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Eye muscle motor neurons with different functional characteristics
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SHORT COMMUNICATIONS
Eye muscle motor neurons with different functional characteristics There are differences in the size of eye muscle motoneuronsg, 2z and in the diamete# and conduction velocity of their axonsZ, 26. There are also diverse types of eye muscle fibers ranging from fast singly-innervated twitch fibers to slow multi-innervated fibers with graced contractionsZ,~,10,14-16, 22. Therefore, recent reportsT,S,12, 21 that all oculomotor, abducens, and trochlear motoneurons have similar activity patterns are somewhat surprising. In this paper we report attempts to determine whether this was correct by studying the qualitative characteristics of motoneurons of monkeys during spontaneous saccades and positions of fixation. Unit activity was recorded in the oculomotor and abducens nuclei and nerves of alert restrained monkeys (Macaca mulatta) with tungsten microelectrodes of 2-10 M f L The monkeys looked about spontaneously and moved their eyes in all directions. Deviations were generally within 4- 20 ° of the midposition with horizontal eye movements predominating. Whenever units were held long enough, objects were introduced into the peripheral fields to induce larger gaze shifts. Electrodes were inserted into the brain through an implanted plug in a 0.8 mm guide tube, and were advanced with a hydraulic microdrive (Trent Wells, Southgate, Calif.). Stable recordings of action potentials between 100 #V and 5 mV over periods of 20 sec to 100 min were analyzed. In one animal a bipolar stainless steel electrode for antidromic stimulation was implanted in the IIIrd nerve using stereotaxic techniques. Horizontal and vertical eye movements and positions of fixation were recorded with platinum needle electrodes using DC-coupled amplifiers. The electrooculogram (EOG) was calibrated using horizontal and vertical optokinetic and rotatory stimuli of known velocitieslA3. Eye movements and unit data were stored on FM magnetic tape and displayed on a storage oscilloscope. The frequency of unit activity was determined by a small, general purpose digital computer or by a frequency meter. The latter gave a pulse at the time of each spike whose voltage was proportional to the reciprocal of the preceding interspike interval. Electrolytic lesions were later, made above and below recording sites to identify electrode tracks in histological sections. Identification of motoneurons and general characteristics. Recordings were taken from 32 units in the oculomotor nerve. An electrode track through the oculomotor nerve (IIIrd nerve) rootlets is shown in Fig. 1A. Units in the nerve which changed their activity before the onset of eye movements were considered to be axons of motoneurons. Activity of 138 units was also recorded in the oculomotor and abducens nuclei. The trochlear nucleus was not explored. Unit activity in the nerve differed in a number of respects from activity in the motor nuclei: action potentials in the nerve had no inflection on the rising phase; no cells or fibers were found which were loosely coupled to eye movement or which changed activity during eye movement in all directions; and units associated with eye movements in different directions and with blinks were packed closely together without the spatial separation found in the oculomotor nucleus. An electrode track through the oculomotor nucleus is shown in Fig. lB. The site of recording was about 5.5 mm distant to that in Fig. 1A. Eighty-nine of the 138
Brain Research,45 (1972) 561-568
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Fig. 1. A, B, Electrode tracks through the rootlets of the oculomotor nerve (A, I11 R, arrow) and oculomotor nucleus (B, III Nuc). In A lesions (L) were later made above and below the recording site at the time of killing. The dentato-thalamic fibers (dt) and habenulo-interpedunctdar tract (thi) are also labelled. The section in A is in the A ÷ 8 vertical stereotaxic plane and in B is in the A I 3 plane. The two recording locations are separated by 5.5 ram. Weil and cresyl violet stains.
units encountered in the m o t o r nuclei were believed to be motoneurons. Several were identified by antidromic stimulation. The rest were presumptively identified because o f the site o f recording and because their activity patterns were the same as units in the m o t o r nerve. These included units associated with abduction (lateral rectus units), adduction (medial rectus units), and depression and adduction (inferior rectus units). Superior rectus and inferior oblique m o t o n e u r o n s are not readily separated on the basis o f site o f recording and direction o f eye movement, since cells responsible for m o v e m e n t o f both eyes up and to the same side are located in adjacent parts o f one o c u l o m o t o r nucleus 2a. Consequently, they were grouped together. The approximate locations o f units associated with different muscles in the m o t o r nuclei corresponded to the description o f Warwick 25. Forty-nine o f 138 units from the I I I r d and VIth nerve nuclei had activity patterns which were different f r o m motoneurons. These were considered to be prem o t o r or central units. Some were ' m i r r o r units'. They had most o f the characteristics o f motoneurons, but their o n - o f f direction was just the reverse o f adjacent m o t o r units. These included units in the abducens nucleus which were associated with adduction, or in the o c u l o m o t o r nucleus associated with abduction. They may correspond to interneurons described in the eye muscle m o t o r nuclei of cat 11,17. M o t o r units generally had increases or decreases in firing frequencies 5-8 msec before the onset o f eye movement. F o r units with transient increases in activity during eye movements (see below), the firing rates decreased about 5-8 msec before the movement ended 7,s,18. The reverse was true during transient decreases in activity. M o s t units had some change in activity during eye movements in almost every direction, but there was a preferred plane o f movement, the o n - o f f direction, in which changes in Brain Research, 45 (1972) 561-568
SHORT COMMUNICATIONS
563
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Fig. 2. Top trace, unit recording; middle trace, horizontal EOG; bottom trace, vertical EOG. Eye movement to the right and up caused upward deflection of the 2nd and 3rd traces, respectively, in this and in Fig. 3. Basis for identification of motoneurons is given in text. A, Tonic inferior rectus motoneuron. B, Phasic medial rectus motoneuron. C, D, Predominantly tonic medial rectus motoneuron. Inhibition during the movement in the off-direction in D was accomplished over one or several interspike intervals, and the unit was not completely inhibited except when firing near threshold. E, F, Large unit was a predominantly phasic inferior rectus motoneuron which fired with a burst of spikes during downward eye movements over wide ranges of deviation. Only when the eye was strongly depressed (F) did tonic activity appear. E, F, Small unit was a predominantly tonic medial rectus motoneuron identified antidromically. Note that the frequency during the movement in the ondirection in F (arrow) is less than during positions of fixation farther in the on-direction to the right in E. The small phasic activation of the predominantly tonic unit in F can be compared to the more prominent phasic activation of the larger unit during downward eye movement.
activity were m a x i m a l . These directions generally a g r e e d with k n o w n pulling directions o f the musclesS. 24. Classification o f unit activity. T h e r e were considerable differences in firing p a t t e r n s o f m o t o n e u r o n s . These differences were p r e s e n t in units r e c o r d e d in b o t h the nuclei a n d nerves. S o m e units h a d firing which was m o s t closely r e l a t e d to p o s i t i o n s o f fixation (tonic activity, Fig. 2A). O t h e r s fired with bursts o f spikes when the eye m o v e d into the o n - d i r e c t i o n (phasic activity, Fig. 2B), a n d t h e r e was n o activity associated with p o s i t i o n s o f fixation o v e r wide ranges. I n o t h e r units t h e r e was a m i x t u r e o f b o t h phasic a n d tonic c o m p o n e n t s (Fig. 2 C - F ) . The various types o f units f o r m e d a continu u m between phasic units o n one h a n d a n d tonic units on the o t h e r hand. F o r convenience in describing the different f u n c t i o n a l p r o p e r t i e s o f the individual units, we divided t h e m into 5 groups. Activity o f s o m e units was r e c o r d e d for over I h, a n d different stimuli were a p p l i e d to evoke various types o f eye m o v e m e n t s , b u t units never c h a n g e d their f u n c t i o n a l properties. O n l y when animals b e c a m e d r o w s y as Brain Research, 45 (1972) 561-568
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Fig. 3. Lower two traces are horizontal and vertical EOG. Immediately above is a dot display showing the instantaneous frequency (reciprocal of interspike interval) of unit firing• Unit activity used to trigger the frequency display is shown in the top trace of A. A, B, Tonic superior rectus or inferior oblique motoneuron. There was a step-like increase in frequency with each eye movement upward. This unit had a relatively high threshold. C, Predominantly tonic abducens motoneuron, activated when the eye moved to the right. The first eye movement to the left and up was associated with a decrease in frequency, but the unit did not entirely cease firing at this time. Subsequent saccades to the right were associated with a transient increase in firing. The maximum frequency during the first saccades was only slightly greater than during the final position of fixation on the right. D, Predominantly tonic abducens motoneuron active during eye movements to the left• Maximum frequencies during eye movements to the left were dependent on position and size of movement. E, Tonic-phasic motoneuron from the right abducens nucleus. The unit tended to reach maximum firing frequencies during each eye movement to the right, and had irregular tonic activity when the eye was on the right. F, Phasic unit firing during eye movement to the left. The time base is shown under each of the traces. The vertical bars show approximately 25 ° of deviation for both the horizontal and vertical EOGs.
e v i d e n c e d b y d r o o p i n g eyelids, r o v i n g eye m o v e m e n t s , a n d a n o v e r a l l d e c r e a s e in t h e m a x i m u m v e l o c i t y o f s a c c a d e s 13, d i d t h e r e l a t i o n s h i p b e t w e e n eye m o v e m e n t a n d u n i t activity change. Any such periods were not considered for analysis. There were no
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differences in types of motoneurons of different muscles so that all units were pooled in this description. A more complete description of differences in unit activity which led to the various subdivisions follows. The numbers in parentheses refer to the number of units of each type that were encountered. Tonic units (22). The frequency of tonic units increased in stepwise fashion at the onset of saccades in the on-direction (Figs. 2A, and 3A and B). The new frequencies were maintained until the next change in eye position. Transient changes in frequency during eye movements were limited to one or several interspike intervals (Fig. 3A). The lack of transient response in the neuron shown in Fig. 3A and B was not due to saturation, since the cell fired faster when the eye moved farther in the on-direction (Fig. 3B). When the eye moved in the off-direction, the frequency of these units decreased in a stepwise fashion (Fig. 3B) or with a transient change over a few intervals. The reduction in activity in the off-direction occurred before the onset of eye movement, showing that the units were not eye muscle afferents. There were both low (Fig. 2A) and high threshold tonic units (Fig. 3A and B). Predominantly tonic units (50). These were the most common units we encountered. They were always active during periods of fixation above threshold (Fig. 2C and D, and E and F (small unit); Fig. 3C, D). They generally had some phasic component during eye movements in the on-direction, but the transient change in activity was often small. The maximum frequency which these units reached was dependent not only on the size of the eye movement, but also on the position of the eyes when movement began. For example, these units generally did not reach maximum frequency during movement which began from the off-direction (Fig. 3C, D) and maximum frequencies were higher for saccades of the same size if they began farther in the on-direction (Fig. 3C, D). Maximum frequencies were higher during positions of fixation far in the on-direction (Fig. 2E, small unit) than during some saccades (Fig. 2F, small unit, arrow). Most of these units were not completely inhibited during movements in the off-direction (Figs. 2D, 3C), but this was not invariable (Fig. 3D). The decline in frequency in these units was often not entirely complete at the end of eye movement, and there was a slow reduction in frequency for 25-50 msec after the end of movement (Fig. 3D). Several predominantly tonic medial rectus motoneurons identified antidromically had conduction velocities of about 10 m/sec. Tonic-phasic units (31). These units had continuous activity during positions of fixation above threshold (Fig. 3E), but also had strong transient changes in activity during almost every rapid eye movement in the on-direction. Above threshold they tended to reach maximum frequency during all movements in which they were active (Fig. 3E). Thus eye position was not a strong factor in determining maximum firing frequencies during eye movement. The tonic activity of these ceils could either be regular or irregular (up to about 25 ~o of peak frequency; Fig. 3E). These cells were usually completely inhibited during movements in the off-direction. Predominantly phasic units (4). These units fired during eye movements, but had some activity associated with positions of fixation far in the on-direction (Fig. 2E, F, large unit). The threshold for the phasic response was much lower than for the tonic discharge (Fig. 2E, F), and the discharge rates during fixation periods were
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d a t a to their findings. H o w e v e r , they d i d n o t e t h a t there were m o t o n e u r o n s which were n o t fired by even the s t r o n g e s t a n g u l a r acceleration. M o s t m o t o n e u r o n s can p r o b a b l y be recruited u n d e r certain circumstances to aid in m o v i n g the eyes slowly o r r a p i d l y into the extremes o f gaze. H o w e v e r , o u r results show t h a t n o t all cells o r d i n a r i l y p e r f o r m similarly d u r i n g p o s i t i o n s o f fixation a n d r a p i d eye m o v e m e n t s . F r o m the qualitative characteristics it seems likely t h a t tonic units a r e m o r e closely related to m a i n t e n a n c e o f p o s i t i o n s o f fixation, p r e d o m i n a n t l y phasic a n d phasic units to m o v i n g the eyes, a n d p r e d o m i n a n t l y tonic a n d t o n i c - p h a s i c cells to b o t h functions. T o the extent t h a t the different types o f firing r e p r e s e n t different functions, i.e., h o l d i n g p o s i t i o n s o f fixation o r m o v i n g the eyes, then m o t o n e u r o n s o f the e x t r a o c u l a r muscles have different f u n c t i o n a l characteristics. S u p p o r t e d by N I H G r a n t NS-00294 a n d N I N D S C a r e e r R e s e a r c h D e v e l o p m e n t A w a r d 1K3-34,987 (B.C.). W e t h a n k L e o n a r d Z a b l o w a n d D i a n a C a b r e r a for assistance. Department o f Neurology, Mount Sinai School of Medicine, New York, N.Y. 10029 (U.S.A.)
VOLKER HENN* BERNARD COHEN
1 ASCHOrF, J. C., AND COHEN, B., Changes in saccadic eye movements produced by cerebellar cortical lesions, Exp. Neurol., 32 (1971) 123-133. 2 BACI-I-Y-RITA,P., AND ITO, F., In vivo studies on fast and slow muscle fibers in cat extraocular muscles, J. gen. 1;hysiol., 49 (1966) 1177-1198. 3 BAKER,R., ANDPRECHT, W., Electrophysiologlcalproperties of trochlear motoneurons as revealed by IVth nerve stimulation, Exp. Brain Res., 14 (1972) 127-157. 4 BJ6RKMANN,A., AND WOHLFART,G., Faseranalyse der Nn. oculomotorius, trochlearis und abducens des Menschen und des N. abducens verschiedener Tiere, Z. mikr.-anat. Forsch., 39 (1936) 631-641. 5 BOLDER, P., Co-operative action of extraocular muscles, Brit. d. Ophthal., 46 (1962) 397-403. 6 CHENG, K., AND BREININ, G. M., A comparison of the fine structure of extraocular and interosseus muscles in the monkey, Invest. Ophthal., 5 (1966) 535-549. 7 FUCHS,A., ANDLUSCHEI,E., Firing patterns of abducens neurons of alert monkeys in relationship to horizontal eye movement, J. Neurophysiol., 33 (1970) 382-392. 8 FucHs, A. F., AND LUSCHEI,E. S., The activity of single trochlear nerve fibers during eye movements in the alert monkey, Exp. Brain Res., 13 (1971) 78-89. 9 FUKUDA, M., Histological studies on the oculomotor nucleus of the rabbit. Jap. J. OphthaL, 8 (1964) 59--67. 10 HESS,A., ANDPILAR,G., Slow fibers in the extraocular muscles of the cat, J. Physiol. (Lond.), 169 (1963) 780--798. 11 HORCHOLLE,G., AND TY~-DUMONT, S., Activit6s unitaires des neurones vestibulaires et oculomoteurs au cours du nystagmus, Brain Research, 5 (1968) 16-31. 12 KELLER, E. L., AND ROBINSON,D. A., Absence of a stretch reflex in extraocular muscles of the monkey, J. Neurophysiol., 34 (1971) 908-919. 13 KOMATSUZAKI,A., HARRIS, H. E., ALPERT,J., AND COHEN, B., Horizontal nystagmus of rhesus monkeys, Acta oto-laryng. (Stockh.), 67 (1969) 535-551. 14 MAYR,R., STOCKINGER,L., ANDZENKER,W., Elektronmikroskopische Untersuchungen an unterschiedlich innervierten Muskelfasern der iiusseren Augenmuskulatur des Rhesusaffen, Z. Zellforsch., 75 (1966) 434-452. 15 MILLER,J. E., Cellular organization of rhesus extraocular muscle, Invest. Ophthal., 6 (1967) 18-39. * Present address: Kantonsspital, Neurologische Universitiitsklinik, 8006 Ziirich, Switzerland. Brain Research, 45 (1972) 561-568
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16 PEACHEY,L., The structure of the extraocular muscle fibers of mammals. In P. BACH-Y-RITA,C. ('. COLLINS AND J. HYDE (Eds.), The Control of Eye Movements, Academic Press, New York, 1971, pp. 47-66. 17 PRECHT, W., RICHTER, A., AND GRIPPO, J., Responses of neurones in cat's abducens nuclei to horizontal angular acceleration, Pfliigers Arch. ges. Physiol., 309 (1969) 285-309. 18 REINHART,R. J., AND ZUBER, B. L., Abducens nerve signals controlling saccadic eye movements in the cat, Brain Research, 34 (1971) 331-344. 19 ROaINSON,D. A., Oculomotor unit behavior in the monkey, J. Neurophysiol., 33 (1970) 393-404. 20 SCHAEFER,K. P., Die Erregnungsmuster einzelner Neurone des Abducens-Kernes beim Kaninchen, Pfliigers Arch. ges. Physiol., 284 (1965) 31-52. 21 SCHILLER, P. H., The discharge characteristics of single units in the oculomotor and abducens nuclei of the unanesthetized monkey, Exp. Brain Res., 10 (1970) 347-362. 22 SIEBECK, R., AND KRUGER, P., Die histologische Struktur der/iusseren Augenmuskeln als Ausdruck ihrer Funktion, Albrecht v. Graefes Arch. Ophthal., 156 (1955) 637-651. 23 TSUCH1DA, U., Uber die Ursprungskerne der Augenbewegungsnerven und die mit diesen in Beziehung stehenden Bahnen im Mittel- und Zwischenhirn. Normal-anatomische, embryologische, pathologisch-anatomische und vergleichend-anatomische Untersuchungen, Arb. Hirnanat. Inst. Ziirich, 2 0906) 1-205. 24 VOLKMANN, A. W., Zur Mechanik der Augenmuskeln, Bet. Saechs. Ges. Wiss., 21 (1869) 28-69. 25 WARWICk, R., Representation of the extraocular muscles in the oculomotor nuclei of the monkey, J. comp. Neurol., 98 (1953) 449-503. 26 YAMANAKA,Y., AND BACH-Y-RITA, P., Conduction velocities in the abducens nerve correlated with vestibular nystagmus in cats, Exp. Neurol., 20 (1968) 143-155. 27 YAMANAKA,Y., AND BACH-Y-RITA, P., Relations between extraocular muscle contraction and extension times in each phase of nystagmus, Exp. Neurol., 27 (1970) 57-65. (Accepted August 8th, 1972)
Brain Research, 45 (1972) 561-568
SHORT COMMUNICATIONS
Eye muscle motor neurons with different functional characteristics There are differences in the size of eye muscle motoneuronsg, 2z and in the diamete# and conduction velocity of their axonsZ, 26. There are also diverse types of eye muscle fibers ranging from fast singly-innervated twitch fibers to slow multi-innervated fibers with graced contractionsZ,~,10,14-16, 22. Therefore, recent reportsT,S,12, 21 that all oculomotor, abducens, and trochlear motoneurons have similar activity patterns are somewhat surprising. In this paper we report attempts to determine whether this was correct by studying the qualitative characteristics of motoneurons of monkeys during spontaneous saccades and positions of fixation. Unit activity was recorded in the oculomotor and abducens nuclei and nerves of alert restrained monkeys (Macaca mulatta) with tungsten microelectrodes of 2-10 M f L The monkeys looked about spontaneously and moved their eyes in all directions. Deviations were generally within 4- 20 ° of the midposition with horizontal eye movements predominating. Whenever units were held long enough, objects were introduced into the peripheral fields to induce larger gaze shifts. Electrodes were inserted into the brain through an implanted plug in a 0.8 mm guide tube, and were advanced with a hydraulic microdrive (Trent Wells, Southgate, Calif.). Stable recordings of action potentials between 100 #V and 5 mV over periods of 20 sec to 100 min were analyzed. In one animal a bipolar stainless steel electrode for antidromic stimulation was implanted in the IIIrd nerve using stereotaxic techniques. Horizontal and vertical eye movements and positions of fixation were recorded with platinum needle electrodes using DC-coupled amplifiers. The electrooculogram (EOG) was calibrated using horizontal and vertical optokinetic and rotatory stimuli of known velocitieslA3. Eye movements and unit data were stored on FM magnetic tape and displayed on a storage oscilloscope. The frequency of unit activity was determined by a small, general purpose digital computer or by a frequency meter. The latter gave a pulse at the time of each spike whose voltage was proportional to the reciprocal of the preceding interspike interval. Electrolytic lesions were later, made above and below recording sites to identify electrode tracks in histological sections. Identification of motoneurons and general characteristics. Recordings were taken from 32 units in the oculomotor nerve. An electrode track through the oculomotor nerve (IIIrd nerve) rootlets is shown in Fig. 1A. Units in the nerve which changed their activity before the onset of eye movements were considered to be axons of motoneurons. Activity of 138 units was also recorded in the oculomotor and abducens nuclei. The trochlear nucleus was not explored. Unit activity in the nerve differed in a number of respects from activity in the motor nuclei: action potentials in the nerve had no inflection on the rising phase; no cells or fibers were found which were loosely coupled to eye movement or which changed activity during eye movement in all directions; and units associated with eye movements in different directions and with blinks were packed closely together without the spatial separation found in the oculomotor nucleus. An electrode track through the oculomotor nucleus is shown in Fig. lB. The site of recording was about 5.5 mm distant to that in Fig. 1A. Eighty-nine of the 138
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Fig. 1. A, B, Electrode tracks through the rootlets of the oculomotor nerve (A, I11 R, arrow) and oculomotor nucleus (B, III Nuc). In A lesions (L) were later made above and below the recording site at the time of killing. The dentato-thalamic fibers (dt) and habenulo-interpedunctdar tract (thi) are also labelled. The section in A is in the A ÷ 8 vertical stereotaxic plane and in B is in the A I 3 plane. The two recording locations are separated by 5.5 ram. Weil and cresyl violet stains.
units encountered in the m o t o r nuclei were believed to be motoneurons. Several were identified by antidromic stimulation. The rest were presumptively identified because o f the site o f recording and because their activity patterns were the same as units in the m o t o r nerve. These included units associated with abduction (lateral rectus units), adduction (medial rectus units), and depression and adduction (inferior rectus units). Superior rectus and inferior oblique m o t o n e u r o n s are not readily separated on the basis o f site o f recording and direction o f eye movement, since cells responsible for m o v e m e n t o f both eyes up and to the same side are located in adjacent parts o f one o c u l o m o t o r nucleus 2a. Consequently, they were grouped together. The approximate locations o f units associated with different muscles in the m o t o r nuclei corresponded to the description o f Warwick 25. Forty-nine o f 138 units from the I I I r d and VIth nerve nuclei had activity patterns which were different f r o m motoneurons. These were considered to be prem o t o r or central units. Some were ' m i r r o r units'. They had most o f the characteristics o f motoneurons, but their o n - o f f direction was just the reverse o f adjacent m o t o r units. These included units in the abducens nucleus which were associated with adduction, or in the o c u l o m o t o r nucleus associated with abduction. They may correspond to interneurons described in the eye muscle m o t o r nuclei of cat 11,17. M o t o r units generally had increases or decreases in firing frequencies 5-8 msec before the onset o f eye movement. F o r units with transient increases in activity during eye movements (see below), the firing rates decreased about 5-8 msec before the movement ended 7,s,18. The reverse was true during transient decreases in activity. M o s t units had some change in activity during eye movements in almost every direction, but there was a preferred plane o f movement, the o n - o f f direction, in which changes in Brain Research, 45 (1972) 561-568
SHORT COMMUNICATIONS
563
it_ C
D
111'! l ! !!!!!!l ! ' l l ! !l l i l 1 l l llllllllllllllt!ll!illlqlllLll/ III Iliilllllllllllllllllllllllll~ IlllllllUlllllUmlllllllllllllllllllltll Iil i i
i
iiii Ill IIIIII ,,i,,,u~liiii~ ili~illiliLili111,,,,.
.....
.......... litlllllllllllllllllli [~" .......... ,
_
~ 1
25 °
100 nv~
Fig. 2. Top trace, unit recording; middle trace, horizontal EOG; bottom trace, vertical EOG. Eye movement to the right and up caused upward deflection of the 2nd and 3rd traces, respectively, in this and in Fig. 3. Basis for identification of motoneurons is given in text. A, Tonic inferior rectus motoneuron. B, Phasic medial rectus motoneuron. C, D, Predominantly tonic medial rectus motoneuron. Inhibition during the movement in the off-direction in D was accomplished over one or several interspike intervals, and the unit was not completely inhibited except when firing near threshold. E, F, Large unit was a predominantly phasic inferior rectus motoneuron which fired with a burst of spikes during downward eye movements over wide ranges of deviation. Only when the eye was strongly depressed (F) did tonic activity appear. E, F, Small unit was a predominantly tonic medial rectus motoneuron identified antidromically. Note that the frequency during the movement in the ondirection in F (arrow) is less than during positions of fixation farther in the on-direction to the right in E. The small phasic activation of the predominantly tonic unit in F can be compared to the more prominent phasic activation of the larger unit during downward eye movement.
activity were m a x i m a l . These directions generally a g r e e d with k n o w n pulling directions o f the musclesS. 24. Classification o f unit activity. T h e r e were considerable differences in firing p a t t e r n s o f m o t o n e u r o n s . These differences were p r e s e n t in units r e c o r d e d in b o t h the nuclei a n d nerves. S o m e units h a d firing which was m o s t closely r e l a t e d to p o s i t i o n s o f fixation (tonic activity, Fig. 2A). O t h e r s fired with bursts o f spikes when the eye m o v e d into the o n - d i r e c t i o n (phasic activity, Fig. 2B), a n d t h e r e was n o activity associated with p o s i t i o n s o f fixation o v e r wide ranges. I n o t h e r units t h e r e was a m i x t u r e o f b o t h phasic a n d tonic c o m p o n e n t s (Fig. 2 C - F ) . The various types o f units f o r m e d a continu u m between phasic units o n one h a n d a n d tonic units on the o t h e r hand. F o r convenience in describing the different f u n c t i o n a l p r o p e r t i e s o f the individual units, we divided t h e m into 5 groups. Activity o f s o m e units was r e c o r d e d for over I h, a n d different stimuli were a p p l i e d to evoke various types o f eye m o v e m e n t s , b u t units never c h a n g e d their f u n c t i o n a l properties. O n l y when animals b e c a m e d r o w s y as Brain Research, 45 (1972) 561-568
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Fig. 3. Lower two traces are horizontal and vertical EOG. Immediately above is a dot display showing the instantaneous frequency (reciprocal of interspike interval) of unit firing• Unit activity used to trigger the frequency display is shown in the top trace of A. A, B, Tonic superior rectus or inferior oblique motoneuron. There was a step-like increase in frequency with each eye movement upward. This unit had a relatively high threshold. C, Predominantly tonic abducens motoneuron, activated when the eye moved to the right. The first eye movement to the left and up was associated with a decrease in frequency, but the unit did not entirely cease firing at this time. Subsequent saccades to the right were associated with a transient increase in firing. The maximum frequency during the first saccades was only slightly greater than during the final position of fixation on the right. D, Predominantly tonic abducens motoneuron active during eye movements to the left• Maximum frequencies during eye movements to the left were dependent on position and size of movement. E, Tonic-phasic motoneuron from the right abducens nucleus. The unit tended to reach maximum firing frequencies during each eye movement to the right, and had irregular tonic activity when the eye was on the right. F, Phasic unit firing during eye movement to the left. The time base is shown under each of the traces. The vertical bars show approximately 25 ° of deviation for both the horizontal and vertical EOGs.
e v i d e n c e d b y d r o o p i n g eyelids, r o v i n g eye m o v e m e n t s , a n d a n o v e r a l l d e c r e a s e in t h e m a x i m u m v e l o c i t y o f s a c c a d e s 13, d i d t h e r e l a t i o n s h i p b e t w e e n eye m o v e m e n t a n d u n i t activity change. Any such periods were not considered for analysis. There were no
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differences in types of motoneurons of different muscles so that all units were pooled in this description. A more complete description of differences in unit activity which led to the various subdivisions follows. The numbers in parentheses refer to the number of units of each type that were encountered. Tonic units (22). The frequency of tonic units increased in stepwise fashion at the onset of saccades in the on-direction (Figs. 2A, and 3A and B). The new frequencies were maintained until the next change in eye position. Transient changes in frequency during eye movements were limited to one or several interspike intervals (Fig. 3A). The lack of transient response in the neuron shown in Fig. 3A and B was not due to saturation, since the cell fired faster when the eye moved farther in the on-direction (Fig. 3B). When the eye moved in the off-direction, the frequency of these units decreased in a stepwise fashion (Fig. 3B) or with a transient change over a few intervals. The reduction in activity in the off-direction occurred before the onset of eye movement, showing that the units were not eye muscle afferents. There were both low (Fig. 2A) and high threshold tonic units (Fig. 3A and B). Predominantly tonic units (50). These were the most common units we encountered. They were always active during periods of fixation above threshold (Fig. 2C and D, and E and F (small unit); Fig. 3C, D). They generally had some phasic component during eye movements in the on-direction, but the transient change in activity was often small. The maximum frequency which these units reached was dependent not only on the size of the eye movement, but also on the position of the eyes when movement began. For example, these units generally did not reach maximum frequency during movement which began from the off-direction (Fig. 3C, D) and maximum frequencies were higher for saccades of the same size if they began farther in the on-direction (Fig. 3C, D). Maximum frequencies were higher during positions of fixation far in the on-direction (Fig. 2E, small unit) than during some saccades (Fig. 2F, small unit, arrow). Most of these units were not completely inhibited during movements in the off-direction (Figs. 2D, 3C), but this was not invariable (Fig. 3D). The decline in frequency in these units was often not entirely complete at the end of eye movement, and there was a slow reduction in frequency for 25-50 msec after the end of movement (Fig. 3D). Several predominantly tonic medial rectus motoneurons identified antidromically had conduction velocities of about 10 m/sec. Tonic-phasic units (31). These units had continuous activity during positions of fixation above threshold (Fig. 3E), but also had strong transient changes in activity during almost every rapid eye movement in the on-direction. Above threshold they tended to reach maximum frequency during all movements in which they were active (Fig. 3E). Thus eye position was not a strong factor in determining maximum firing frequencies during eye movement. The tonic activity of these ceils could either be regular or irregular (up to about 25 ~o of peak frequency; Fig. 3E). These cells were usually completely inhibited during movements in the off-direction. Predominantly phasic units (4). These units fired during eye movements, but had some activity associated with positions of fixation far in the on-direction (Fig. 2E, F, large unit). The threshold for the phasic response was much lower than for the tonic discharge (Fig. 2E, F), and the discharge rates during fixation periods were
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d a t a to their findings. H o w e v e r , they d i d n o t e t h a t there were m o t o n e u r o n s which were n o t fired by even the s t r o n g e s t a n g u l a r acceleration. M o s t m o t o n e u r o n s can p r o b a b l y be recruited u n d e r certain circumstances to aid in m o v i n g the eyes slowly o r r a p i d l y into the extremes o f gaze. H o w e v e r , o u r results show t h a t n o t all cells o r d i n a r i l y p e r f o r m similarly d u r i n g p o s i t i o n s o f fixation a n d r a p i d eye m o v e m e n t s . F r o m the qualitative characteristics it seems likely t h a t tonic units a r e m o r e closely related to m a i n t e n a n c e o f p o s i t i o n s o f fixation, p r e d o m i n a n t l y phasic a n d phasic units to m o v i n g the eyes, a n d p r e d o m i n a n t l y tonic a n d t o n i c - p h a s i c cells to b o t h functions. T o the extent t h a t the different types o f firing r e p r e s e n t different functions, i.e., h o l d i n g p o s i t i o n s o f fixation o r m o v i n g the eyes, then m o t o n e u r o n s o f the e x t r a o c u l a r muscles have different f u n c t i o n a l characteristics. S u p p o r t e d by N I H G r a n t NS-00294 a n d N I N D S C a r e e r R e s e a r c h D e v e l o p m e n t A w a r d 1K3-34,987 (B.C.). W e t h a n k L e o n a r d Z a b l o w a n d D i a n a C a b r e r a for assistance. Department o f Neurology, Mount Sinai School of Medicine, New York, N.Y. 10029 (U.S.A.)
VOLKER HENN* BERNARD COHEN
1 ASCHOrF, J. C., AND COHEN, B., Changes in saccadic eye movements produced by cerebellar cortical lesions, Exp. Neurol., 32 (1971) 123-133. 2 BACI-I-Y-RITA,P., AND ITO, F., In vivo studies on fast and slow muscle fibers in cat extraocular muscles, J. gen. 1;hysiol., 49 (1966) 1177-1198. 3 BAKER,R., ANDPRECHT, W., Electrophysiologlcalproperties of trochlear motoneurons as revealed by IVth nerve stimulation, Exp. Brain Res., 14 (1972) 127-157. 4 BJ6RKMANN,A., AND WOHLFART,G., Faseranalyse der Nn. oculomotorius, trochlearis und abducens des Menschen und des N. abducens verschiedener Tiere, Z. mikr.-anat. Forsch., 39 (1936) 631-641. 5 BOLDER, P., Co-operative action of extraocular muscles, Brit. d. Ophthal., 46 (1962) 397-403. 6 CHENG, K., AND BREININ, G. M., A comparison of the fine structure of extraocular and interosseus muscles in the monkey, Invest. Ophthal., 5 (1966) 535-549. 7 FUCHS,A., ANDLUSCHEI,E., Firing patterns of abducens neurons of alert monkeys in relationship to horizontal eye movement, J. Neurophysiol., 33 (1970) 382-392. 8 FucHs, A. F., AND LUSCHEI,E. S., The activity of single trochlear nerve fibers during eye movements in the alert monkey, Exp. Brain Res., 13 (1971) 78-89. 9 FUKUDA, M., Histological studies on the oculomotor nucleus of the rabbit. Jap. J. OphthaL, 8 (1964) 59--67. 10 HESS,A., ANDPILAR,G., Slow fibers in the extraocular muscles of the cat, J. Physiol. (Lond.), 169 (1963) 780--798. 11 HORCHOLLE,G., AND TY~-DUMONT, S., Activit6s unitaires des neurones vestibulaires et oculomoteurs au cours du nystagmus, Brain Research, 5 (1968) 16-31. 12 KELLER, E. L., AND ROBINSON,D. A., Absence of a stretch reflex in extraocular muscles of the monkey, J. Neurophysiol., 34 (1971) 908-919. 13 KOMATSUZAKI,A., HARRIS, H. E., ALPERT,J., AND COHEN, B., Horizontal nystagmus of rhesus monkeys, Acta oto-laryng. (Stockh.), 67 (1969) 535-551. 14 MAYR,R., STOCKINGER,L., ANDZENKER,W., Elektronmikroskopische Untersuchungen an unterschiedlich innervierten Muskelfasern der iiusseren Augenmuskulatur des Rhesusaffen, Z. Zellforsch., 75 (1966) 434-452. 15 MILLER,J. E., Cellular organization of rhesus extraocular muscle, Invest. Ophthal., 6 (1967) 18-39. * Present address: Kantonsspital, Neurologische Universitiitsklinik, 8006 Ziirich, Switzerland. Brain Research, 45 (1972) 561-568
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16 PEACHEY,L., The structure of the extraocular muscle fibers of mammals. In P. BACH-Y-RITA,C. ('. COLLINS AND J. HYDE (Eds.), The Control of Eye Movements, Academic Press, New York, 1971, pp. 47-66. 17 PRECHT, W., RICHTER, A., AND GRIPPO, J., Responses of neurones in cat's abducens nuclei to horizontal angular acceleration, Pfliigers Arch. ges. Physiol., 309 (1969) 285-309. 18 REINHART,R. J., AND ZUBER, B. L., Abducens nerve signals controlling saccadic eye movements in the cat, Brain Research, 34 (1971) 331-344. 19 ROaINSON,D. A., Oculomotor unit behavior in the monkey, J. Neurophysiol., 33 (1970) 393-404. 20 SCHAEFER,K. P., Die Erregnungsmuster einzelner Neurone des Abducens-Kernes beim Kaninchen, Pfliigers Arch. ges. Physiol., 284 (1965) 31-52. 21 SCHILLER, P. H., The discharge characteristics of single units in the oculomotor and abducens nuclei of the unanesthetized monkey, Exp. Brain Res., 10 (1970) 347-362. 22 SIEBECK, R., AND KRUGER, P., Die histologische Struktur der/iusseren Augenmuskeln als Ausdruck ihrer Funktion, Albrecht v. Graefes Arch. Ophthal., 156 (1955) 637-651. 23 TSUCH1DA, U., Uber die Ursprungskerne der Augenbewegungsnerven und die mit diesen in Beziehung stehenden Bahnen im Mittel- und Zwischenhirn. Normal-anatomische, embryologische, pathologisch-anatomische und vergleichend-anatomische Untersuchungen, Arb. Hirnanat. Inst. Ziirich, 2 0906) 1-205. 24 VOLKMANN, A. W., Zur Mechanik der Augenmuskeln, Bet. Saechs. Ges. Wiss., 21 (1869) 28-69. 25 WARWICk, R., Representation of the extraocular muscles in the oculomotor nuclei of the monkey, J. comp. Neurol., 98 (1953) 449-503. 26 YAMANAKA,Y., AND BACH-Y-RITA, P., Conduction velocities in the abducens nerve correlated with vestibular nystagmus in cats, Exp. Neurol., 20 (1968) 143-155. 27 YAMANAKA,Y., AND BACH-Y-RITA, P., Relations between extraocular muscle contraction and extension times in each phase of nystagmus, Exp. Neurol., 27 (1970) 57-65. (Accepted August 8th, 1972)
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