from previously described in the rat by Gurd- these nuclei join the lateral lemnisci to jian (’27) and in many other mammals ascend to higher auditory centers. by various observers. There are thought Between the dorsal and the ventral to be corticocollicular as well as afferent acoustic decussations is the decussation fibers with respect to the auditory cortex of Held. The fibers crossing the midline in the auditory radiations. here appear, in the available material, to DESCRIPTION OF MATERIAL originate in the dorsal portion of the ven- FROM DEAF MICE tral cochlear nucleus as described by Ram6n y Cajal (’09) and Yoshida (’24). Primary auditonj centers These fibers run dorsalward over the resti- Dorsal cochlear nucleus. The acoustic form body and then dip ventralward im- tubercle begins caudally at the level of the mediately to gain a position between the lateral recesses of the fourth ventricle. It dorsal secondary acoustic fibers and the diminishes to a narrow band of cells over trapezoid body. The fibers of Held are not the dorsal surface of the ventral cochlear numerous in the mouse. nucleus in the plane of the facial roots; The lateral lemniscus is composed, then, these cells are present to the rostral termi- of secondary cochlear fibers from the ven- nation of the ventral cochlear nucleus. tral cochlear nucleus of the opposite side The caudorostral extent of the acoustic and from the acoustic tubercle of the same tubercle in the deafened animals corre- and of the opposite side. It also carries sponds, then, to that in the normal mice. fibers from the trapezoid and olivary nu- The dorsal cochlear nucleus is not dimin- clei. In this manner, both ears are repre- ished in length or in breadth in the deaf sented in each lateral lemniscus. mice, but is considerably flattened at all At lower midbrain levels the lateral levels (figs. 4, 5, 6). Along with the flat- lemniscus swings dorsolateralward (fig. 7). tening of the nucleus there is a loss of Both superior and inferior nuclei of the internal organization of the nucleus which lateral lemniscus are present and probably is more complete on the right side of both receive collaterals from, and add fibers to, specimens, but which is more extensive in the lateral lemniscus. In the mouse, many mouse no. 85836 than in mouse no. 85842. of the fibers of the lateral lemniscus enter The medium-sized ovoid cells and the the inferior colliculus. Fibers leave the smaller spindle-shaped cells conspicuous inferior colliculus laterally, turning ven- in the posterior part of the acoustic tuber- tralward in the capsular region. They join cle in the normal mouse brain are not the portion of the lateral lemniscus which present in mouse no. 85836. Instead, nu- does not enter the collicular gray; together merous small, darkly-staining, round nu- these fascicles constitute the peduncle of clei of cells which resemble “grains” or the inferior colliculus, which enters the “granules” are prominent in this nucleus medial geniculate nucleus caudomedially. as well as in all of the higher centers for Thus, fibers project to the medial genicu- hearing in this abnormal brain. The pres- 326 MURIEL D. ROSS ence of many of these granule-type cells, mouse no. 85836. It is divisible into an- then, is a characteristic feature of the terior and posterior parts as in the normal changes occurring in the auditory centers animal. of the old, deaf, epileptic waltzing mice. The cells of the ventral cochlear nucleus Similar cells may be demonstrated in the are closely grouped and usually pale-stain- normal mouse brain, but they are more ing in cell material, although occasionally scattered and appear to be less numerous they assume a characteristic violet color than in the abnormal material. Where in Nissl preparations. They are ovoid or they occur, these cells will be referred to round rather than triangular in shape and as “granule-type” cells in the rest of the the central parts of the cell processes are description given here. They may be phag- ghost-like. At the level of the vestibular ocytic microglia which have invaded the division of the acoustic nerve, some of the various auditory nuclei; but, since special cells in the medial portion of the ventral staining techniques for demonstrating neu- cochlear nucleus are triangular-shaped roglia were not used, this cannot be stated and have well-stained Nissl granules. with certainty. These cells are closely grouped, however, In sections at the level of the facial and numerous granule-type cells are scat- nucleus in this deaf mouse there is an tered between them. They can be traced indication of lamination of the tubercle. for only 30 p. The superficial layer is composed of few At no level does the ventral cochlear cells, as is the case normally. The typical nucleus assume the shape or attain the fusiform cells of the second layer, lamina size typical of the normal mouse brain. cellularis, are not observed here or at any The most caudal part of the nucleus is other le~lin the nucleus; instead, the much more nearly flat and narrower than cells are large, ovoid, and pale-staining. in the normal material (fig. 5). It is ex- This layer is differentiated from the other tremely difficult to locate the cochlear laminae because its numerous granule- nerve fibers in mouse brain no. 85836. At type cells give it a very dark appearance. the level of the entrance of the vestibular Layers I11 and IV in mouse no. 85836 nerve the ventral cochlear nucleus has a consist of large, pale-staining cells, also, triangular shape; the base of the triangle and there is a proliferation of granule-type is medialward and its apex points lateral- cells especially medially. Thus, these ward (fig. 6). The dorsal side of the tri- layers cannot be distinguished from one angle is concave; the ventral side is another. The region of nucleus proprius straight at first, but within 100 LI also is filled with the small granule-type cells. shows a concave curvature and becomes There are no fibers in the caudal fourth very short. The rostral one-half of the of the acoustic tubercle or at any level in ventral chochlear nucleus consists of a nucleus proprius in mouse brain no. 85842. flat layer of closely arranged cells; its Delicate fibrils appear in the ventromedial dorsolateral surface is long and concave. part of the acoustic tubercle in the second The nucleus diminishes in size very grad- fourth ol its extent and gradually become ually to its rostral termination. Far an- more numerous. The fibers are most nu- teriorly the granule-type cells are numer- merous in the anterior half of the nucleus ous ventrally and along the dorsal surface and here, also, lamination becomes evi- of the nucleus. dent. The layers are thin and the fibrils In mouse brain no. 85842 the ventral in the second and third laminae are few cochlear nucleus also exhibits its greatest in number and very dose to one another. size in sections immediately anterior to Layer IV is composed of small fascicles the level of the cochlear nerve. It differs which are entering the acoustic tubercle from this nucleus in mouse no. 85836 in ventrally, and of others which are leaving that it is more rounded and not nearly so the nucleus dorsally. triangular in shape at these levels (fig. 4). Ventral cochlear nucleus. The ventral Caudally, there are no fibers in the ventral cochlear nucIeus extends from the level part of the nucleus. Cochlear nerve fibers, of the facial nucleus caudally to that of very few in number, enter the medulla the motor trigeminal nucleus rostrally in oblongata lateral to the spinal tract of V NORMAL AND ABNORMAL AUDITORY PATH 327 and divide into ascending and descend- Nuclei of the lateral lemniscus. The ing branches. Some of the descending inferior nucleus of the lateral lemniscus branches cross the ventral cochlear nu- is composed of closely arranged, polygonal cleus, dividing it into several laminae, or fusiform cells of medium-size. Here, to enter the dorsal extension of the nu- again, granule-type cells appear to be more cleus. The ascending branches are most numerous than in the normal material. numerous in the ventrorostral part of the Anteriorly, the inferior nucleus is con- nucleus. The ventral cochlear nucleus, nected to the superior nucleus of the lat- except in sections at, and immediately in eral lemniscus by strands of cells which are part of the latter nucleus (fig. 8). front of, the entrance of the cochlear These strands are widely separated in nerve, is extremely flat. mouse brain no. 85836, indicating the Nuclear complex of the superior olive. passage of many fibers; in mouse no. The cells of the superior olive in mouse 85842 there are marked fiber connections brain no. 85836 are of medium-size and between these nuclei. are polygonal or fusiform in shape. They The dorsal portion of the superior nu- are very close together and granule-type cleus of the lateral lemniscus consists of cells are numerous among them (fig. 5). fusiEorm cells which are arranged with The cells appear to follow the curves or their long axes in a horizontal plane. The foldings of the nucleus, but aside from this cells are closer to one another than they arrangement no folding, such as charac- are in normal material. In mouse no. terizes the normal superior olive, could be 85842, very few fibers enter the nucleus demonstrated. The superior olivary nu- of the inferior colliculus from the superior cleus is atrophied at all levels in mouse nucleus of the lateral lemniscus. brain no. 85836. In mouse no. 85842 it is Inferior colliculus. The inferior colic- smaller than normal but appears as a ulus is divided into a central nucleus and folded mass of gray which contains fibers a peripheral capsular portion, as is the throughout its entire extent (fig. 4). case in the normal animal. The central The accessory superior olive also con- nucleus is a dense, cellular area; the large sists of medium-sized fusiform or poly- polygonal cells characteristic of this nu- gonal cells which are closely grouped cleus are present, but between them and together. There is an increase in the in the capsular portion are numerous gran- number of granule-type cells in this nu- ule-type cells. The dark, round nuclei of cleus in mouse no. 85836. In both speci- these cells are conspicuous and give a mens the accessory superior olive is more granular appearance to the inferior col- typical in size anteriorly than posteriorly. liculi (fig. 8). In mouse no. 85842 there The parolivary nuclei are difficult to are many fine fibers in the central nucleus, demonstrate in these preparations. There but few fibers enter the peduncle of the is a little gray between the fibers of the inferior colliculus. trapezoid body ventral and ventrolateral Medial geniculate nucleus. The medial to the superior olive in mouse brain no. geniculate nucleus begins caudally at the 85842. In mouse no. 85836 a few poly- level of the superior colliculus and termi- gonal cells are found in these nuclei. nates rostrally in sections through the mid- The nuclei of the trapezoid body are dle third of the posterior commissure. well developed in both mice. The cells of Anteriorly, the cells of this nucleus are the trapezoid gray are of medium-size and confluent with the cells of the ventral polygonal or ovoid in shape. They are nucleus of the thalamus. In these respects, closely arranged in mouse no. 85836 and then, the deaf mice do not differ from the there is a proliferation of granule-type normal animals. They do differ from them cells in the nucleus. In mouse no. 85842, in that the medial geniculate nucleus is although there are fewer fascicles separat- atrophied in the deaf mice, especially lat- ing the gray of the nucleus, many fibers eromedially and dorsally, and there is a leave it medially, and there is a heavy lack of the typical internal organization. trapezoid decussation in the region be- Most caudally the medial geniculate nu- tween the gray of the two sides. cleus of mouse brain no. 85836 is a small 328 MURIEL D. ROSS mass of compactly arranged cells. Some Auditory cortex. The histological struc- of these cells are ovoid, medium-sized ture of the auditory cortex is not well neurons; others are granule-type cells. As differentiated in mouse brain no. 85836 the nucleus increases in size, pars prin- except in a few areas. The most prom- cipalis and pars magnocellularis are dis- inent feature of the degeneration in the tinguish able. auditory cortex of this animal is the sim- Pars principalis is laterally situated and ilarity of the cells in Layers 11, 111, and IV; is composed of pale, ovoid cells of medium- these cells are ovoid in shape and size, and of many prominent granule-type possess pale-staining nuclei and cytoplasm cells (fig. 10). The nuclear membranes (fig. 12). The proportion of granule-type of the ovoid cells are well-stained and cells appears to be increased in the audi- clearly visible, but neither the cytoplasm tory areas of the deaf mice, but these nor the karyoplasm stain well. Frequently cells are not nearly so conspicuous here the cell processes are pale or do not stain as they are in the primary acoustic nuclei. at all. The dark, triangular or spindle- Layer I of the primary auditory area in shaped cells of the dorsal group are not mouse brain no. 85836 is relatively un- present; granule-type and ovoid cells are affected. Layers I1 and 111 are confluent found in this part of pars principalis. Lat- and consist of the inflated, ovoid cells erally, the cells are ovoid, also, and are described above. There are a very few much more closely arranged than in the dark, small pyramidal cells in the medial normal material. The central mass of part of Layer I11 on the right side. These pars principalis is atrophied in its entire are located in the most superior and ros- caudorostral extent. The ventral part of tral portion of the primary auditory area this nuclear mass, which is less atrophied and are not observed elsewhere. There is than the more dorsal portion, contains a clustering of the granular cells in Layer some scattered triangular or fusiform cells. IV superiorly in the rostral third of the The most ventral cell group of pars prin- auditory koniocortex; this clustering is bi- cipalis is filled with granule-type cells, lateral. Immediately ventral to the clus- although a few pale, ovoid cells can be ters, Layer IV thins out and the cells are distinguished. not arranged in knobs, as in typical audi- Pars magnocellularis of the medial gen- tory cortex. Layers I1 + I11 and IV are iculate nucleus is poorly defined caudally. confluent here as well as in the entire Its cells are close to one another and caudal two-thirds of the primary auditory numerous granule-type cells are present area. Layer V is also best differentiated here as well as in the area between this rostrally. Its three strata are distinct, d- nucleus and pars principalis. In its rostral though the large pyramidal cells of the third the large, polygonal cells typical of middle stratum are slightly enlarged and this area in the normal mouse brain are take a pale stain. This stratification is not occasionally evident. observed caudally. Layer VI is composed The degeneration is very similar in the of polymorphous cells which do not appear medial geniculate nuclei of mouse brain to differ in arrangement at different no. 85842 and mouse brain no. 85836. depths. The caudal fourth of pars principalis in Layer I of the secondary auditory area mouse brain no. 85842 is devoid of fibers is not affected in this mouse brain. Layers exccpt most ventrally. Fibers are present 11, 111, and IV are indistinct, all of them in the anterior three-fourths of this nu- being composed of pale, ovoid cells. cleus and, in this better preserved portion, Layer V is very broad, and its pyramidal they are most numerous centrally. A few cells are large and “ghost-like.” Layer VI fibers ramify laterally and dorsally in pars is not differentiated into superficial and principalis at the level of the caudal pole deep strata. On the left side Layers 11, of the dorsal part of the lateral geniculate 111, IV and V are confluent, indicating nucleus. Rostra1 to this level, pars prin- that degeneration is more complete, and cipalis is an oval-shaped gray mass in perhaps has occurred earlier on this side. which there are few fibers. The small Unfortunately, a few of the sections of pars magnocellularis is never rich in fibers. the auditory cortex are missing from the NORMAL AND ABNORMAL AUDITORY PATH 329 left side in mouse no. 85842; these were tral cochlear nucleus is smaller than nor- lost in preparation of the material. In the mal and triangular in shape. rest of the sections fibers reach the audi- A few fascicles swing dorsalward from tory areas and, in some cases, radiate into the acoustic tubercles of mouse no. 85842; Layer IV. The primary auditory area ex- they turn ventromedialward to cross the hibits a knob-like arrangement of Layer midline in the dorsal acoustic decussation. IV rostrally on both sides. This is best There are also a few fibers of Held which seen superiorly on the right and inferiorly arise in the dorsal extension of the ven- on the left. There are clusters of neurons tral cochlear nucleus in this material, run in the fourth layer throughout approxi- dorsalward over the restiform body, and mately the caudal third of the right konio- then dip ventralward (fig. 4). It is im- cortex. Delicate fibers can be traced possible to determine the percentage of through Layer IV in this region. secondary dorsal acoustic fibers remaining The secondary auditory area is better on the same side. The secondary acoustic supplied with fibers on the right side than neurons from the acoustic tubercle and on the left. The fibers enter Layer I1 + the dorsal extension of the ventral coch- 111 toward the middle of the area. On the lear nucleus enter the lateral lemniscus, Left side fibers are found only in Layer VI lateral to the superior olive, where they and in the medial part of Layer V. are joined by other fibers from the contralateral ventral cochlear nucleus. The fas- Acoustic pathway in deaf mice cicles from the ventral cochlear nucleus None of the parts of the acoustic path- are not so numerous as in the normal way are completely degenerated in these brain. They leave the nucleus ventrome- deaf mice, except the roots of the cochlear dially and may send collaterals into the nerve on both sides in mouse brain no. nuclear complex of the superior olive and 85836. The fibers in other portions of the into the trapezoid gray. In spite of the auditory pathway are greatly diminished fact that fewer fibers of‘ secondary neu- in number. rons leave the ventral cochlear nuclei in The cochlear nerve is much reduced in both abnormal brains, there is a well de- size even in mouse no. 85842. It appears veloped trapezoid body medial to the trape- to be about one-third the size of the nerve zoid gray, and a heavy ventral acoustic in the normal mouse. Upon entering the decussation. medulla oblongata, each fiber bifurcates R~SUM~ into two branches : the descending branch runs in a dorsal direction through or me- In general then, a high degree of or- dial to the ventral cochlear nucleus to end ganization is not to be found in the acous- in the dorsal extension of this nucleus and tic centers in the deaf mice. Instead, in the acoustic tubercle; the ascending there is usually a lack of organization; branch terminates in the ventral cochlear the cells of the various nuclei are fre- nucleus. This bifurcation of the acoustic quently inflated and “ghost-like’’ in ap- nerve is well defined in sections cut at an pearance, and the laminae of the acoustic angle. Within the primary acoustic nuclei tubercles and of the auditory cortex are the regions containing most fibers are usually confluent. The fibers, when pres- those close to the entrance of the cochlear ent, are delicate. The most striking change nerve. The acoustic tubercles are almost is in the appearance of the ventral coch- completely degenerated in mouse no. lear nuclei, for in the deaf mice they are 85836, but only the caudal fourth of these atrophied and they may have a triangular nuclei entirely lack fibers in mouse no. shape. Normally, these nuclei have a 85842. Nucleus proprius in the latter plump, rounded contour. mouse brain is atypical throughout its ex- There is no doubt that the older, epilep- tent. The ventral cochlear nucleus is larg- tic waltzers become deaf due to degenera- est and best supplied with fibers at the tive changes within the auditory centers level of. and iust anterior to, the entrance and pathway. The interesting aspect of of the cochlear nerve (fig. 4). At similar this degeneration is that the entire svstem levels in mouse brain no. 85836 the ven- is involved, rather than one particular 330 MURIEL D. ROSS portion of it. There is some evidence that Held, H. 1893 Die centrale Gehorleitung. Arch. the degeneration affects particularly the f. Anat. u. Entwickl. (Leipzig), pp. 201-248. Kolliker, Von A. 1896 Handbuch der Gewebe- primary acoustic nuclei, however, for these lehre des Menschen. Bd. 2. W. Engelinann, nuclei are almost completely atrophied in Leipzig, 874 pp. the deaf mice, while a few typical appear- Le Gros Clark, W. 1930 The thalamus of Tar- ing cells and cell groupings are observed sius. J. Anat. (Lond.), 64: 371-414. 1933 The medial geniculate body and at higher levels. Although the right pri- the ganglion isthmi. Ibid., 67: 536-548. mary acoustic nuclei are more atrophied Lorente de N6, R. 1933 Anatomy of the eighth than the left, the higher centers are more nerve. 111. General plan of structure of the primary cochlear nuclei. Laryngoscope, 43: severely affected on the left side. All of 327-350. these factors indicate either a gradual, Malone, E. F. 1910 Ueber die Kerne des simultaneous degeneration of the various menschlichen Dienceuhalon. Abhandl. d. kon. auditory centers corresponding with the preuss. Akad. d. Wiss&h., Berlin, Phys.-math. gradual loss hearing exhibited by the C1. Abh 1, 32 pp. of Ram6n y Cajal, S. 1909 Histologie du systhme animals, or else a transneuronal type of nerveux de l’homme et des -vert&ds. A. degeneration. Maloine, Paris, Vol. I, 986 pp. In order to determine more exactly the 1911 Histologie du systeme nerveux de l’homme et des vertebres. A. Maloine, Paris, nature and course of the degeneration, it voi. Ir, 993 pp. is necessary to examine the auditory path- Rioch, D. McK. 1929 Studies on the diencepha- ways of partially deaf epileptic waltzers. lon of Carnivora. Part I. The nuclear config- This will be done in Part I1 of this study. uration of the thalamus, eipthalamus, and hy- pothalamus of the dog and cat. J. Comp. Neur., LITERATURE CITED 49: 1-119. Rose, M. 1929 Cytoarchitektonischer Atlas der Brodmann, K. 1909 Vergleichende Lokalisa- Grosshirnrinde der Maus. J. f. Psychol. u. tionslehre der Grosshirnrinde in ihren Prin- Neurol., 40: 1-51. zipien dargestellt auf Grund des Zellenbaues. Vogt, C. 1909 La mydoarchitecture du thala- J. A. Earth, Leipzig, 334 pp. mus du cercopithhque. Ibid., 12: 285-324. Crosby, E. C., and J. W. Henderson 1948 The Walker, A. E. 1937 The projection of the me- mammalian midbrain and isthmus regions. dial geniculate body to the cerebral cortex in 11. Fiber connections of the superior colliculus. the macaque monkey. J. Anat. (Lond.), 71: B. Pathways concerned in automatic e+e move- 315-344. ments. J. Comp. Neur., 88: 53-92. 1938 The primate thalamus. The Univ. Dice, L. R. 1935 Inheritance of waltzing and of Chicago Press, Chicago, 321 pp. of epilepsy in mice of the genus Peromyscus. Watson, M. L. 1939 The inheritance of cpi- J. Mammalogy, 16: 25-35. lepsy and of waltzing in PCTOVZ~SCUS.Disserta- Fortuyn, A. B. Droogleever 1914 Cortical cell tion. Contributions from Lab. of Vert. Gen., lamination of the hemispheres of some rodents. 11: 1-24. Arch. Neurol. Psychiat., 6: 221-354. Winkler, C., and A. Potter 1911 An anatomical Guild, S. R. 1919 War deafness and its pre- guide to experimental researches on the rabbit’s vention - report of the labyrinths of the ani- brain. W. Versluys, Amsterdam, 40 frontal mals used in testing of preventive measures. sections. (Middle ears previously reported ) . J. Lab. & 1914 An anatomical guide to experi- C1. Med., 4: 1-28. mental researches on the cat’s brain. W. Ver- Gurdjian, E. S. 1927 The diencephalon of the sluys, Amsterdam, 35 frontal sections. albino rat. Studies on the brain of the rat. No. Yoshida, I. 1924 Ein Beitrag zur Anatomie des 2, J. Comp. Neur., 43: 1-114. Octavus. Folia anat. japon., 2; 275-281. PLATES

Abbreviations to plates Ac. tub., Acoustic tubercle Nuc. prop., Nucleus proprius “chief mass,’’ “chief mass” of pars principalis of Outer str., Outer stratum of Lamina V of the the medial geniculate nucleus primary auditory cortex Coch. N., Cochlear Nerve P. magnoc., Pars magnocellularis of the medial d. gr., Dorsal group of pars principalis of the geniculate nucleus medial geniculate nucleus P. pin., Pars principalis of the medial geniculate Fib. from “tail” post. subd. v. coch. nuc., Fibers nucleus from the “tail” of the posterior subdivision Post. subd. v. coch. nuc., Posterior subdivision of of the ventral cochlear nucleus the ventral cochlear nucleus Inner str., Inner stratum of Layer V of the pri- Rest. body, Restiform body mary auditory cortex Rost. subd. v. coch. nuc., Rostra1 subdivision of 1. gr., Lateral group of pars principalis of the the ventral cochlear nucleus medial geniculate nucleus Sp. tr. V, Spinal tract of V L. lem., Lateral lemniscus Sup. nuc. 1. lem., Superior nucleus of the lateral L. zone, Lateral zone of the ventral cochlear nu- lemniscus cleus Sup. 01. nuc., Superior olivary nucleus L. I to L IV, Layers of the acoustic tubcrcle “Tail” post. subd. v. coch. nuc., “Tail“ of the Lam. I to VI, Laminae of the primary auditory posterior subdivision of the ventral cochlear cortex nucleus M. zone, Medial zone of the ventral cochlear Trap. body, Trapezoid body nucleus v. gr., Ventral group of pars principalis of the Med. gen., Medial geniculate nuclcus medial geniculate nucleus Middle str., Middle stratum of Lamina V of the V. coch. nuc., Ventral cochlear nucleus primary auditory cortex V. port. post. subd. v. coch. nuc., Ventral portion Nuc. inf. col., Nucleus of the inferior colliculus of the posterior subdivision of the ventral Nuc. inf. 1. lem., Inferior nucleus of the lateral cochlear nucleus lemniscus PLATE 1

EXPLANATION OF FIGURES

1 A transverse section through the caudal part of the acoustic tubercle of mouse brain no. 87120 to show the beginning of lamination within the tubercle. Cresyl-echt-violet stained preparation. X 60. 2 Normal mouse brain no. 87120. The acoustic tubercle and the posterior subdivision of the ventral cochlear nucleus are shown in this transverse section. Cresyl-echt-violet stained preparation. x 50. 3 The acoustic tubercle and the anterior subdivision of the ventral cochlear nucleus of the normal mouse are shown in a cross section at a level through the caudal part of the genu of VII. This photomicrograph shows the rounded contour of the ventral cochlear nucleus as the “tail” of the posterior subdivision of this nucleus dis- appears. Mouse brain no. 87120. Cresyl-echt-violet stained preparation. X 50.

332 NORMAL AND ABNORMAL AUDITORY PATH PLATE 1 Muriel D. Ross

FIG. 2. FIG. 3.

333 PLATE 2

EXPLANATION OF FIGURES

4 This transverse section through the dorsal and ventral cochlear nuclei of the deaf mouse, (brain no. 85842), at the level of the cochlear nerve shows a few fibers from the “tail” portion passing dorsalward. Note the general loss of fibers exhibited throughout the section. Weil stained preparation. X 25. 5 Note the close arrangement of the small, dark-staining nuclei of the granule-type cells in the abnormal dorsal and ventral cochlear nuclei in this transverse section. The pronounced lack of organization within the superior olivary nucleus also may be observed. Mouse brain no. 85836 (deaf). Cresyl-echt-violet stained preparation. X 25. 6 A transverse section through the anterior subdivision of the ventral cochlear nucleus at the level of the cochlear nerve is shown here. This section is from the deaf mouse no. 85836 series, and may be compared with figures 3 and 4 to show the profound changes in internal organization and in contour which have occurred in the ventral cochlear nucleus of this brain. Cresyl-echt-violet stained preparation. x 45.

334 NORMAL AND ABNORMAL AUDITORY PATH PLATE 2 Muriel D. Ross

FIG. 4.

FI GI 5. FIG. 6. PLATE 3

EXPLANATION OF FIGURES

7 A transverse section at the level of the inferior colliculus in the normal mouse, no. 87932, Weil stained preparation. X 32. 8 A transverse section at the level of the inferior colliculus in the deaf mouse, no. 85836. The granule-type of cell is very conspicuous throughout the level and a diminution in breadth of the brain is obvious. Cresylecht-violet stained preparation. X 20. 9 The various groups of pars principalis in the normal medial geniculate nucleus are shown here. The dorsal group is especially clear. Mouse brain no. 87120. Cresyl-echt-violet stained preparation. X 32. 10 This is a photomicrograph of a transverse section through the medial gcniculate nucleus of the deaf mouse (no. 85836) at the same level as the section shown in figure 9. The cells of the various groups of pars principalis resemblc each other closely. Typically they are swollen and pale staining, so that the groups can not be differenti- atcd. Cresyl-echt-violet stained preparation. x 50.

336 NORMAL AND ABNORMAL AUDITORY PATH PLATE 3 Muriel D. Ross

FIG, 8. FIG. '2 Nuc.inf. I. lem,

FIG. 9, FIG. 10.

337 PLATE 4

EXPLANATION OF FIGURES

11 The primary auditory cortex of the normal mouse brain may be divided into six layers as is shown in this photomicrograph. This section was taken from the middle third of the extent of the primary auditory area of mouse brain no. 87932. The clusters or “knobs” in Lamina IV are especially obvious in the Weil preparation. Weil stained preparation. x 65. 12 This section shows the inflated-appearing, “ghost-like” cells which appear in Laminae 11, 111, IV, and V of the primary auditory cortex in the deaf mouse (brain no. 85836). The changes in size and shape of the cells as well as the loss of internal organization of the cortex may be quickly demonstrated by comparing this section with a similar level in the normal mouse brain as is given in figure 13. Cresyl- echt-violet stained preparation. x 65. 13 A transverse section through the middle third of the auditory cortex of the normal mouse (no. 87120). The clustering of Lamina IV is evident as is the layering of the fifth Lamina. The cells of Lamina VI are divided into numerous bands or “sheets” by the fibers which course between them. Cresyl-echt-violet staincd preparation. x 55.

338 NORMAL AND ABNORMAL AUDITORY PATH PLATE 4 Muriel D. Ross

FIG. 11.

FIG. 12. FIG. l3*

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