Otolith and semicircular canal inputs to single vestibular neurons in cats

Transcription

1 Biological Sciences in Space, Vol.15 No.4 (2001): Uchino, Y Jpn. Soc. Biol. Sci. Space Otolith and semicircular canal inputs to single vestibular neurons in cats Yoshio Uchino Department of Physiology, Tokyo Medical University, Shinjuku, Shinjuku-ku, Tokyo , Japan. Introduction Otolith organs mainly sense linear acceleration, whereas semicircular canals mainly sense angular acceleration. The utricular macula senses horizontal linea acceleration and tilts of the head, while the saccular macula senses vertical linear acceleration. Both the receptors usually respond together during natural head movements. It was observed that some vestibular relay neurons receive inputs from some of the semicircular canals and otolith organs, while others do not, when natural stimuli were applied in alert cats (Baker et al. 1984; Curthoys and Halmagyi 1995; Kasper et al. 1988; Manzoni et al. 1993; Markham 1968; Schor and Miller 1982; Wilson and Melvill Jones 1979). By following the electrical stimulation of individual nerve branches of the vertical semicircular canals and otolitic nerves, synaptic potentials were recorded in the target vestibular neurons (Graf and Ezure 1986; Graf et al. 1983; Isu et al. 1988, 1990; Kasahara and Uchino 1974; Straka and Dieringer 1996; Uchino and Hirai 1984; Uchino et al. 1981, 1982, 1986, 1988, 1990, 1997b, 1999; Uchino and Isu 1992a, 1992b; Wilson et al. 1978), extraocular motoneurons, (Ezure and Graf 1984; Highstein 1973, 1988; Isu et al. 1988, 2000; Sasaki et al. 1991; Uchino et al. 1980, 1994a, 1996) and neck motoneurons (Bolton et al. 1992; Ikegami et al. 1994; Isu et al. 1988, 1990; Shinoda et al. 1994; Sugiuchi et al. 1995; Uchino et al. 1994b, 1997a; Wilson and Maeda 1974). Syaptic potentials evoked in target vestibular interneurons after stimulation of individual canal and otolith nerves had the same latecy range and same axonal pathways, so it is possible that single vestibular interneurons send information from different receptors to extraocular and neck motoneurons. In this paper, we studied the convergence of the vertical posterior semicircular canal and otolith inputs, and of the horizontal semicircular canal and otolith inputs on single vestibular neurons, which were categorized according to their innervating targets. Vestibular neurons were classiffied as VS neurons (Vestibulospinal proper neurons), VO neurons (Vestibulo-Ocular proper neurons), VOS (Vestibulo-Oculo- Spinal neurons sending axon collaterals both to the extraocular motoneuron pools and to the spinal cord) and Received: September 10, Address for correspondence: Yoshio Uchino Department of Physiology, Tokyo Medical University, Shinjuku, Shinjuku-ku, Tokyo , Japan. V neurons (vestibular nucleus neurons without axons either to the oculomotor nuclei or the spinal cord) on the basis of whether or not they responded antidromically to stimulation of the oculomotor nuclei and the spinal cord (Isu and Yokota 1983; Uchini and Isu 1992a, 1992b; Uchino et al. 1988, 1990). The results in this paper have been summarized in previous papers (Kushiro et al. 2000; Sato et al. 2000; Uchino et al. 1997b, 2000; Zakir et al. 2000; Zhang et al. 2000). Methods Experiments were performed on cats in conformity with the Guiding Principles for the Care and Use of Animals in the Field of Physiological Sciences; The Physiological Society of Japan, Each cat was initially anesthetized with Ketamine hydrochloride followed by halothane and nitrous oxide inhalation. The cat was then decerebrated at the intercollicular level. Temporal and occipital craniotomy and laminectomies were performed. The caudal part of the cerebellum was aspirated to expose the floor of the fourth ventricle. Rectal temperature was maintained at 37.5 C. Blood pressure was monitored and maintained above 100 mmhg by intravenous infusion of a 5-10% glucose solution. The animal was paralyzed with pancuronium bromide, and artificially ventilated. In order to test for convergence of the posterior semicircular canal (PC) and saccular (SAC) nerves, the PC and utricular (UT) nerves, the horizontal semicircular canal (HC) and SAC nerves, the HC and UT nerves, or the SAC and UT nerves on single neurons in the vestibular nuclei, pairs of fine silver electrodes (acupuncture needles), that were insulated except for 0.25 ~ 0.5 mm at the tip, were placed into individual nerves in the left inner ear. The other vestibular nerve branches which were not to be stimulated were transected in the inner ear (Sasaki et al. 1991; Uchino et al. 1994a, 1997a). The inter-electrode distance was approximately 0.8 mm. The inner ear was drained of liquid using a small piece of twisted cotton, and the electrodes were fixed to the occipital bone. To prevent the spread of stimulus current, these nerves and electrodes were covered with a warm semisolid paraffin-vaseline mixture. Cathodal or anodal current pulses of 150~200 ms duration were applied to the saccular, utricular and PC nerves at a rate of 2-3 Hz. Monopolar tungsten electrodes were inserted into the caudal end of the oculomotor nuclei, and medial (M) and lateral (L) vestibulospinal tract (VST) at the C1 or C2 segment. The same monopolar electrodes were inserted into the bilateral C8 ~ Th1 and L3 segments (Rapoport et al. 1977) in some cats. The animal was suspended by hip pins and a clamp on the T1 vertebra.

2 Otolith and Canal Convergence Table 1 Whole number and percentage ( ) of convergence and non-comvergence vestibular neurons in each series of experiments. PC/SAC (Sato et al. 2000), PC/UT (Zakir et al. 2000), HC/SAC and HC/UT (Zhang et al. 2000) and SAC/UT (Kushiro et al. 2000). Total Convergence PC-alone SAC-alone PC/SAC (33) 55 (38) 41 (29) PC/UT (33) 79 (49) 28 (18) HC/SAC (17) 56 (45) 48 (38) HC/UT (15) 34 (43) 34 (43) SAC/UT (36) 65 (46) 24 (17) Total (28) Field potentials were recorded from the vestibular nuclei with glass micropipettes containing 2 M NaCl saturated with Fast Green dye. The threshold for stimulation of the SAC, UT, PC and HC nerves to evoke N1 field potentials, which are due to monosynaptic activation of secondary vestibular neurons (Precht an Shimazu 1965; Shimazu and Precht 1966), ranged from 5 to 45 µa. The threshold was comparable with that reported in previous papers (Uchino et al. 1994a, 1996, 1997a, 1997b). Intracellular recordings were performed mainly from lateral and descending vestibular neurons using micropipettes filled with 2 M K citrate, with a resistance of 3-10 MΩ. Synaptic potentials were recorded following selective stimulation of the vestibular nerve branches. Antidromic activation was also tested after stimulation of the oculomotor nuclei and spinal cord to determine the innervating targets of the neurons. Results We studied the convergence of both afferents of the PC/SAC, PC/UT, HC/SAC, HC/UT and SAC/UT nerves on single vestibular neurons. More than 600 vestibular neurons were classified as VS, VO, VOS and V neurons. To determine inputs to single vestibular neurons, the PC, HC, SAC and UT nerves were stimulated at an intensity of approximately times the threshold of the N1 potential (XN1T). These stimulus intensities were confirmed to be below the intensity of current spread to the other vestibular nerve branches (Uchino et al. 1994a, 1994b, 1996, 1997b). Excitatory postsynaptic potentials (EPSPs), with latencies of 1.4 msec after stimulation of individual nerves, were of a monosynaptic nature (Kasahara and Uchino 1974; Kushiro et al. 2000; Mano et al. 1968; Precht and Shimazu 1965; Sato et al. 1996, 1997; Sato et al. 2000; Shimazu and Precht 1966; Uchino et al. 1994a, 2000; Zakir et al. 2000; Zhang et al. 2000). All but one of the inhibitory (I) PSPs in the VO, VOS, VS and V neurons were of a disynaptic nature ( 1.5 msec) in response to stimulation of individual nerves (Kasahara and Uchino 1974; Kushiro et al. 2000; Precht and Shimazu 1965; Sato et al. 1996, 1997, 2000; Shimazu and Precht 1966; Uchino et al. 1994a, 1996, 1997a, 1997b, 2000; Zakie et al. 2000; Zhang et al. 2000). Of the total 648 vestibular neurons recorded in the series of experiments, the percentage convergence of PCactivated convergent neurons (PC/SAC 33%, PC/ UT 33%) was higher than that of HC-activated convergent neurons (HC/SAC 17%, HC/UT 15%) (Table 1). The percentage of SAC/UT inputs on single vestibular neurons was similar to the PC- and otolithconvergent neurons (Table 1). VS neurons Two hundred and seventy-six VS neurons were studied. As shown in Table 2, 82 VS neurons with convergent inputs were found. In the vertical semicircular canal and otolith, more than 30% of the VS neurons received inputs from both (Table 2). The percentage of convergent VS neurons was higher than that of the horizontal and otolith system (Table 2). Some convergent VS neurons were activated monosynaptically following stimulation of PC/SAC (13/ 26, Sato et al. 2000), PC/UT (4/16, Zakir et al. 2000), HC/ SAC (5/9, Zhang et al. 2000), HC/UT (3/8, Zhang et al. 2000), SAC/UT (11/23, Kushiro et al. 2000). In the remaining VS neurons, polysynaptic PSPs were evoked from one or both. The ratios of the PC-, HC-, SAC- and UT-alone VS neurons to those of convergent neurons are shown in Table 2. Axons of about two-thirds (36/56), (36/ Table 2 Number and percentage ( ) of convergence and non-convergence VS neurons in each series of experiments. (PC/SAC, Sato et al. 2000; PC/UT, Zakir et al. 2000; HC/SAC and HC/UT, Zhang et al and SAC/UT, Kushiro et al. 2000). VS neurons Total VS neurons Convergence PC-alone SAC-alone PC/SAC (43) 16 (26) 19 (31) PC/UT (32) 24 (48) 10 (20) HC/SAC (17) 19 (37) 24 (46) HC/UT (24) 10 (29) 16 (47) SAC/UT (29) 44 (56) 12 (15) Total (30)

3 Uchino, Y. Table 3 Number and percentage ( ) of convergence and non-convergence VO neurons in each series of experiments. (PC/SAC, Sato et al. 2000; PC/UT, Zakir et al. 2000; HC/SAC and HC/UT, Zhang et al and SAC/UT, Kushiro et al. 2000). VO neurons Total VO neurons Convergence PC-alone SAC-alone PC/SAC (14) 12 (86) 0 (0) PC/UT (63) 3 (38) 0 (0) HC/SAC (0) 2 (100) 0 (0) HC/UT (33) 2 (33) 2 (33) SAC-alone SAC/UT (33) 2 (66) 0 (0) Total (30) 50), (31/52), (17/34) and the majority (62/75) of VS neurons (including both convergent and non-convergent) descended in to the LVST, in studies of PC/SAC, PC/UT, HC/SAC, HC/UT and SAC/UT, respectively. Remaining VS neurons (20/56), (14/50), (21/52), (17/34) and (13/25) descended in to the, in studies of PC/SAC, PC/UT, HC/SAC, HC/UT and SAC/UT, respectively. VO neurons We studied 33 VO neurons after stimulation of each vestibular nerve (Table 3). As shown in Table 3, the total number and the number of VO were low (33/648, 5%). Only 2 non-convergent VO neurons were activated in response to stimulation of the UT nerve (Table 3). No HC/ SAC convergent, no SAC-alone and no UT-alone (PC/UT and SAC/UT) VO neurons were found in a series of experiments (Sato et al. 2000; Kushiro et al. 2000; Zakir et al. 2000) (Table 3). Synaptic inputs on convergent and nonconvergenr VO neurons following selective stimulation of the vestibular nerve branches were polysynaptic. Monosynaptic inputs on VO neurons were only from PC and HC nerves, except for a few UT-activated VO neurons (Zhang et al. 2000). VOS neurons In our series, we studied the input convergence on 70 VOS neurons (Table 4). The percentage of convergence of the vertical semicircular canal and otolith, and horizontal semicircular canal and otolith on single VOS neurons were similar to those of convergence patterns of the VS neurons, except for the descending pathway of the VS neurons (Table 2, 3 & 4). Almost all the VOS neurons descended in the (Kushiro et al. 2000; Sato et al. 2000; Uchino and Isu 2000; Zakir et al. 2000; Zhang et al. 2000). V neurons These neurons may send axons to the contralateral, as well as ipsilateral vestibular nuclei, the reticular formation and the cerebellum. However, these V neurons were not activated after stimulation of the oculomotor nuclei and the spinal cord at an intensity of ~ 2mA. Sixty-seven neurons had convergent inputs from tested pairs (Table 5). Properties of convergence and non-convergence neurons were similar to those of VS neurons (Table 2). The role of these V neurons in vestibular functioning remains a subject for future study. Discussion Convergence of primary afferents UT-alone from the PC and otolith, HC and otolith, and SAC and UT afferents on single vestibular neurons were studied, classifying vestibular neurons as VS, VO, VOS and V neurons according to their antidromical activation from the oculomotor nuclei and spinal cord. In this paper, five series of experiments including convergence of PC/SAC (Sato et al. 2000), PC/ UT (Zakir et al. 2000), HC/SAC (Zhang et al. 2000), HC/ UT (Zhang et al. 2000) and SAC/UT (Kushiro et al. 2000) inputs on single vestibular neurons were included. In the series, there were few otolith-activated neurons sending axons to the oculomotor nuclei (VO and VOS). In patrticular, secondary vestibular neurons monosynaptically activated by otoloth stimulation rarely sent axons to the oculomotor nuclei (i.e. VO or VOS neurons), but mostly sent axons exclusively to the spinal cord (i.e. VS neurons). Vestibulo-ocular reflex pathway from the canals and otolith organs Recently, we have found monosynaptic connections from the UT nerve to motoneurons and interneurons in the abducens nucleus (Imagawa et al. 1995; Uchino et al. 1994a). We also studied connections from the UT nerve to motoneurons of all extraocular muscles (Sasaki et al. 1991; Uchino et al. 1994a, 1996). These studies elucidated that the disynaptic pathway from the UT nerve to extraocular motoneurons, except for abducens motoneurons and interneurons, is poorly organized. Stimulation of the UT nerve evoked depolarizing and hyperpolarizing potentials with longer latency in contralateral and ipsilateral medial rectus motoneurons, and complex potentials with longer latencies in ipsilateral inferior oblique and contralateral trochlear motoneurons (Sasaki et al. 1991; Uchino et al. 1996). These longer latency reflex pathways were considered to be trisynaptic or more synapse-mediated on the bases of our latency analyses (Sasaki et al. 1991; Uchino et al. 1981, 1982, 1994a, 1996). Recently, we also studied connections between SAC afferents and individual motoneurons of all the extraocular muscles (Isu et al. 2000). The results showed that the sacculo-ocular reflex pathways have more poorly organized connections than the utriculo-

4 Otolith and Canal Convergence Table 4 Number and percentage of convergence and non-convergence VOS neurons in each series of experiments. (PC/SAC, Sato et al. 2000; PC/UT, Zakir et al. 2000; HC/SAC and HC/UT, Zhang et al and SAC/UT, Kushiro et al. 2000). VOS neurons Total VOS neurons Convergence PC-alone SAC-alone PC/SAC (43) 7 (50) 1 (7) PC/UT (33) 14 (59) 2 (8) HC/SAC (27) 6 (40) 5 (33) HC/UT (13) 2 (25) 5 (63) SAC/UT (67) 2 (22) 1 (11) Total (36) ocular connectivity. Axonal projections of UT nerve-activated vestibular neurons to the oculomotor nuclei and the spinal cord were also studied. Almost no second order vestibular neurons, monosynaptically activated by UT nerve stimulation, had ascending branches to the oculomotor nuclei (Sato et al. 1996). Few VO and VOS neurons, which are activated monosynaptically from the UT nerve or the SAC nerve, were found in the present studies (Kushiro et al. 2000; Sato et al. 2000; Zakir et al. 2000; Zhang et al. 2000). The present results, together with our previous data (Isu et al. 2000; Sasaki et al. 1991; Uchino et al. 1994a, 1996), strongly suggest that the three neuron arcs from the UT and SAC nerves to the extraocular motoneurons, except for abducens motoneurons, are very poorly organized. This suggestion was confirmed in our series of experiments (Kushiro et al. 1999, 2000; Sato et al. 2000; Zakir et al. 2000) Vestibulocollic reflex pathway from the canals and otolith organs Using selective stimulation of the semicircular canal nerves and SAC and UT nerves, connections from canal nerves (Isu et al. 1988, 1990; Shinoda et al. 1994; Sugiuchi et al. 1995; Uchino and Hirai 1984; Uchino and Isu 1992a, 1992b; Uchino et al. 1988) UT nerves (Bolton et al. 1992; Ikegami et al. 1994), and SAC nerves (Uchino et al. 1997a) to neck extensor and flexor motoneurons were studied. SAC and UT nerve inputs in motoneurons innervating the sternocleidomastoid muscles (SCM) were also studied (Kushiro et al. 1999). These data are summarized in Table 6. Ipsilateral SCM motoneurons generated SPs with the same range of (i.e., disynaptic) latency after activation of the PC, SAC and UT nerves through the same pathway, i.e.,. Similarly, contralateral SCM motoneurons frequently generated disynaptic EPSPs after PC and UT nerve stimulation via the same pathway (), although the pathway from the HC nerve to the rotator motoneurons is still unknown. Contralateral extensor motoneurons also generated identical potentials (disynaptic EPSPs) after HC and SAC nerve stimulation. In our series of experiments, we found some second order VS neurons which were activated monosynaptically from both the PC, HC, SAC and UT nerves (Kushiro et al. 2000; Sato et al. 2000; Zakir et al. 2000). It is likely that their mediation partly contributes to the generation of disynaptic potentials to neck motoneurons. It is hypothesized that these convergent VS neurons function to stabilize the head position when the head is inclined near the normal (i.e., upright) position, since convergent inputs from the semicircular canal and the otolith organ make them sensitive to head inclination. VS neurons receiving either semicircular or otolithic input seem to contribute to specific reflexes. Neck motoneurons, in particular, in which different types of postsynaptic potential are evoked after PC, HC and otolithic nerve stimulation (see Table 6), must be innervated by non-convergent neurons. However, note that VS neurons, which are classified as non-convergent neurons receiving otolithic input, but no PC and HC inputs in the present study may have received anterior canal inputs and mediated both inputs to the neck motoneurons. Table 5 Number and percentage of convergence and non-convergence V neurons in each series of experiments. (PC/SAC, Sato et al. 2000; PC/UT, Zakir et al. 2000; HC/SAC and HC/UT, Zhang et al and SAC/UT, Kushiro et al. 2000). V neurons Total V neurons Convergence PC-alone SAC-alone PC/SAC (24) 20 (37) 21 (39) PC/UT (31) 38 (49) 16 (20) HC/SAC (14) 29 (52) 19 (34) HC/UT (3) 19 (59) 12 (38) SAC/UT (43) 19 (39) 9 (18) Total (25)

5 Uchino, Y. Table 6 Basic excitatory and inhibitory connections from PC-, HC-, SAC- and UT-activated vestibular neurons to neck motoneurons. The lower rows indicate pathways. EP, excitatory postsynaptic potential;, inhibitory postsynaptic potential; LVST, lateral vestibulospinal tract;, medial vestibulospinal tract. Input Ipsilateral Contralateral Muscles PC HC SAC UT PC HC SAC UT Extensor (Biv. Cervicis EP EP EP EP * & complex) LVST not tested not tested Flexor EP not tested EP EP not tested * * (Longus Capitis) not tested LVST not tested LVST Rotator (sternocleidomastoideus) not tested EP EP not tested No Effect EP Summary Convergence of both afferents from the PC/SAC, PC/ UT, HC/SAC, HC/UT and SAC/UT on single vestibular neurons was studied using intercellular recording. Vestibular neurons were classified as VO neurons (vestibulo-ocular proper neurons), VOS (vestibulo-oculospinal neurons), VS neurons ( vestibulospinal proper neurons) and V neurons (vestibular neurons without axons to the oculomotor nuclei or the spinal cord) on the basis of whether or not they responded antidromically to stimulation of the oculomotor nuclei and the spinal cord. Of the total 648 vestibular neurons recorded in a series of experiments on convergence, the PC/SAC, PC/UT, HC/SAC, HC/UT and SAC/UT afferents were 47/143 (33%), 53/160 (33%), 21/125 (17%), 12/80 (15%) and 51/140 (36%), respectively. Twenty-six of the 47, 16/50, 9/52, 8/34 and 23/29 convergent neurons were identified as being VS-type neurons in PC/SAC, PC/UT, HC/SAC, HC/UT and SAC/ UT, respectively. Only 33/648 (5%) VO neurons sent axons to the oculomotor nuclei (Table 1). The percentage of convergence of VS neurons was higher than that of neurons sending axons to the oculomotor nuclei (VO and VOS). In conclusion, the convergence of canal and otolith inputs likely contributes mainly to vestibulospinal reflexes, including the vestibulocollic reflex, by sending inputs to the neck and other muscles during head inclination which creates the combined stimuli of angular and linear acceleration. Acknowledgments I thank Drs. Sato H, Imagawa M, Sasaki M, Meng H, Zhang X, Ono S, Kushiro K, Zakir M and Isu N for collaboration in the series of experiments. I also thank Miss K. Takayama for secretarial assistance. This study was supported by a research grant from the Japan Space Forum promoted by NASDA (National Space Development Agency of Japan). References Baker J, Goldberg J, Hermann G, Peterson B (1984) Optimal response planes and canal convergence in secondary neurons in vestibular nuclei of alert cats. Brain Res., 294, Bolton, P. S., Endo, K., Goto, T., Imagawa, M., Sasaki, M., Uchino, Y., Wilson, V.J. (1992) Connections between utricular nerve and dorsal neck motoneurons of the decerebrate cat. J. Neurophysiol., 67, Curthoys, I.S., Halmagyi, G. (1995) Vestibular compensation: a review of the oculomotor, neural, and clinical consequences of unilateral vestibular loss. J. Vestibular Res., 5, Ezure, K., Graf, W. (1984) A quantitative analysis of the spatial organization of the vestibulo-ocular reflexes in lateral- and frontal-eyed animals-ii. Neuronal networks underlying vestibulo-oculomotor coordination. Neuroscinece, 12, Graf, W., Ezure, K. (1986) Morphology of vertical canal related second order vestibular neurons in the cat. Exp. Brain Res., 63, Graf, W., McCrea, R.A., Baker, R. (1983) Morphology of posterior canal related secondary vestibular neurons in the rabbit and cat. Exp. Brain Res., 52, Highstein, S.M. (1973) The organization of the vestibulooculomotor and trochlear reflex pathways in the rabbit. Exp. Brain Res., 17, Highstein, S.M. (1988) Sensory-to-motor transformations in the vestibular system. Brain Behav. Evol., 31, Ikegami, H., Sasaki, M., Uchino, Y. (1994) Connections between utricular nerve and neck flexor motoneurons of the decerebrate cats. Exp. Brain Res., 98, Imagawa, M., Isu, N., Sasaki, M., Endo, K., Ikegami, H., Uchino, Y. (1995) Axonal projections of utricular afferents to the vestibular nuclei and abducens nucleus in cats. Neurosci. Lett., 186, Isu, N., Graf, W., Sato, H., Kushiro, K., Zakir, M., Imagawa, M., Uchino, Y. (2000) Sacculo-ocular reflex connectivity in cats. Exp. Brain Res., 131, Isu, N., Sakuma, A., Hiranuma, K., Ichikawa, T., Uchino, Y. (1990) Localization and synaptic effects of inhibitory vestibulocollic neurons activated by the posterior semicircular canal nerve in the cat. Neurosci. Lett., 119, Isu, N., Uchino, Y., Nakashima, H., Satoh, S., Ichikawa, T., Watanabe, S. (1988) Axonal trajectories of posterior canalactivated secondary vestibular neurons and their coactivcation of extraocular and neck flexor motoneurons in the cat. Exp. Brain Res., 70, Isu, N., Yokota, J. (1983) Morphophysiological study on the divergent projection of axon collaterals of medial vestibular nucleus neurons in the cat. Exp. Brain Res., 53,

6 Otolith and Canal Convergence Kasahara, M., Uchino, Y. (1974) Bilateral semicircular canal inputs to neurons in cat vestibular nuclei. Exp. Brain Res., 20, Kasper, J., Schor, R.H., Wilson, V.J. (1988) Response of vestibular neurons to head rotations in vertical planes. I. Response to vestibular stimulation. J. Neurophysiol., 60, Kushiro, K., Zakir, M., Ogawa, Y., Sato, H., Uchino, Y. (1999) Saccular and utricular inputs to sternocleidomastoid motoneurons of decerebrated cats. Exp. Brain Res., 126, Kushiro, K., Zakir, M., Sato, H., Ono, S., Ogawa, Y., Meng, H., Zhang, X., Uchino, Y. (2000) Saccular and Utricular inputs to single vestibular neurons in cats. Exp. Brain Res., 131, Mano, N., Oshima, T., Shimazu, H. (1968) Inhibitory commissural fibers interconnecting the bilateral vestibular nuclei. Brain Res., 8, Manzoni, D., Pompeiamo, O., Marchand, A.R. (1993) Temporal response properties of lumbar-projecting vestibulospinal neurons to roll tilt in decerebrate cats. Pflugers Arch., 423, Markham, C.H. (1968) Midbrain and contralateral labyrinth influences on brain stem vestibular neurons in the cat. Brain Res., 9, Precht, W., Shimazu, H. (1965) Functional connections of tonic and kinetic vestibular neurons with primary vestibular afferents. J. Neurophysiol., 28, Rapoport, S., Susswein, A., Uchino, Y., Wilson, V.J. (1977) Properties of vestibular neurones projecting to neck segments of the cat spinal cord. J. Physiol., 268, Sasaki, M., Hiranuma, K., Isu, N., Uchino, Y. (1991) Is there a three neuron arc in the cat utriculo-trochlear pathway? Exp. Brain Res., 86, Sato, H., Endo, K., Ikegami, H., Imagawa, M., Sasaki, M., Uchino, Y. (1996) Properties of utricular nerve-activated vestibulospinal neurons in cats. Exp. Brain Res., 112, Sato, H., Imagawa, M., Isu, N., Uchino, Y. (1997) Properties of saccular nerve-activated vestibulospinal neurons in cats. Exp. Brain Res., 116, Sato, H., Imagawa, M., Kushiro, K., Zakir, M., Uchino, Y. (2000) Convergence of posterior semicircular canal and saccular inputs in single vestibular nuclei in cats. Exp. brain Res., 131, Schor, R.H., Miller, A.D. (1982) Relationship of cat vestibular neurons to otolith-spinal reflexes. Exp. Brain Res., 47, Shimazu, H., Precht, W. (1966) Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway. J. Neurophsyiol., 29, Shinoda, Y., Sugiuchi, Y., Futami, T., Ando, N., Kawasaki, T. (1994) Input patterns and pathways from the six semicircular canals to motoneurons of neck muscles. I. The multifidus muscle group. J. Neurophysiol., 72, Straka, H., Dieringer, N. (1996) Uncrossed disynaptic inhibiton of second-order vestibular neurons and its interaction with monosynaptic excitation from vestibular nerve afferent fibers in the frog. J. Neurophysiol., 76, Sugiuchi, Y., Izawa, Y., Shinoda, Y. (1995) Trisynaptic inhibiotion from the contralateral vertical semicircular canal nerves to neck motoneurons mediated by spinal commissural neurons. J. Neurophysiol., 73, Uchino, Y., Hirai, N. (1984) Axon collaterals of anterior semicircular canal-activated vestibular neurons and their coactivation of extraocular and neck motoneurons in the cat. Neuroscience Res., 1, Uchino, Y., Hirai, N., Suzuki, S. (1982) Branching pattern and properties of vertical- and horizontal-related excitatory vestibuloocular neurons in the cat. J. Neurophysiol., 48, Uchino, Y., Hirai, N., Suzuki, S., Watanabe, S. (1981) Properties of secondary vestibular neurons fired by stimulation of ampullary nerve of the vertical, anterior or posterior, semicercular canals in the cat. Brain Res., 223, Uchino, Y., Ichikawa, T., Isu, N., Nakashima, H., Watanabe, S. (1986) The commissural inhibition on secondary vestibuloocular neurons in the vertical semicircular canal systems in the cat. Neurosci. Lett., 70, Uchino, Y., Ikegami, H., Sasaki, M., Endo, K., Imagawa, M., Isu, N. (1994a) Monosynaptic and disynaptic connections in the utriculo-ocular reflex arc of the cat. J. Neurophysiol., 71, Uchino, Y., Isu, N. (1992a) Properties of vestibulo-ocular and/or vestibulocollic neurons in the cat. In: Berthoz A, Graf W, Vidal PP (eds) Heda-neck sensory motor systems, New York, Oxford, Oxford University Press. pp Uchino, Y., Isu, N. (1992b) Properties of inhibitory vestibuloocular and vestibulo-collic neurons in the cat. In: Shimazu H, Shinoda Y (eda) Vestibular and brain stem control of eye, head and body movements Tokyo/S. Karger, Basel, pp Uchino, Y., Isu, N., Ichikawa, T., Satoh, S., Watanabe, S. (1988) Properties and localization of the anterior semicircular canalactivated vestibulocollic neurons in the cat. Exp. Brain Res., 71, Uchino, Y., Isu, N., Sacuma, A., Ichikawa, T., Hiranuma, K. (1990) Axonal trajectories of inhibitory vestibulocollic neurons activated by the anterior semicircular canal nerve and their synaptic effects on neck motoneurons in the cat. Exp. Brain Res., 82, Uchino, Y., Sasaki, M., Sato, H., Imagawa, M., Suwa, H., Isu, N. (1996) Utriculoocular reflex arc of the cat. J. Neurophysiol., 76, Uchino, Y., Sato, H., Imagawa, M., Sasaki, M., Ikegami, H. (1994b) The sacculo-neck reflex arc of the decerebrate cat. In: Taguchi K, Igarashi M, Mori S (eds) Vestibular and neural front Amsterdam Elsevier (International congress series 1070) pp Uchino, Y., Sato, H., Kushiro, K., Zakir, M., Imagawa, M., Ogawa, Y., Katsuta, M., Isu, N. (1999) Cross-striolar and commissural inhibition in the otolith system. Ann. N.Y. Acad. Sci., 871, Uchino, Y., Sato, H., Kushiro, K., Zakir, M., Isu, N. (2000) Canal and otorith inputs to single vestibulaer neurons in cats. Archives Italiennes de Biologie, 138, Uchino, Y., Sato, H., Sasaki, M., Imagawa, M., Ikegami, H., Isu, N., Graf, W. (1997a) Sacculocollic reflex arcs in cats. J. Neurophysiol., 77,

7 Uchino, Y. Uchino, Y., Sato, H., Suwa, H. (1997b) Excitatory and inhibitory inputs from saccular afferents single vestibular neurons in the cat. J. Neurophysiol., 78, Uchino, Y., Suzuki, S., Watanabe, S. (1980) Vertical semicircular canal inputs to cat extraocular motoneurons. Exp. Brain Res., 41, Wilson, V.J., Gacek, R.R., Uchino, Y., Susswein, A.J. (1978) Properties of central vestibular neurons fired by stimulation of the saccular nerve. Brain Res., 143, Wilson, V.J., Maeda, M. (1974) Connections between semicircular canals and neck motoneurons in the cat. J. Neurophysiol., 37, Wilson, V.J., Melvill Jones, G. (1979) Mammalian Vestibular Physiology. New York and London, Plenum Press. Zakir, M., Kushiro, K., Ogawa, Y., Sato, H., Uchino, Y. (2000) Convergence patterns of th posterior semicircular canal and utricular inputs in single vestibular neurons in cats. Exp. Brain Res., 132, Zhang, X., Zakir, M., Meng, H., Sato, H., Uchino, Y. (2000) Convergence from otolith and horizontal semicircular canal nerves on cat single vestibular neurons. Soc for Neurosci Abstr 30: Part 1-6.