| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Submitted 12 May 2004; accepted in final form 6 September 2004
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
). In the intermediate and deep layers, the SC contains neurons that show a burst of spikes before and during saccades (Schiller and Körner 1971; Wurtz and Goldberg 1972) and send their axons to the paramedian pontine reticular formation (PPRF) (Grantyn and Grantyn 1982; Izawa et al. 1999; Moschovakis et al. 1998; Scudder et al. 1996). Stimulation of the PPRF produces and a lesion of the PPRF eliminates horizontal conjugate eye movements (Bender and Shanzer 1964; Büttner-Ennever and Büttner 1988; Cohen and Komatsuzaki 1972; Cohen et al. 1968; Henn et al. 1984). Two groups of neurons that show a burst of spikes before and during saccades have been reported in the brain stem: medium-lead burst neurons (MLBNs) and long-lead burst neurons (LLBNs) (Luschei and Fuchs 1972). MLBNs include excitatory (EBNs) and inhibitory burst neurons (IBNs); the former are located in the PPRF (Cohen and Henn 1972; Keller 1974; Luschei and Fuchs 1972) and the latter are in the paramedian pontomedullary reticular formation (PPMRF) (Hikosaka and Kawakami 1977; Yoshida et al. 1982). Scudder et al. (1996) showed that the SC neurons identified as LLBNs projected to the PPRF and the PPMRF.
Precht et al. (1974) and later Grantyn and Grantyn (1976) analyzed the synaptic connections between the SC and abducens motoneurons, using intracellular recording, and showed that abducens motoneurons received excitation from the contralateral SC and inhibition from the ipsilateral SC. This excitation from the contralateral SC was mainly disynaptic or trisynaptic to abducens motoneurons, whereas the inhibition from the ipsilateral SC was mainly trisynaptic. Our previous study reanalyzed these connections and showed that the excitation and inhibition from the SC were mainly disynaptic to abducens motoneurons (Izawa et al. 1999). On the other hand, previous physiological studies reported that MLBNs in the PPRF were activated either monosynaptically (Chimoto et al. 1996) or disynaptically by LLBNs from the SC (Raybourn and Keller 1977). Similarly MLBNs in the PPMRF were monosynaptically activated from the SC (Chimoto et al. 1996). The direct projection from the SC to the PPMRF has been confirmed anatomically (Harting 1977; Olivier et al. 1993).
In the rostral part of the SC, one group of neurons that discharge during fixation and pause during most saccades has been reported (Munoz and Guitton 1989, 1991; Munoz and Wurtz 1993a, b; Peck 1989), and the "fixation zone" that contains such neurons (Guitton 1991; Munoz and Istvan 1998; Munoz and Wurtz 1995b) has been hypothesized to prevent saccades via excitatory projections to pause neurons (PNs) in the nucleus raphe interpositus on the midline within the PPRF (Büttner-Ennever and Horn 1994; Büttner-Ennever et al. 1988; Evinger et al. 1977; Langer and Kaneko 1984, 1990; Ohgaki et al. 1987, 1989; Strassman et al. 1987). The remaining part of the SC is called the "saccade zone" (Gandhi and Keller 1999; Munoz and Istvan 1998), and contains burst and build-up neurons (Anderson et al. 1998; Basso and Wurtz 1998; Munoz and Wurtz 1995a). It has been suggested that 2 regions in the SC have reciprocal functions: the rostral zone maintains fixation, whereas the more caudal region participates in the generation of saccades (Goldberg and Wurtz 1972; Munoz and Guitton 1989, 1991; Munoz and Istvan 1998; Munoz and Wurtz 1993a, b, 1995a, b; Munoz et al. 1991; Paré and Guitton 1994; Paré et al. 1994; Peck 1989). However, the functional independence of the rostral pole of the SC is not necessarily accepted (Gandhi and Keller 1999).
Functionally, when something interesting appears in the visual field and the line of sight is shifted to that object, 2 kinds of different neural mechanisms are thought to be involved: one makes an accurate saccade to the object of concern, and the other suppresses saccades toward other objects that appear in the visual field but are not of interest at the moment. If these 2 different systems of reciprocal functions exist in the SC, the pattern of connections from the rostral and caudal parts of the SC to burst neurons in the brain stem should be different, but detailed information on synaptic inputs from the superior colliculi (SCs) to these burst neurons is not yet available.
The present study was performed to determine neural connections from the rostral and caudal parts of the SC to IBNs projecting to the abducens nucleus, using intracellular recording and staining methods in the anesthetized cat. The results show that the caudal parts of the contralateral and ipsilateral SC exert monosynaptic excitation and disynaptic inhibition by contralateral IBNs on IBNs, respectively. To the contrary, the rostral SC exerts disynaptic inhibition on IBNs on both sides, most likely via PNs in the nucleus raphe interpositus.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
). Animal experimentation was conducted in accordance with "Policies on the Use of Animals and Humans in Neuroscience Research," revised and approved by the Society for Neuroscience in 1995, and "Guiding Principles for the Care and Use of Animals in the Field of Physiological Sciences" (The Physiological Society of Japan, revised in 2001). The experimental protocol was approved by the Animal Care Committee of Tokyo Medical and Dental University. The animals were initially anesthetized with ketamine hydrochloride (Ketalar, Parke-Davis; 25 mg/kg, intramuscularly [im]) followed by 
-chloralose (40–45 mg/kg, intravenously [iv], initial dose, supplemented with additional doses of 10–25 mg/kg, iv throughout the remainder of the experiment). During recording, the animals were paralyzed by the iv administration of pancuronium bromide (Mioblock, Organon, Oss, The Netherlands), and artificially ventilated with end-tidal CO2 held at 35–40 mmHg. The heart rate was constantly monitored by an electrocardiogram. The body temperature was kept at 37.0–38.5°C by a heating pad. The abducens nerve was detached from the muscle and mounted on a bipolar hook electrode for electrical stimulation. The bone over the parietal and occipital cortex was removed, and the cerebral cortex was removed by suction bilaterally to introduce stimulating electrodes into the SCs under direct visual observation. Usually, 4 concentric bipolar stimulating electrodes (inner and outer diameter, 0.1 and 0.3 mm; interelectrode distance along the longitudinal axis, 0.5 mm) were arranged rostrocaudally at 1.0–1.2 mm intervals along the presumed horizontal meridian of the motor map in the SC on both sides (McIlwain 1986). Their tips were positioned in the intermediate or deep layer (1.5–2.0 mm deep from the surface) of the SC (Izawa et al. 1999; Kawamura and Hashikawa 1978; Moschovakis and Karabelas 1985). The vermis overlying the fourth ventricle was removed by suction to facilitate intracellular recording from neurons in the abducens nucleus and the IBN region.
To identify the abducens nucleus and the IBN region electrophysiologically, antidromic field potentials were mapped in the abducens nucleus region, while stimulating the abducens nerve (Maeda et al. 1971b; Shinoda and Yoshida 1974). For antidromic identification of IBNs and the analysis of inputs from the contralateral IBN region to IBNs, separate electrode arrays were placed in the abducens nucleus and the IBN region contralateral to the recording site. These electrode arrays consisted of 4 monopolar electrodes (100 µm in diameter) insulated except at the tip, which were glued together around a pillar, so that the tips of the 4 electrodes were arranged dorsoventrally at 1-mm intervals. Stimulus currents were delivered between 2 adjacent tips, and the pillar was grounded to reduce stimulus artifacts. To further reduce stimulus artifacts, biphasic pulses were used; a cathodal rectangular pulse of 0.2-µs duration was immediately followed by a smaller anodal pulse of 0.1-µs duration. The amplitude of the latter was adjusted to achieve optimal cancellation of artifacts (Asanuma and Arnold 1975). Negative pulses of 0.2-ms duration were delivered at 100–500 µA for stimulation of the SC, and at <200 µA (usually <100 µA) for stimulation of the abducens nucleus and the IBN region. The positions of the stimulating electrodes in the brain stem were marked by passing negative currents of 20 µA for 20 s after each experiment, and the stimulated sites in the SC, abducens nucleus, and IBN region were histologically confirmed on sections stained with thionine.
Glass microelectrodes for intracellular recording were filled with 0.4 M KCl or 2 M K-citrate and had a resistance of 10–15 M
. Glass microelectrodes for both intracellular recording and staining were filled with 7% horseradish peroxidase (HRP, Toyobo, Osaka, Japan) in 0.4 M KCl, and had a resistance of 20–40 M (Shinoda et al. 1986, 1992). To morphologically confirm the identification of electrophysiologically identified IBNs, penetrated neurons were iontophoretically injected with HRP. After a survival time of about 16 h, the animals were deeply anesthetized with pentobarbital sodium (Nembutal, Abbott, Baar, Switzerland; 50 mg/kg, iv) and perfused with 2 L of 10% sucrose phosphate buffer (pH = 7.4) followed by 2 L of a fixative solution containing 2% paraformaldehyde and 1% glutaraldehyde in 4% sucrose phosphate buffer. Serial frozen sections 80 µm thick were cut from the brain stem and treated for HRP by the heavy metal–intensification method (Adams 1981). The details of the intracellular staining method with HRP and the method used for reconstruction of the axonal trajectories of single neurons were previously described (Shinoda et al. 1986, 1992).
The location of IBNs terminating on contralateral abducens motoneurons was determined using the transneuronal labeling method (Sugiuchi et al. 1995). Wheat germ agglutinin–horseradish peroxidase (WGA–HRP; (Toyobo) was injected into the abducens nerve (Izawa et al. 1999). After 4–6 days, the animals were anesthetized with ketamine hydrochloride (25 mg/kg, im) followed by pentobarbital sodium (50 mg/kg, iv), and perfused with 2 L of 10% sucrose phosphate buffer (pH = 7.4) followed by 2 L of a fixative solution containing 4% paraformaldehyde and 0.05% glutaraldehyde with 0.2% picric acid in 4% sucrose phosphate buffer. Serial coronal sections 75 µm thick were cut on a freezing microtome. The method of histological processing for WGA–HRP staining was previously described in detail (Izawa et al. 1999). Labeled neurons were plotted under a microscope using a camera lucida system and a computer-assisted plotting and reconstruction program (Neurolucida, MicroBrightField, Colchester, VT).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
To penetrate IBNs efficiently and stimulate the IBN region properly at a low stimulus intensity, we determined the exact location of IBNs using a transneuronal-labeling method in 4 cats. Figure 1 shows a typical example of the distribution of labeled neurons in the midbrain, pons, and medulla after injection of WGA–HRP into the left abducens nerve. Heavily labeled neurons in the left abducens nucleus were regarded as retrogradely labeled abducens motoneurons (Fig. 1C, sections 8 and 9), whereas many lightly labeled neurons in the brain stem were considered to be labeled transneuronally (Fig. 1, A–C). On the side ipsilateral to the injected abducens nerve (Fig. 1C), labeled neurons were distributed in the PPRF from the level of the rostral end of the abducens nucleus to about 2.5 mm rostral, 0.3–2.0 mm lateral from the midline, and 0.5–2.3 mm deep from the floor of the fourth ventricle (small dots in the pontine region in Fig. 1, A and B), the vestibular nuclei [mainly the magnocellular part of the medial vestibular nucleus defined by Gerrits et al. (1985), and the superior vestibular nucleus], the nucleus prepositus hypoglossi, and in and around the oculomotor nucleus (OMN) (Fig. 1C). On the contralateral side (Fig. 1C), transneuronally labeled neurons were found in the vestibular nuclei (mainly the magnocellular part of the medial vestibular nucleus), the nucleus prepositus hypoglossi, its adjacent ventral reticular formation, in and around the OMN, and the PPMRF, the region caudomedial to the caudal part of the abducens nucleus at 0.4–1.3 mm lateral from the midline and 0.5–2.5 mm deep from the floor of the fourth ventricle (large dots in Fig. 1, A and B). This last region corresponds to the region where IBNs were found during the quick phase of vestibular nystagmus (Curthoys et al. 1981; Hikosaka and Kawakami 1977) and during saccades (Yoshida et al. 1982). Similar results were obtained from all 4 cats. Based on these anatomical data, we could accurately determine recording and stimulation sites in the IBN region relative to the abducens nucleus, which was identified by recording typical negative antidromic field potentials (Baker et al. 1975; Maeda et al. 1971b; Shinoda and Yoshida 1974) at the beginning of each experiment.
|
To analyze synaptic inputs from the SCs to IBNs, we searched for neurons in the IBN region about 0.8 mm lateral from the midline. A previous study showed that tectofugal axons arising from the contralateral SC make contacts on IBNs that terminate on and inhibit contralateral abducens motoneurons (Izawa et al. 1999). Based on these findings, we considered the following criteria for the identification of penetrated neurons as IBNs: 1) Neurons should be located in the PPMRF region (see Fig. 1, A–C) (Chimoto et al. 1996; Curthoys et al. 1981; Hikosaka and Kawakami 1977; Strassman et al. 1986; Yoshida et al. 1982). 2) They should be activated antidromically by stimulation of the contralateral abducens nucleus (Fig. 2 B) (Hikosaka and Kawakami 1977; Hikosaka et al. 1978, 1980; Yoshida et al. 1982). 3) They should receive short-latency (mainly monosynaptic) excitatory input from the contralateral SC (Fig. 2C) (Chimoto et al. 1996; Izawa et al. 1999).
|
Many of these axon terminals made apparent contacts with counterstained cells in the abducens nucleus. Among the 25 stained neurons, 22 had axon branches with terminal boutons in the abducens nucleus and their other axon branches in the contralateral PPRF, PPMRF, vestibular nuclei, and nucleus prepositus hypoglossi. The remaining 3 neurons were poorly stained and axon branches were observed only in the abducens nucleus. The projection sites of these stained neurons were in good accordance with those of IBNs identified physiologically in alert animals (Hikosaka and Kawakami 1977), and their morphological features were consistent with those of IBNs described in previous studies (Strassman et al. 1986; Yoshida et al. 1982). Accordingly, this morphological result confirmed that the neurons that satisfied the above 3 electrophysiological criteria could be regarded as IBNs. In neurons that satisfied these 3 criteria, we usually observed disynaptic inhibition from the ipsilateral caudal SC (Fig. 2D), and therefore we added this property to the above criteria.
Because the firing pattern of these neurons during saccades could not be examined in the present anesthetized preparations, we regarded neurons that satisfied these 4 criteria as IBNs, and we used only the electrophysiological criteria to identify IBNs at later stages of the experiments. However, we could not use these criteria in experiments in which a midline section between the IBN regions was made to interrupt axons of IBNs projecting to the contralateral side. In such experiments, the criterion of antidromic activation was not used. Instead, we selected neurons that received monosynaptic excitation from the contralateral caudal SC because a previous study showed that abducens motoneurons received disynaptic inhibition from the ipsilateral SC by the contralateral IBNs and axon terminals of tectoreticular neurons directly contacted with contralateral IBNs (Izawa et al. 1999).
Synaptic inputs from the superior colliculi on both sides to IBNs
To uncover the properties of synaptic inputs from the rostral and caudal parts of the SC to IBNs, we examined the effects of stimulation on IBNs at 4 rostrocaudal sites along the horizontal meridian of the motor map in each SC. The resting membrane potentials of IBNs ranged from –40 to –75 mV (mean ± SD, –52 ± 15 mV, n = 75). Latencies of antidromic spikes evoked by stimulation of the contralateral abducens nucleus ranged from 0.4 to 1.1 ms (0.6 ± 0.2 ms, n = 62).
Figure 3 shows a typical example of the pattern of synaptic inputs from the bilateral SCs to an IBN. Stimulation of the ipsilateral SC evoked hyperpolarizations (Fig. 3B, 1–4), whereas stimulation of the contralateral SC evoked depolarizations (Fig. 3C, 5–8). The hyperpolarizations and depolarizations usually increased because the stimulation sites were more caudal in the SC. In addition, the most rostral site in the contralateral SC was different from the more caudal sites in that its stimulation evoked depolarization followed by small hyperpolarization (Fig. 3C5). Single stimuli evoked only a small depolarization (Fig. 3C, 7 and 8) and hyperpolarization (Fig. 3B4). On the other hand, double stimuli in the rostral pole could evoke large postsynaptic potentials (PSPs) as a result of temporal facilitation at an interneuronal level because most PSPs, especially hyperpolarizations, were di- or polysynaptic (see following text).
|
|
). Furthermore, this procedure was also used to determine whether the depolarizations were EPSPs or disinhibition resulting from a decrease in IPSPs. Because the depolarizations were not affected, they were regarded as EPSPs (Fig. 5C, 7 and 8) (Eccles 1964).
|
; Shinoda et al. 1976, 1981, 1982, 1987).
|
), most of the contralateral SC-evoked EPSPs in IBNs could be regarded as monosynaptic. In IBNs, IPSPs evoked by stimulation of the contralateral rostral SC had latencies of 1.4–2.8 ms (1.9 ± 0.3 ms, n = 41) (Fig. 6F). Most of these IPSPs were considered to be disynaptic from the SC because their latencies were about 0.8 ms longer than those of the monosynaptic EPSPs in IBNs (Fig. 6E). In abducens motoneurons, the latencies of SC-evoked EPSPs were 0.7–2.2 ms (1.5 ± 0.3 ms, n = 71) (Fig. 6I). These potentials were elicited at disynaptic latencies from the SC and are most likely mediated by EBNs in the PPRF (Izawa et al. 1999). On the other hand, the latencies of SC-evoked IPSPs were 1.4–2.4 ms (1.8 ± 0.2 ms, n = 69) (Fig. 6J), and were again primarily disynaptic. Most likely these are mediated by IBNs in the PPMRF (Izawa et al. 1999). In brief, IBNs received larger monosynaptic excitation from the more caudal parts of the contralateral SC and disynaptic inhibition from the most rostral part of it.
SYNAPTIC INPUTS TO IBNS FROM THE IPSILATERAL SC.
Figure 7 shows typical examples of PSPs in an IBN and an abducens motoneuron evoked by stimulation of the ipsilateral SC. Stimulation of both the rostral and caudal parts of the ipsilateral SC evoked hyperpolarizations in the IBN (Fig. 7B, 1–4) and the abducens motoneuron (Fig. 7D, 1–4). The hyperpolarizations in the IBN evoked by both the rostral and caudal stimulation were regarded as IPSPs because the injection of Cl– into the cell reversed the hyperpolarizations to depolarizations in the IBN (Fig. 7C). In abducens motoneurons, the IPSPs decreased with more rostral SC stimulation and only small IPSPs, if any, were evoked from the most rostral SC (Fig. 7D, 1–4) (Izawa et al. 1999). A similar tendency was also observed in IBNs (Figs. 4C, 2–4 and 7B, 2–4) but, unlike the abducens motoneurons, the IPSPs were always evoked by stimulation of the most rostral site (Figs. 3B1, 4C1, and 7B1) and were often as large as or larger than those evoked by stimulation of the next caudal site in the ipsilateral SC.
|
), and were 0.8 ms longer on average than those of SC-evoked monosynaptic EPSPs in IBNs. In brief, ipsilateral stimulation of both the rostral and caudal SC produced disynaptic inhibition in IBNs, whereas contralateral stimulation of the caudal SC produced monosynaptic excitation and that of the most rostral SC produced disynaptic inhibition in IBNs.
Sectioning of unilateral tectoreticular axons
To determine the pathways from the SC to IBNs, we sectioned tectoreticular axons in 4 cats (Fig. 8). A unilateral transverse section was made on the right side at a level about 2 mm rostral to the rostral end of the abducens nucleus (Fig. 8, A and E) to interrupt tectoreticular fibers connecting the SC and the PN region (Curthoys et al. 1981; Evinger et al. 1977, 1982; Ohgaki et al. 1987, 1989). The size of the transections (n = 4) was 1.5–2.0 mm wide from the midline in the transverse plane and 5.0–6.5 mm deep from the surface of the fourth ventricle (Fig. 8, D and E).
|
The effects of the transverse sectioning on SC-evoked PSPs were examined in left IBNs on the side opposite the right transverse section (Fig. 8C). After sectioning, inputs from the caudal and rostral SC on the right side were preserved with evidence of monosynaptic EPSPs (Fig. 8C, 7 and 8) and disynaptic IPSPs (Fig. 8C5), respectively. On the other hand, stimulation of the left rostral (Fig. 8C1) or caudal SC (Fig. 8C, 3 and 4) evoked no disynaptic IPSPs in this IBN and in all of the other 8 left IBNs examined in 3 cats. Therefore the inhibition from the left SC to left IBNs was mediated by right tectoreticular axons arising from left SC neurons. These findings also exclude the possibility that the inhibition from the right rostral SC to left IBNs is attributed to orthodromic commissural activation of, or the antidromic activation of commissural collaterals of, left tectoreticular neurons (dotted lines in Fig. 8A). In contrast, disynaptic inhibition from the contralateral (right) rostral SC remained after sectioning in 7 of the 8 left IBNs. Therefore the disynaptic inhibition from the contralateral (right) rostral SC to left IBNs was mediated by ipsilateral (left) tectoreticular axons arising from right rostral SC neurons.
Midline section between the 2 IBN regions
As the stimulation sites in the SC became progressively more caudal, monosynaptic excitation in the contralateral IBNs increased (Fig. 4C, 6–8), and disynaptic inhibition in ipsilateral IBNs (Fig. 4C, 1–4) and abducens motoneurons (Fig. 4B, 1–4) increased. These findings suggest that the inhibition in IBNs from the ipsilateral caudal SC might be mediated by contralateral IBNs. To explore this possibility, we examined the effect of sectioning the midline between the bilateral IBN regions on SC-evoked IPSPs in IBNs (Fig. 9). The midline section extended for 4–6 mm caudally from the middle of the abducens nucleus, and 
5.5–6.5 mm deep from the floor of the fourth ventricle in 3 cats (Fig. 9E). In these preparations, IBNs could not be identified by their antidromic activation from the contralateral abducens nucleus because of the midline section of commissural axons of IBNs. Therefore they were identified by their monosynaptic excitation from the contralateral SC (see METHODS) and their recording site, which was confirmed histologically after the experiments.
|
Interneurons for disynaptic inhibition from the ipsilateral caudal SC to IBNs
To confirm that the inhibition from the ipsilateral caudal SC to IBNs is mediated by contralateral IBNs, we analyzed PSPs in IBNs evoked by stimulation of the contralateral IBN region (Fig. 10). The IBN region was stimulated with an electrode array consisting of 4 electrodes arranged dorsoventrally (Fig. 10D). Stimulation of all of the 4 sites in and around the contralateral IBN region evoked hyperpolarizations (Fig. 10B, 1–4). These hyperpolarizations were reversed to depolarizations by Cl– injection (Fig. 10B, dotted traces) or by passing hyperpolarizing current into the cell, indicating that the hyperpolarizations were IPSPs (Eccles 1964). The shortest latencies of IPSPs were 0.9 ms at site 3. Amplitudes of IPSPs evoked from different sites at the same intensity were mapped in Fig. 10D and the effective stimulation sites were located in the IBN region as verified histologically after the experiment (Fig. 10, C and D). The latencies of the IPSPs ranged from 0.7 to 1.8 ms (mean ± SD, 0.9 ± 0.5 ms, n = 25). This finding confirmed that contralateral IBNs exerted monosynaptic inhibition on IBNs.
|
Interneurons for disynaptic inhibition from the rostral SC on both sides
To identify inhibitory interneurons mediating inhibition from the rostral SC, we examined the presence or absence of spatial facilitation of the disynaptic IPSPs evoked by stimulation of the rostral SC on both sides. Stimulation of the rostral parts of the ipsilateral (Fig. 11 Aa) and the contralateral SC (Fig. 11Ab) evoked IPSPs in the same IBN, respectively. Simultaneous stimulation of the ipsilateral and contralateral SCs evoked IPSPs (Fig. 11Ac), which were much larger than the algebraic sum of individual IPSPs (dashed line in Fig. 11Ac). Such spatial facilitation was observed in all of the 9 IBNs tested. The presence of the spatial facilitation indicated that tectoreticular neurons in the rostral part of the SC on both sides converge onto common last-order inhibitory interneurons terminating on an IBN. In 3 IBNs tested, similar spatial facilitation was seen in the preparations in which a midline section, such as that shown in Fig. 9, was made between the bilateral IBN regions. Taken together, these results indicated that tectoreticular axons arising from the rostral part of the SC on both sides converge onto common inhibitory interneurons other than IBNs that are located rostral to the IBN region and terminate on IBNs.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
). The present study has directly demonstrated that tectoreticular neurons in the SC exert monosynaptic excitation on contralateral IBNs.
Last-order premotor interneurons terminating on abducens motoneurons have been investigated by injecting HRP (Graybiel 1977a, b; Maciewicz et al. 1977) or WGA–HRP (Langer et al. 1986) into the abducens nucleus and mapping retrogradely labeled neurons in the brain stem. However, with this method several points of uncertainty remain for interpretation of the results: difficulty in localizing an injected tracer within the abducens nucleus, possibility of labeling passing fibers within and near the nucleus, difficulty in determining the exact number of neurons terminating in the nucleus, and incapability in determining whether they terminate on abducens motoneurons or internuclear neurons in the abducens nucleus. To overcome some of these methodological problems, a transneuronal-labeling method (Porter et al. 1985) was used for identifying the last-order interneurons terminating on abducens motoneurons, although the sensitivity of this staining method was low (Alstermark and Kümmel 1986; Harrison et al. 1986). When WGA–HRP was first introduced as a retrograde transneuronal tracer, it was suggested that this method could label only inhibitory interneurons such as inhibitory burst neurons and inhibitory vestibular neurons transneuronally (Porter et al. 1985). However, Alstermark and Kümmel (1990) suggested the possibility that both excitatory and inhibitory last-order interneurons could be transneuronally labeled in the spinal cord. By improving the sensitivity of this staining method (Sugiuchi et al. 1995), the present study succeeded in showing that this method could label both inhibitory and excitatory burst neurons and vestibular neurons. However, it was generally true that inhibitory neurons were labeled more heavily and abundantly in each preparation.
In the present study, transneuronally labeled neurons were located in the ipsilateral PPRF and the contralateral PPMRF. Labeled neurons in the PPRF were located from the level of the rostral end of the abducens nucleus to about 2.5 mm rostral, 0.3–2.0 mm lateral from the midline, and 0.5–2.3 mm deep from the floor of the fourth ventricle. Labeled neurons in the PPMRF were located in the region caudomedial to the caudal part of the abducens nucleus at 0.4–1.3 mm lateral from the midline and 0.5–2.5 mm deep from the floor of the fourth ventricle. Therefore the location of the present labeled neurons in the PPMRF is very consistent with the distribution of electrophysiologically identified IBNs in the cat (P 7.5–8.5 mm; Hikosaka and Kawakami 1977; P 7.0–9.0 mm; Yoshida et al. 1982), although the electrophysiological mapping was not so systematic. The information about the exact distribution of IBNs determined with this method helped efficient intracellular recording from IBNs and also effective stimulation of the IBN region.
There has been no previous systematic intracellular analysis of synaptic inputs from the SC to either EBNs or IBNs. The present study has shown that IBNs receive strong disynaptic inhibition from the caudal part of the ipsilateral SC. Stimulation of different sites in the SC evokes characteristic saccadic eye movements in awake cats (Guitton et al. 1980; McIlwain 1986) and monkeys (Robinson 1972; Sparks and Mays 1983; Stanford et al. 1996) and the spatial distribution of the effectiveness of stimulation in the SC for evoking EPSPs in abducens motoneurons is generally in accordance with the "motor map" obtained for horizontal saccadic components in awake animals (Guitton et al. 1980; Robinson 1972); as the distance from the rostral pole to the stimulation site in the SC increases, the amplitude of EPSPs evoked in abducens motoneurons also increases (Izawa et al. 1999). The same tendency was also observed in IBNs. At the onset of a saccade, SC neurons activate contralateral EBNs and IBNs, and these EBNs excite abducens motoneurons on the same side. Because IBNs give rise to axon terminals that ramify in the contralateral abducens nucleus, the PPRF and the PPMRF (Hikosaka et al. 1978; Strassman et al. 1986; Yoshida et al. 1982), they can provide inhibition not only to abducens motoneurons (Hikosaka and Kawakami 1977; Maeda et al. 1971a) but also to IBNs and probably EBNs on the opposite side. Therefore this antagonistic inhibition at supranuclear and motoneuronal levels ensures the suppression of saccades directed toward the side ipsilateral to active SC.
Another important finding in this study is that IBNs are inhibited by the rostral part of the SC on both sides. This inhibition is disynaptic and inhibitory interneurons are not IBNs because the midline section between the bilateral IBN regions did not affect the inhibition from the rostral SC on either side (Fig. 9D, 1 and 5), but eliminated inhibition from the ipsilateral caudal SC on IBNs (Fig. 9D, 3 and 4) and abducens motoneurons (Fig. 9C, 1–4). After transverse sectioning of tectoreticular fibers just rostral to the pause neuron (PN) region, the inhibition from the rostral SC on the nonsectioned side to IBNs on the sectioned side (Fig. 8B, 1 and 2) and to IBNs on the nonsectioned side (Fig. 8C, 1 and 2) would be eliminated. Therefore intervening interneurons for mediating this inhibition may be located at or caudal to the level of the PN region.
Pause neurons are a likely candidate responsible for mediating this inhibition. It has been reported that stimulation of the PN region induced monosynaptic inhibition in IBNs (Nakao et al. 1980). Stimulation of the PN region activates antidromically fixation neurons in the rostral SC (Gandhi and Keller 1997) and rostral SC stimulation activates PNs (Paré and Guitton 1994). The inhibition of IBNs caused by stimulation of the contralateral rostral SC is most likely mediated by inhibitory interneurons on the same side as the recorded IBNs because this inhibition remained after sectioning of the contralateral tectoreticular tract (Fig. 8C5) and disappeared after sectioning of the ipsilateral tectoreticular tract (Fig. 8B1). On the other hand, the inhibition of IBNs caused by stimulation of the ipsilateral rostral SC is most likely mediated by inhibitory interneurons opposite the recorded IBNs because this inhibition was eliminated by sectioning of the contralateral tectoreticular tract at the level just rostral to the PN region (Fig. 8C1) and remained after sectioning the ipsilateral tectoreticular tract (Fig. 8B5). This result also excluded the possibility that commissural neurons in the SC are responsible for the inhibition from the contralateral rostral SC. Specifically, 2 possibilities were eliminated. First, axon collaterals of tectoreticular neurons in the ipsilateral SC could not have been antidromically activated by stimulation of the contralateral SC and, second, ipsilateral SC neurons could not have been synaptically activated by stimulation of the commissural neurons in the contralateral SC (dashed presumed connections in the SCs in Fig. 8A). However, these conclusions cannot exclude the possibility that tri- or more synaptic inhibition might occur by commissural connections between the rostral SC on both sides. Axons of the inhibitory interneurons mediating inhibition from the ipsilateral rostral SC most likely cross the midline more rostrally than the IBN region because a midline section at the level of the IBN region did not eliminate inhibition from the ipsilateral rostral SC (Fig. 9D1). It is known that stem axons of most PNs cross the midline and project to the opposite PPRF and PPMRF (Ohgaki et al. 1987). Therefore if these PNs receive monosynaptic excitation from the rostral SC on the opposite side, this connection can explain the disynaptic inhibition in IBNs from the ipsilateral rostral SC.
In contrast, inhibitory interneurons that mediate the inhibition from the contralateral rostral SC to IBNs are more difficult to identify. Given that single PNs have bilateral projections to IBNs on both sides, stimulation of the rostral SC may evoke inhibition in IBNs on both sides. However, the presence of spatial facilitation between disynaptic inhibition from the rostral SC on both sides (Fig. 11A) indicated that the inhibition from the ipsi- and contralateral rostral SCs was mediated at least partly by common inhibitory interneurons other than IBNs. It was reported that some PNs project ipsilaterally (1 of 16 stained neurons in Ohgaki et al. 1987) or bilaterally (2 of 16 neurons in Ohgaki et al. 1987; some of 7 neurons in Strassman et al. 1987).
The axonal projection pattern of these ipsilaterally projecting PNs has not yet been described, but if they terminate on IBNs, they could mediate the inhibition from the contralateral SC to IBNs. In fact, the direct connection of ipsilateral PNs with IBNs was demonstrated using the postspike averaging method (Furuya and Markham 1982). Another possibility is PNs opposite IBNs. Some PNs have dendrites that spread into the medial reticular formation on both sides (Büttner-Ennever 1988; Ohgaki et al. 1987; Strassman et al. 1987). If these PNs receive monosynaptic excitation from the rostral SC on the same side, they could mediate the inhibition from the contralateral SC to IBNs. This connection may exist because single PNs receive convergent monosynaptic excitation from the rostral parts of the bilateral SCs (Y. Sugiuchi et al., unpublished observation). This finding could also account for the spatial facilitation between the IPSPs in IBNs evoked by stimulation of the bilateral rostral SCs (Fig. 11A). Figure 11B summarizes the most likely neural connections from the rostral and caudal parts of the SCs to IBNs on the basis of the present results.
The present results indicate that the rostral part of the SC on one side exerts inhibitory effects on bilateral IBNs, although the rostral SC inhibition was generally stronger for ipsilateral IBNs than for contralateral IBNs (Figs. 3 and 4). Paré and Guitton (1994) examined the effects of rostral SC stimulation on saccades in behaving cats and reported that stimulation of the rostral SC suppresses the generation of saccades in both directions. However, a detailed inspection of their data suggests that ipsilateral saccades are more strongly suppressed than contralateral saccades. This finding is consistent with the present result that the inhibitory effect of the rostral SC is stronger on ipsilateral IBNs. Their data do not necessarily indicate that the rostral SC has a stronger effect on ipsilateral EBNs and IBNs because stimulation of the rostral SC might have activated 2 inhibitory pathways as a result of stimulus current spread: one pathway arising from the rostral SC and the other from the more caudal SC. However, even after sectioning a midline to interrupt the inhibitory pathway from the caudal SC to IBNs, ipsilateral rostral SC stimulation usually evoked larger and slightly earlier disynaptic IPSPs in IBNs than contralateral rostral SC stimulation (compare Fig. 9D, 1 and 5), indicating that tectoreticular neurons in the rostral SC, probably fixation neurons, inhibit ipsilateral IBNs more strongly than contralateral IBNs by inhibitory interneurons.
Recent studies have shown that there are 2 types of suppression of saccades induced by electrical stimulation of the frontal eye field (FEF) in the monkey: suppression of ipsilateral saccades (Izawa et al. 2004a) and suppression of bilateral saccades (Izawa et al. 2004b). These suppressions occurred, not at a motoneuronal level, but at a premotor level, most likely the SC and/or the PPRF. Therefore the "fixation zone" in the rostral SC most likely receives input from the suppression area of the FEF. The suppression area for ipsilateral saccades may project to the ipsilateral rostral SC, which will suppress ipsilateral saccades by contralateral PNs. In contrast, the neural circuit for bilateral suppression is more difficult to explain. Given that single tectoreticular neurons in the rostral SC project to PNs on both sides, such neurons receiving input from the bilateral suppression area may suppress bilateral saccades. Further detailed study is required to determine the exact neural circuits for FEF suppression of saccades.
The present results have shown that differential projections from the rostral and caudal parts of the SC are directed to the pause neuron region in the PPRF and burst neuron region in the PPMRF, respectively, implying the differential functions of the rostral fixation zone and more caudal saccade zone of the SC. The rostral SC may suppress the initiation of saccades by increasing the level of tonic inhibitory input to IBNs and also EBNs, most likely by PNs. This interpretation is consistent with the previous findings that activation of the rostral SC interrupts saccades (Munoz and Wurtz 1993b; Paré and Guitton 1994) and inactivation of the rostral SC reduces the ability to suppress unwanted saccades (Munoz and Wurtz 1992, 1993b). Fixation neurons behaved as if their function was to actively maintain gaze on a target and prevent burst neurons from producing unwanted eye movements (Fuchs et al. 1985). Moreover, by ceasing to fire immediately before a saccade away from the fixation target, fixation neurons may partly contribute to triggering of the saccade.
However, recent studies have reported that the activity of neurons in the rostral SC is not always strictly related to maintaining fixation. Although fixation cells in the SC pause during ipsiversive saccades, many of them also increase their discharge rate during small contraversive saccades (Anderson et al. 1998; Munoz and Wurtz 1993a), suggesting that these neurons may excite EBNs to generate small saccades. Stimulation of the rostral SC not only interrupts saccades but can also alter their trajectory, suggesting a continuous representation of saccade size from the caudal to the rostral SC (Gandhi and Keller 1999). Furthermore, the rostral SC contains neurons that modulate their activity during pursuit eye movements (Krauzlis et al. 2002). Therefore the rostral SC appears to contain different groups of neurons. Further studies are required to determine whether "pure" fixation neurons and other movement-related neurons in the rostral SC have different connections with PNs, EBNs, and IBNs.
|
GRANTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: Y. Shinoda, Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan (E-mail: yshinoda.phy1{at}tmd.ac.jp)
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Alstermark B and Kümmel H. Transneuronal labelling of neurones projecting to forelimb motoneurones in cats performing different movements. Brain Res 376: 387–391, 1986.[CrossRef][Web of Science][Medline]
Alstermark B and Kümmel H. Transneuronal transport of wheat germ agglutinin conjugated horseradish peroxidase into last order spinal interneurones projecting to acromio-and spinodeltoideus motoneurones in the cat. 2. Differential labelling of interneurones depending on movement type. Exp Brain Res 80: 96–103, 1990.[Web of Science][Medline]
Anderson RW, Keller EL, Gandhi NJ, and Das S. Two-dimensional saccade-related population activity in superior colliculus in monkey. J Neurophysiol 80: 798–817, 1998.
Asanuma H and Arnold AP. Noxious effects of excessive currents used for intracortical microstimulation. Brain Res 96: 103–107, 1975.[CrossRef][Web of Science][Medline]
Baker R and Highstein SM. Physiological identification of interneurons and motoneurons in the abducens nucleus. Brain Res 91: 292–298, 1975.[CrossRef][Web of Science][Medline]
Basso MA and Wurtz RH. Modulation of neuronal activity in superior colliculus by changes in target probability. J Neurosci 18: 7519–7534, 1998.
Bender MB and Shanzer S. Oculomotor pathways defined by electrical stimulation and lesions in the brainstem of monkey. In: The Oculomotor System, edited by Bender MB. New York: Harper & Row, 1964, p. 81–140.
Büttner-Ennever JA and Büttner U. The reticular formation. In: Neuroanatomy of the Oculomotor System, edited by Büttner-Ennever JA. Amsterdam: Elsevier, 1988, p. 119–176.
Büttner-Ennever JA, Cohen B, Pause M, and Fries W. Raphe nucleus of the pons containing omnipause neurons of the oculomotor system in the monkey, and its homologue in man. J Comp Neurol 267: 307–321, 1988.[CrossRef][Web of Science][Medline]
Büttner-Ennever JA and Horn AK. Neuroanatomy of saccadic omnipause neurons in nucleus raphe interpositus. In: Contemporary Ocular Motor and Vestibular Research: A Tribute to David A. Robinson, edited by Fuchs AF, Brandt T, Büttner U, and Zee DS. New York: Georg Thieme Verlag, 1994, p. 488–495.
Chimoto S, Iwamoto Y, Shimazu H, and Yoshida K. Monosynaptic activation of medium-lead burst neurons from the superior colliculus in the alert cat. J Neurophysiol 75: 2658–2661, 1996.
Cohen B and Henn V. Unit activity in the pontine reticular formation associated with eye movements. Brain Res 46: 403–410, 1972.[CrossRef][Web of Science][Medline]
Cohen B and Komatsuzaki A. Eye movements induced by stimulation of the pontine reticular formation. Exp Neurol 36: 101–117, 1972.[CrossRef][Web of Science][Medline]
Cohen B, Komatsuzaki A, and Bender MB. Electro-oculographic syndrome in monkeys after pontine reticular formation lesions. Arch Neurol 18: 78–92, 1968.
Curthoys IS, Nakao S, and Markham CH. Cat medial pontine reticular neurons related to vestibular nystagmus: firing pattern, location and projection. Brain Res 222: 75–94, 1981.[CrossRef][Web of Science][Medline]
Eccles JC. Physiology of Synapses. Berlin: Springer-Verlag, 1964.
Evinger C, Kaneko CRS, and Fuchs AF. Activity of omnipause neurons in alert cats during saccadic eye movements and visual stimuli. J Neurophysiol 47: 827–844, 1982.
Evinger C, Kaneko CRS, Johanson TW, and Fuchs AF. Omnipauser cells in the cat. In: Control of Gaze by Brain Stem Neurons. Developments in Neuroscience, edited by Baker R and Berthoz A. New York: Elsevier/North-Holland Biomedical Press, 1977, vol. 1, p. 337–340.
Fuchs AF, Kaneko CR, and Scudder CA. Brainstem control of saccadic eye movements. Ann Rev Neurosci 8: 307–337, 1985.[CrossRef][Web of Science][Medline]
Furuya N and Markham CH. Direct inhibitory synaptic linkage of pause neurons with burst inhibitory neurons. Brain Res 245: 139–143, 1982.[CrossRef][Web of Science][Medline]
Gandhi NJ and Keller EL. Spatial distribution and discharge characteristics of superior colliculus neurons antidromically activated from the omnipause region in monkey. J Neurophysiol 78: 2221–2225, 1997.
Gandhi NJ and Keller EL. Comparison of saccades perturbed by stimulation of the rostral superior colliculus, the caudal superior colliculus, and the omnipause neuron region. J Neurophysiol 82: 3236–3253, 1999.
Gerrits NM, Voogd J, and Magras N. Vestibular afferents of the inferior olive and the vestibulo-olivo-cerebellar climbing fiber pathway to the flocculus in the cat. Brain Res 332: 325–336, 1985.[CrossRef][Web of Science][Medline]
Goldberg ME and Wurtz RH. Activity of superior colliculus in behaving monkey. I. Visual receptive fields of single neurons. Neurology 21: 542–559, 1972.
Grantyn AA and Grantyn R. Synaptic actions of tectofugal pathways on abducens motoneurons in the cat. Brain Res 105: 269–285, 1976.[CrossRef][Web of Science][Medline]
Grantyn AA and Grantyn R. Axonal patterns and site of termination of cat superior colliculus neurons projecting in the tecto-bulbo-spinal tract. Exp Brain Res 46: 243–256, 1982.[Web of Science][Medline]
Graybiel AM. Direct and indirect preoculomotor pathways of the brain stem: an autoradiographic study of the pontine reticular formation in the cat. J Comp Neurol 175: 37–78, 1977a.[CrossRef][Web of Science][Medline]
Graybiel AM. Organization of oculomotor pathways in the cat and rhesus monkey. In: Control of Gaze by Brain Stem Neurons. Developments in Neuroscience, edited by Baker R and Berthoz A. New York: Elsevier/North-Holland Biomedical Press, 1977b, p. 79–88.
Guitton D. Control of saccadic eye and gaze movements by the superior colliculus and basal ganglia. In: Eye Movements, edited by Carpenter RHS. Boca Raton, FL: CRC Press, 1991, p. 244–276.
Guitton D, Crommelinck M, and Roucoux A. Stimulation of the superior colliculus in the alert cat. I. Eye movements and neck EMG activity evoked when the head is restrained. Exp Brain Res 39: 63–73, 1980.[Web of Science][Medline]
Harrison PJ, Jankowska E, and Zytnicki D. Lamina VIII interneurones interposed in crossed reflex pathway in the cat. J Physiol 371: 147–166, 1986.
Harting JK. Descending pathways from the superior colliculus: an autoradiographic analysis in the rhesus monkey (Macaca mulatta). J Comp Neurol 173: 583–612, 1977.[CrossRef][Web of Science][Medline]
Henn V, Lang W, Hepp K, and Reisine H.Experimental gaze palsies in monkeys and their relation to human pathology. Brain 107: 619–363, 1984.
Hikosaka O, Igusa Y, and Imai H. Inhibitory connections of nystagmus related reticular burst neurons with neurons in the abducens, prepositus hypoglossi and vestibular nuclei in the cat. Exp Brain Res 39: 301–311, 1980.[Web of Science][Medline]
Hikosaka O, Igusa Y, Nakao S, and Shimazu H. Direct inhibitory synaptic linkage of pontomedullary reticular burst neurons with abducens motoneurons in the cat. Exp Brain Res 33: 337–352, 1978.[Web of Science][Medline]
Hikosaka O and Kawakami T. Inhibitory reticular neurons related to the quick phase of vestibular nystagmus—their location and projection. Exp Brain Res 27: 377–396, 1977.[Web of Science][Medline]
Izawa Y, Sugiuchi Y, and Shinoda Y. Neural organization from the superior colliculus to motoneurons in the horizontal oculomotor system of the cat. J Neurophysiol 81: 2597–2611, 1999.
Izawa Y, Suzuki H, and Shinoda Y. Suppression of visually- and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. I. Suppression of ipsilateral saccades. J Neurophysiol 92: 2248–2260, 2004a.
Izawa Y, Suzuki H, and Shinoda Y. Suppression of visually- and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. II. Suppression of bilateral saccades. J Neurophysiol 92: 2261–2273, 2004b.
Jankowska E, Padel Y, and Tanaka R. The mode of activation of pyramidal tract cells by intracortical stimuli. J Physiology 249: 617–636, 1975.
Kawamura K and Hashikawa T. Cell bodies of origin of reticular projections from the superior colliculus in the cat: an experimental study with the use of horseradish peroxidase as a tracer. J Comp Neurol 182: 1–16, 1978.[CrossRef][Web of Science][Medline]
Keller EL. Participation of medial pontine reticular formation in eye movement generation in monkey. J Neurophysiol 37: 316–332, 1974.
Krauzlis RJ, Basso MA, and Wurtz RH. Discharge properties of neurons in the rostral superior colliculus of the monkey during smooth-pursuit eye movements. J Neurophysiol 84: 876–891, 2002.
Langer T and Kaneko CRS. Brainstem afferents to omnipause region in the cat: a horseradish peroxidase study. J Comp Neurol 230: 444–458, 1984.[CrossRef][Web of Science][Medline]
Langer T, Kaneko CRS, Scudder CA, and Fuchs AF. Afferents to the abducens nucleus in the monkey and cat. J Comp Neurol 245: 379–400, 1986.[CrossRef][Web of Science][Medline]
Langer TP and Kaneko CRS. Brainstem afferents to the oculomotor omnipause neurons in monkey. J Comp Neurol 295: 413–427, 1990.[CrossRef][Web of Science][Medline]
Luschei E and Fuchs AF. Activity of brain stem neurons during eye movements of alert monkeys. J Neurophysiol 35: 445–461, 1972.
Maciewicz RJ, Kaneko CR, Highstein SM, and Eagen K. Vestibular and medullary brain stem afferents to the abducens nucleus in the cat. Brain Res 123: 229–240, 1977.[CrossRef][Web of Science][Medline]
Maeda M, Shimazu H, and Shinoda Y. Inhibitory postsynaptic potentials in the abducens motoneurons associated with the quick relaxation phase of vestibular nystagmus. Brain Res 26: 420–424, 1971a.[CrossRef][Web of Science][Medline]
Maeda M, Shimazu H, and Shinoda Y. Rhythmic activities of secondary vestibular efferent fibers recorded within the abducens nucleus during vestibular nystagmus. Brain Res 34: 361–365, 1971b.[CrossRef][Web of Science][Medline]
McIlwain JT. Effects of eye position on saccades evoked electrically from superior colliculus of alert cats. J Neurophysiol 55: 97–112, 1986.
Moschovakis AK and Karabelas AB. Observations on the somatodendritic morphology and axonal trajectory of intracellularly HRP-labeled efferent neurons located in the deeper layers of the superior colliculus of the cat. J Comp Neurol 239: 276–308, 1985.[CrossRef][Web of Science][Medline]
Moschovakis AK, Kitama T, Dalezios Y, Petit J, Brandi AM, and Grantyn AA. An anatomical substrate for the spatiotemporal transformation. J Neurosci 18: 10219–10229, 1998.
Munoz DP and Guitton D. Fixation and orientation control by the tecto-reticulo-spinal system in the cat whose head is unrestrained. Rev Neurol (Paris) 145: 567–579, 1989.[Medline]
Munoz DP and Guitton D. Control of orienting gaze shifts by the tectoreticulospinal system in the head-free cat. II. Sustained discharges during motor preparation and fixation. J Neurophysiol 66: 1624–1641, 1991.
Munoz DP, Guitton D, and Pelisson D. Control of orienting gaze shifts by the tectoreticulospinal system in the head-free cat. III. Spatiotemporal characteristics of phasic motor discharges. J Neurophysiol 66: 1642–1666, 1991.
Munoz DP and Istvan PJ. Lateral inhibitory interactions in the intermediate layers of the monkey superior colliculus. J Neurophysiol 79: 1193–1209, 1998.
Munoz DP and Wurtz RH. Role of the rostral superior colliculus in active visual fixation and execution of express saccades. J Neurophysiol 67: 1000–1002, 1992.
Munoz DP and Wurtz RH. Fixation cells in monkey superior colliculus. I. Characteristics of cell discharge. J Neurophysiol 70: 559–575, 1993a.
Munoz DP and Wurtz RH. Fixation cells in monkey superior colliculus. II. Reversible activation and deactivation. J Neurophysiol 70: 576–589, 1993b.
Munoz DP and Wurtz RH. Saccade-related activity in monkey superior colliculus. I. Characteristics of burst and buildup cells. J Neurophysiol 73: 2313–2333, 1995a.
Munoz DP and Wurtz RH. Saccade-related activity in monkey superior colliculus. II. Spread of activity during saccades. J Neurophysiol 73: 2334–2348, 1995b.
Nakao S, Curthoys IS, and Markham CH. Direct inhibitory projection of pause neurons to nystagmus-related pontomedullary reticular burst neurons in the cat. Exp Brain Res 40: 283–293, 1980.[Web of Science][Medline]
Ohgaki T, Curthoys IS, and Markham CH. Anatomy of physiologically identified eye-movement-related pause neurons in the cat: pontomedullary region. J Comp Neurol 266: 56–72, 1987.[CrossRef][Web of Science][Medline]
Ohgaki T, MarkhamCH, Schneider JS, and Curthoys IS. Anatomical evidence of the projection of pontine omnipause neurons to midbrain regions controlling vertical eye movements. J Comp Neurol 289: 610–625, 1989.[CrossRef][Web of Science][Medline]
Olivier E, Grantyn AA, Chat M, and Berthoz A. The control of slow orienting eye movements by tectoreticulospinal neurons in the cat: behavior, discharge patterns and underlying connections. Exp Brain Res 93: 435–449, 1993.[Web of Science][Medline]
Paré M, Crommelinck M, and Guitton D. Gaze shift evoked by stimulation of the superior colliculus in the head-free cat conform to the motor map but also depend on stimulus strength and fixation activity. Exp Brain Res 101: 123–139, 1994.[Web of Science][Medline]
Paré M and Guitton D. The fixation area of the cat superior colliculus: effects of electrical stimulation and direct connection with brainstem omnipause neurons. Exp Brain Res 101: 109–122, 1994.[Web of Science][Medline]
Peck CK. Visual responses of neurons in cat superior colliculus in relation to fixation of targets. J Physiol 414: 301–315, 1989.
Porter JD, Guthrie BL, and Sparks DL. Selective retrograde transneuronal transport of wheat germ agglutinin-conjugated horseradish peroxidase in the oculomotor system. Exp Brain Res 57: 411–416, 1985.[Web of Science][Medline]
Precht W, Schwindt PC, and Magherini PC. Tectal influences on cat ocular motoneurons. Brain Res 82: 27–40, 1974.[CrossRef][Web of Science][Medline]
Raybourn MS and Keller EL. Colliculoreticular organization in primate oculomotor system. J Neurophysiol 40: 861–878, 1977.
Robinson DA. Eye movements evoked by collicular stimulation in the alert monkey. Vision Res 12: 1795–1808, 1972.[CrossRef][Web of Science][Medline]
Schiller PH and Körner F. Discharge characteristics of single units in superior colliculus of the alert rhesus monkey. J Neurophysiol 34: 920–936, 1971.
Scudder CA, Moschovakis AK, Karabelas AB, and Highstein SM. Anatomy and physiology of saccadic long-lead burst neurons recorded in the alert squirrel monkey. I. Descending projections from the mesencephalon. J Neurophysiol 76: 332–352, 1996.
Shinoda Y, Arnold AP, and Asanuma H. Spinal branching of corticospinal axons in the cat. Exp Brain Res 26: 215–234, 1976.[Web of Science][Medline]
Shinoda Y, Ohgaki T, Sugiuchi Y, and Futami T. Morphology of single medial vestibulospinal tract axons in the upper cervical spinal cord of the cat. J Comp Neurol 316: 151–172, 1992.[CrossRef][Web of Science][Medline]
Shinoda Y, Sugiuchi Y, and Futami T. Excitatory inputs to cerebellar dentate nucleus neurons from the cerebral cortex in the cat. Exp Brain Res 67: 299–315, 1987.[Web of Science][Medline]
Shinoda Y, Yamaguchi T, and Futami T. Multiple axon collaterals of single corticospinal axons in the cat spinal cord. J Neurophysiol 55: 425–448, 1986.
Shinoda Y, Yokota J, and Futami T. Divergent projection of individual corticospinal axons to motoneurons of multiple muscles in the monkey. Neurosci Lett 23: 7–12, 1981.[CrossRef][Web of Science][Medline]
Shinoda Y, Yokota J, and Futami T. Morphology of physiologically identified rubrospinal axons in the spinal cord of the cat. Brain Res 242: 321–325, 1982.[CrossRef][Web of Science][Medline]
Shinoda Y and Yoshida K. Dynamic characteristics of responses to horizontal head angular acceleration in vestibuloocular pathway in the cat. J Neurophysiol 37: 653–673, 1974.
Sparks DL and Hartwich-Young R. The deep layers of the superior colliculus. In: The Neurobiology of Saccadic Eye Movements, edited by Wurtz RH and Goldberg ME. Amsterdam: Elsevier, 1989, p. 213–255.
Sparks DL and Mays LE. Spatial localization of saccade targets. I. Compensation for stimulation-induced perturbation in eye position. J Neurophysiol 49: 64–74, 1983.
Stanford TR, Freedman EG, and Sparks DL. Site and parameters of microstimulation: evidence of independent effects on the properties of saccades evoked from the primate superior colliculus. J Neurophysiol 76: 3360–3380, 1996.
Strassman A, Evinger C, McCrea RG, Baker RG, and Highstein SM. Anatomy and physiology of intracellularly labeled omnipause neurons in the cat and squirrel monkey. Exp Brain Res 67: 436–440, 1987.[Web of Science][Medline]
Strassman A, Highstein SM, and McCrea RA. Anatomy and physiology of saccadic burst neurons in the alert squirrel monkey. II. Inhibitory burst neurons. J Comp Neurol 249: 358–380, 1986.[CrossRef][Web of Science][Medline]
Sugiuchi Y, Izawa Y, and Shinoda Y. Trisynaptic inhibition from the contralateral vertical semicircular canal nerves to neck motoneurons mediated by spinal commissural neurons. J Neurophysiol 73: 1973–1987, 1995.
Wurtz RH and Goldberg ME. Activity of superior colliculus in behaving monkey. III. Cells discharging before eye movements. J Neurophysiol 35: 575–586, 1972.
Yoshida K, McCrea R, Berthoz A, and Vidal PP. Morphological and physiological characteristics of inhibitory burst neurons controlling horizontal rapid eye movements in the alert cat. J Neurophysiol 48: 761–784, 1982.
This article has been cited by other articles:
|
|
 |
|
  Y. Iwamoto, H. Kaneko, K. Yoshida, and H. Shimazu Role of Glycinergic Inhibition in Shaping Activity of Saccadic Burst Neurons J Neurophysiol, June 1, 2009; 101(6): 3063 - 3074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ikeda and O. Hikosaka Positive and Negative Modulation of Motor Response in Primate Superior Colliculus by Reward Expectation J Neurophysiol, December 1, 2007; 98(6): 3163 - 3170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takahashi, Y. Sugiuchi, and Y. Shinoda Commissural Mirror-Symmetric Excitation and Reciprocal Inhibition Between the Two Superior Colliculi and Their Roles in Vertical and Horizontal Eye Movements J Neurophysiol, November 1, 2007; 98(5): 2664 - 2682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Prsa and H. L. Galiana Visual-Vestibular Interaction Hypothesis for the Control of Orienting Gaze Shifts by Brain Stem Omnipause Neurons J Neurophysiol, February 1, 2007; 97(2): 1149 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Condy, N. Wattiez, S. Rivaud-Pechoux, L. Tremblay, and B. Gaymard Antisaccade Deficit after Inactivation of the Principal Sulcus in Monkeys Cereb Cortex, January 1, 2007; 17(1): 221 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takahashi, Y. Sugiuchi, Y. Izawa, and Y. Shinoda Commissural Excitation and Inhibition by the Superior Colliculus in Tectoreticular Neurons Projecting to Omnipause Neuron and Inhibitory Burst Neuron Regions J Neurophysiol, September 1, 2005; 94(3): 1707 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Waitzman So Much to See, So Little Time: How the Superior Colliculus (SC) Suppresses Unwanted Saccades. Focus on "Physiological Characterization of Synaptic Inputs to Inhibitory Burst Neurons From the Rostral and Caudal Superior Colliculus" J Neurophysiol, February 1, 2005; 93(2): 641 - 642. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
