Projection from the accommodation-related area in the superior colliculus of the cat

THE JOURNAL OF COMPARATIVE NEUROTJOGY 367~465476 (1996)

Projection From the Accommodation-Related Area

in the Superior Colliculus of the Cat

AKIHIKO SAT0 AND KENJI OHTSUKA Department of Ophthalmology, School of Medicine, Sapporo Medical University,

Sapporo, Hokkaido 060, Japan

ABSTRACT Our previous study has indicated that accommodative responses can be evoked with weak

currents applied to a circumscribed area of the superior colliculus in the cat. We investigated efferent projections from this area with biocytin in the present study. The accommodation area in the superior colliculus was identified by systematic microstimulation in each of five anesthetized cats. Accommodative responses were detected by an infrared optometer. After mapping the superior colliculus, biocytin was injected through a glass micropipette into the accommodation area, where accommodative responses were elicited with low-intensity microstimulation. In addition, accommodative responses to stimulation of the superior colliculus were compared before and after an injection of muscimol, an agonist of inhibitory neurotrans- mitter, into the pretectum.

Following the injection of biocytin, in the ascending projections, labeled terminals were seen mainly in the caudal portion of the nucleus of the optic tract, the nucleus of the poslerior commissure, the posterior pretectal nucleus, the olivary pretectal nucleus, the mesencephalic reticular formation at the level of the oculomotor nucleus, and the lateral posterior nucleus of the thalamus on the ipsilateral side. Less dense terminals were seen in the anterior pretectal nucleus, the zona incerta, and the centromedian nucleus of the thalamus. In the descending projections, labeled terminals were observed mainly in the paramedian pontine reticular formation, the nucleus raphe interpositus, and the dorsomedial portion of the nucleus reticularis tegmenti pontis on the contralateral side. Less dense terminals were also seen in the nucleus of the brachium of the inferior colliculus, the cuneiform nucleus, the medial part of the paralemniscal tegmental field, and the dorsolateral division of the pontine nuclei on the ipsilateral side. Following the injection of muscimol into the pretectum, including the nucleus of the optic tract, the posterior pretectal nucleus, and the nucleus of the posterior commissure, accommodative responses evoked by microstimulation of the superior colliculus were reduced to 3 3 4 5 % of the value before the injections.

These findings suggest that the accommodation area in the superior colliculus projects to the oculomotor nucleus through the ipsilateral pretectal area, especially the nucleus of the optic tract, the nucleus of posterior commissure, and the posterior pretectal nucleus, and also projects to the pupilloconstriction area (the olivary pretectal nucleus), the vergence-related area (the mesencephalic reticular formation), and the active visual fixation-related area (the nucleus raphe interpositus). I; 1996 Wile?-Liss. Inc.

Indexing terms: hiocytin study, prcteetum, ocular near response, vergence, fixation

Previous studies have suggested that the lateral supraspl- vian (LS) area, the cortical area surrounding the middle suprasylvian sulcus (Mss) of the cat, is related to the control of lens accommodation (Bando et al., 1981, 1984b; Sawa et al., 1992). The LS area receives visual inputs. Some neurons in this area respond l o changes in ocular disparity and

visual cues for accommodation (Toyama and Kozasa, 1982;

Toyama et al.: 1986a>b). Some LS neurons also exhibit burst discharges preceding the onset of spontaneous accommodation (Bando et al., 1984b). It is likely that these

-__- Accepted November 10,1995. Address reprint requests to Kenji Ohtsuka, M.D., Ph.D., Department of

Ophthalmology, School of Medicine, Sapporo Medical IJniversity, S-1, W-l 6, target and to motion in depth, which are important Chuo-ku, Sapporo 060. Japan.

O 1996 WILEY-LISS, INC.

466 A. SAT0 AND K. OHTSUK.4

neurons have an important role in the control of accommodation, Microstimulation of the LS area evokes accommodative responses (Bando et al., 1981; Sawa et al., 1992). We conducted systematic microstimulation of the LS area in the cat and found that low-threshold areas for evoking lens accommodation were located in the lower parts of the medial banks of the Mss from A1 to A4 and at A8 in the stereotaxic coordinates (Sawa et al., 1992). The latency of accommodative responses evoked by stimulation of the caudal area (Al-A4) was shorter than that of accommodative responses evoked by stimulation of the rostral area (A8). It is probable that the caudal accommodation area provides output motor signals for the subcortical system to control lens accommodation. The LS area projects to many areas, such as other cortical areas, the thalamus, the pulvinar, the striatum, the pretectum, the superior colliculus (SC)! and the pontine nuclei (Kawamura et al., 1974; Updyke, 1981; Segal and Beckstead, 1984; Norita et al., 1991). Bando et al. (1984b3 reported that about 70% of accommodation relay to neurons in LS were antidromically activated by stimulation via electrodes placed in the pretectum and/or the superior colliculus, with average latencies of 2.4-2.5 ms.

We reported that following injections of wheatgerm agglutinin conjugated with horseradish peroxidase into the low-threshold area in the caudal accommodation area of the cat, dense labeling of axon terminals was observed in the rostral portion of the ipsilateral SC, which corresponded to the representation of the central visual field; labeled terminals were not clearly evident in the nucleus of the optic tract (NOT; Maekawa and Ohtsuka, 1993). Accommodative responses evoked by microstimulation of the LS were almost abolished after injection of muscimol (agonist to gamma-aminobutyric acid, or GABA) into the SC (Ohtsuka and Sato, 1996). In addition, accommodative responses were evoked by low-current stimuli ( < 20 FAj of a circumscribed area of the SC: corresponding to the terminal portion from the cortical accommodation area (Sawa and Ohtsuka, 1994). These findings suggest that the SC has an important role in the control of accommodation in the brainstem.

APN

BIC BP BSC CM CN D HB IC IN INC LGN LL LPi LPI LPm MD MGN ML MLP motV MPN MRF NOT NPC

nc anterior pretectal nucleus brachium conjunctivum hrachium of the inferior colliculus brachium pontis hrachiurn o f the superior colliculus centrornedian nucleus cuneiform nucleus Nucleus of Darkschewikch habenular nucleus inferior colliculus interpeduncular nucleus Interstitial nucleus of Cajal lateral geniculate nucleus lateral leminiscus interjacent division of lateral posteiior nucleus lateral division of lateral posterior nucleus medial division of lateral posterior nucleus mediodorsal nucleus medial geniculate nucleus medial lemniscus medial longitudinal fasciculus motor trigeminal nucleus medial pretectal nucleus mesencephalic reticular formation nucleus of the optic tract nucleus of the posterior commissure

In this study, we injected biocytin into the low-threshold area for evoking accommodative responses in the SC of the cat and studied the efferent connections of the accommodation area in the SC. In addition, accommodative responses to stimulation of the SC were compared before and after an injection of muscimol into the the pretectum. The pretectum receives inputs from the SC (Benevento and Fallon, 1975; Graham, 1977; Harting et al.. 1980; Kubota et al., 1989) and is thought to be related to the control of accommodation (Hultborn et al., 1978a; Konno and Oht- suka, 1995). If the accommodation area in the SC projects to the oculomotor nucleus through the pretectum, accommodative responses evoked by microstimulation of the SC will be reduced after the injection of muscimol into the pretectum.

MATERIALS AND METHODS The general paradigm of the present experiments was to

determine the efferent connections of the accommodation area in the SC by injecting biocytin through glass micropipettes into a region immediately after the region was mapped electrophysiologically. This study was conducted in five cats weighing 2.5-3.5 kg. In addition, accommodative responses to stimulation of the SC were compared before and after inject,ion of muscimol into the projection area (the pretectal area) from the SC to determine whether or not the projection from the SC is related to the control of accommodation. Three cats weighing 2.5-3.0 kg were used for this experiment.

Surgical preparations Each cat was deeply anesthetized with 2-4% halothane.

After the trachea and the saphenous vein were cannulated, halothane anesthesia was substituted with ketamine hydrochloride (initial dose, 25 mg/kg, i.m.1 and a-chloralose (25 mgikg, i.v.). For accurate measurement of the dioptric change of the lens, each animal was immobilized with pancuronium bromide (initial dose, 0.1 mg/kg, i.v.) and artificially ventilated. Pancuronium bromide (0.05 mgikg,

Abbreviations

NRM NRTP OPN nVIl OMN P PAG PB PC PF PL PON PPN PPRF PT RIP RN sc SG SN SO Vprinc

ZI 11-VII

VSP

nucleus raphc magnus nucleus reticularis tegmenti pontis olivary pretectal nucleus facial nerve oculomotor nucleus pyramidal tract periaqueductal gray matter parabigeminal nucleus pedunculus cerebri parafascicular nucleus pulvinar pontine nuclei posterior pretectal nucleus paramedian pontine reticular formation pretectum nucleus raphe interpositus red nucleus superior colliculus suprageniculatc nucleus substantia nigra pars rel.icu1at.a superior olivary complex principal trigeminal nucleus spinal trigeminal complex zona incerta specific layers of superior colliculus

ACCOMMODATION SYSTEM IN THE RRAINSTEM 467

i.v.1 was administered every 40 minutes. The animal was attached to a stereotaxic head-holder frame. A small crani- otomy was made in the parietal skull for later insertions of microelectrodes and glass micropipettes into the SC and the pretectal area. All incisions and pressure points were infiltrated with 2% lidocaine hydrochloride. Rectal temperature was maintained a t 38°C by a feedback-controlled heating pad. During the experiment, supplemental doses of ketamine hydrochloride (15 mgikg, i.m.1 and a-chloralose (10 mgikg, i.v.1 were administered every 30 minutes. The right pupil was dilated for accurate measurement of accommodation with 5% L-phenylephrine hydrochloride, a drug that produces no measurable effect on the accommodative response (Ripps et al., 1962). All experimental protocols were approved by the Sapporo Medical University Animal Care and Use Committee and complied with the National Institutes of Health guidelines for animal care and use.

Mapping and recording procedures The procedures employed to record accommodation and

mapping of the SC in the cat have been described elsewhere (Sawa and Ohtsuka, 1994). Accommodative responses of the right eye were continuously recorded with an infrared optometer (Nidek, AR-1100). This system was basically analogous to the system developed by Cornsweet and Crane (1970). For accurate measurement, the ocular alignment of the right eye was continuously monitored with an infrared TV monitor mounted in the optometer. This system has a resolution of 0.01 diopter. Lens accommodation and trigger pulses for stimulation were recorded on magnetic tapes for subsequent computer analysis by using a PCM data re- corder (TEAC, RD-111T). The data recorded on magnetic tapes were digitized by a computer (Macintosh IIci) at a sampling rate of 200 Hz for later analysis.

Tungsten microelectrodes insulated with Isonel 31 (Niss- hoku) were used for electrical microstimulation. The electrodes were introduced stereotaxically into the SC along the vertical axis with a micromanipulator. The microelectrode was used initially as an electrode for recording neuronal discharge to identify the surface of the SC. When the tip of the microelectrode reached the surface of the SC, the microelectrode was connected to a stimulator. Our previous study (Sawa and Ohtsuka, 1994) demonstrated that the lowest threshold area for evoking accommodation was located about 1-1.5 mm below the surface of the SC. The variables of the stimulation were negative pulses of 0.2-ms duration at 250 pulses per second for 0.5 seconds. Approxi- mately 5-10 electrode penetrations (intervals of 0.5-1.0 mm) were made to determine the low-threshold area for evoking accommodation in the SC in each cat. Routinely, the maximum current (60 FA) was first applied to determine if lens accommodation could be evoked. If no accommodative responses were evoked, the electrode was advanced 500 pm. If accommodative responses were evoked, the stimulus intensity was lowered to the threshold that was defined as the intensity that elicited 7-8 accommodative responses of 0.03 diopter or larger from 10 stimulations.

Biocytin injection After mapping the thresholds for evoking accommodative

responses was completed, a track where accommodative responses were elicited with the lowest threshold in the SC was selected in each cat. Our previous study (Sawa and Ohtsuka, 1994) showed that accommodative responses can be elicited with low-current stimuli weaker than 20 FA. The

microelectrode was replaced with a glass microelectrode pulled from 1-mm glass tubing, bevelled to a tip diameter of 70-90 pm, which was filled with a 5% solution of biocytin (Sigma) in 0.05 M Tris-HC1 buffer (pH 7.6) and 0.2 M KCl (Fig. 1). Prior tu the injection, we confirmed that accommodation was evoked by microstimulation of the injection site with low current < 20 pA) by using the glass micropipette (Fig. I). In five cats, 0.2-0.4 p1 of the solution was injected under pressure, over a 10-15-minute period by using a microdriver of a 10-p1 microsyringe connected to the micropipette.

Muscimol injection In three cats, muscimol was injected into the pretectum,

which receives many projections from the SC (Benevento and Fallon, 1975; Graham, 1977; Harting et al., 1980; Kubota et al., 1989) and is related to the control of accommodation (Hultborn et al., 1978a; Konno and Oht- suka, 1995). Accommodative responses to stimulation of the SC were compared before and after an injection of muscimol into the ipsilateral pretectum. The pretectum, especially the nucleus of the optic tract (NOT), contains substantial numbers of GABAergic terminals (Penny et al., 1984; Giolli et al., 1985). Therefore, neuronal activity in the pretectum is expected to be inhibited after the injection of muscimol. If the accommodation area in the SC projects to the oculomotor nucleus through the pretectum, accommodation evoked by microstimulation of the SC will be reduced after muscimol administration. Tungsten microelectrodes for microstimulation were introduced stereotaxically into the accommodation area in the SC at an angle of 10" from the vertical axis in a sagittal plane. Glass micropipettes, which were filled with 1 ~ g i pl saline solution of muscimol (Sigma), were introduced stereotaxically into the pretectum along the vert,ical axis on the same side as the tungsten microelectrode. The solution was stained with fast green for later identification of the injection sites. Single or multiple injections (2-3) of muscimol, spaced 0.25-0.5 mm apart, were made mainly into the NOT, where accommodative responses are evoked with low-current stimuli ( < 20 FA; Konno and Ohtsuka, 1995). The total amount of muscimol injected ranged from 0.5 to 1.0 ~ 1 . In the control animal, 0.2-0.5 pl of saline was injected into the pretectum to indicate no effects.

Histological processing and data analysis Following 14-24 hours

of survival, the animals were deeply anesthetized with pentobarbital sodium and perfused transcardially. Two liters of physiological saline were introduced, followed by 2 liters of fixative solution containing 1% paraformaldehyde and 1% glutaraldehyde in 0.1 M phosphate buffer (pH 7.4). Following perfusion, the brains were exposed and blocked in the stereotaxic plane, placed in 0.1 M phosphate buffer containing 20% sucrose, and kept in a refrigerator over- night. The following day, brains were sectioned into 40- 60-pm serial coronal sections on a freezing microtome and collected in compartmentalized trays. The sections of the brain were rinsed with 0.1 M phosphate buffer (pH 7.4) containing 0.3% Triton X and preincubated with horseradish peroxidase avidin D (Vector, 1500) dissolved in 0.1 M phosphate buffer with 0.3% Triton X at room temperature for 3 hours. Then, the sections were treated with 0.05% diaminobenzidine (DAB) in 0.1 M phosphate buffer with nickelicobalt acetate. The sections were incubated with 3%

For the biocytin experiments.

465 A. SAT0 AND K. OHTSUKA

Accommodation

10.2D

0 2 4 Sec. \ Rostra1 \

Fig. 1. Schematic diagram shows the method for biocytin injections into the physiologically idcntified accommodation area of thc rostral SC by using a glass microelectrode and accommodative responses evoked by microstimulation of the injection site in a cat (inset), and drawings of serial coronal sections through the rostral SC in the stereotaxic plane

show the distributions of the injection sites in five cats. The solid black regions rcprcscnt thc extent of the most probable effective injection site. In each case, hiocytin was injected into the region where accommodative responses were evoked by microstimulation with weak currents ( c 20 wA). Scale bar = 2 mm.

H202 added to DAB solution (300 p1 of 3% HzOz to 100 ml DAB solution) for 5-20 minutes. Finally, the sections were rinsed in 0.1 M phosphate buffer for 30 minutes. Following the reaction, the sections were mounted on gelatin-coated slides and counterstained with neutral red.

thalamus and the pretectum were identified according to data of Updyke (1977), Berman ( 19771, and Avendano and Juretschke (1980).

For the muscimol experiments. After the experimmts, the animals were perfused transcardially in the same manner as in the biocytin experiments. The brains were sectioned into 80-pm serial coronal sections on a freezing microtome and collected in compartmentalized trays. The sections were then mounted on gelatin-coated slides and stained with neutral red,

Each section was examined with both low- and high- magnification lenses by using brightfield illumination. Dis- tributions of labeled terminals or injection sites of muscimol were plotted on sheets of paper with the aid of a drawing tube attached to a microscope. Subdivisions of the

RESULTS Injection sites of biocytin

Tn all five cats, the low-threshold areas for evoking accommodation were generally consistent with the results in our previous study that indicated systematic mapping of the SC (Sawa and Ohtsuka, 1994). The low-threshold sites (evoking accommodation with currents weaker than 20 pA) were located in the superficial and intermediate layers of the rostral SC, in particular, in laminae 111-IV. Biocytin was injected into the low-threshold area in each cat. Before the injections, we confirmed that accommodative responses

ACCOMMODATION SYSTEM IN THE BRAINSTEM 469

were evoked by microstimulation of the injection sites with low current < 20 FA) by using glass micropipettes in all the five cats. Figure 1 shows distributions of injection sites of biocytin and accommodative responses evoked by microstimulation of the injection site. Biocytin injections were confined to small areas in the rostral SC in A 1.6-2.4 in stereotaxic coordinates in all five cats. In cats 10-12, biocytin was injected mainly into laminae IV and V; in cats 5 and 13, biocytin was injected mainly into laminae I11 and IV. Locations of labeled terminals were generally consistent among the five cats.

Ascending projections Following the injection of biocytin into the accommoda-

tion area in the SC: most labeled SC cell axons were found to terminate ipsilaterally in the caudal part of the pretectum (Fig. 2 ) . In particular, the caudal portion of the NOT and the posterior pretectal nucleus (PPN) received many projections. Figure 3 shows a photomicrograph of labeled terminals in the pretectum. The olivary pretectal nucleus (OPN), the anterior pretectal nucleus (APN), and the nucleus of the posterior commissure (NPC) also received many projections. Labeled terminals were also located in the intermediate and deep layers of the rostral SC and in the pretectum on the contralateral side. Some labeled fibers bypassed the NOT in the brachium of the SC (BSC) and terminated ipsilaterally in the posteromedial part of the lateral posterior nucleus of the thalamus (LP), the ventral part of the pulvinar (PL), and most deeply in C laminae of the lateral geniculate nucleus (LGN ). Labeled terminals were also observed in the ipsilateral mesencephalic reticular formation (MRF) at the level of the oculomotor nucleus (OMN). Labeling of terminals in the MRF was stronger in cats 10 and 12, in which the biocytin injection site extended to a deeper part of the rostral SC (see Fig. l), than in the other cats, in which the biocytin injection site extended to a more superficial part of the rostral SC. Sparser terminals are seen in the zona incerta (ZI) and in the magnocellular division of the medial geniculate nucleus (MGNm) on the ipsilateral side.

Descending projections Projections from the accommodation area in the SC are

associated with a certain amount of descending fibers. Figure 4 shows labeled descending fibers and locations of labeled terminals. Two groups of labeled efferent fibers are observed. One group of descending fibers travels laterally and then reaches the brachium of the inferior colliculus (BIC), the MRF, and the parabigeminal nucleus. Relatively few labeled terminals are seen in these nuclei. Most of these descending fibers run ventrally along the medial lemniscus (ML) and terminate in the dorsolateral division of the pontine nuclei and the paralemniscal tegmental field. In contrast, most of the second group of descending fibers turns ventrally around the periaqueductal gray matter and courses ventromedially toward the decussation of Meynert (Fig. 4). After crossing the midline, they descend in the predorsal bundle just ventral to the medial longitudinal fasciculus (MLF). These fibers terminate in the paramedian pontine reticular formation (PPRF), the nucleus raphe interpositus (RIP), and the dorsomedial portion of the nucleus reticularis tegmenti pontis (NRTP) on the contralateral side. Labeling of terminals in the PPRF and thc RIP were stronger in cats 10 and 12, in which the biocytin

injection site extended to a deeper part of the rostral SC (see Fig. I), than in the other cats, in which the biocytin injection site extended to a more superficial part of the rostral SC. Some of the fibers of this group terminated in the ipsilateral MRF.

Muscimol injection We injected muscimol into the pretectal area at A 5.0-5.5

in stereotaxic coordinates in three cats. The injections in each cat had qualitatively the same effect as those in the other cats. Accommodative responses to microstimulation of the SC were compared before and after the injections. Accommodative amplitude was calculated from the average of 10 responses during each period. The effect of muscimol appeared in less than 10 minutes and lasted for 2-4 hours. Histological examinations revealed that the injection sites, the areas stained by fast green, were confined to the pretectal area including the NOT, the YPN, and the NPC but that muscimol was diffused into neither the SC nor the MRF in the three cats. Figure 5B shows the effect of muscimol injection on accommodative responses evoked by microstimulation of the SC in one cat. Before the injections, accommodative responses were evoked consistently by microstimulation of a low-threshold site in the SC with currents weaker than 20 FA. Following muscimol injections, the amplitude of accommodative responses was reduced to 33-55% of the value before the injections. The effect of muscimol was abolished gradually within 2-4 hours after the injections. The minimal effective dose of muscimol was about 0.1-0.2 p1. Accommodative responses could not be abolished, even when 1.0 p1 of muscimol was injected.

DISCUSSION The present experiments demonstrated that the accom-

modation area in the rostral SC projects mainly to the ipsilateral pretectal area and the MRF as ascending projections and to the NRTP, the PPRF, and the RIP on the contralateral side and the pontine nuclei on the ipsilateral side as descending projections. All of these areas are thought to be involved in oculomotor-related functions. The NOT, the NPC, and the MRF have important roles in the control of accommodation and/or vergence eye movements (Hultborn et al., 1978a; Bando et a1 , 1984a; Mays, 1984; Judge and Cumming, 1986; Konno and Ohtsuka, 19951, and the OPN and the PPN are involved in the control of pupillary movements (Gamlin et a]., 1984; Trejo and Cicerone, 1984; Clarke and Ikeda, 1985a,b). The PPRF and the RIP are involved in the control of saccades and visual fixation, respectively (Keller, 1974; Ruttner et d., 1977; Hepp and Henn, 1983; Langer and Kaneko, 1983; Fuchs et al., 1985; Strassmann et al., 1987; Munoz and Guitton, 1991; Munoz and Wurtz, 1993).

Pretectum Hultborn et al. (1978a) reported that microstimulation of

the pretectum evoked the early potential of the short ciliary nerve, which innervates the ciliary nerve. Recently, we conducted systematic mapping of the pretectal area with microstimulation, monitoring accommodation by using an infrared optometer, and reported that low-threshold areas for evoking accommodation were confined to the posterolat- era1 part of the pretectum corresponding to the NOT, the

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ACCOMMODATION SYSTEM I N THE BK4INSTEM 471

Fig 3. Photomicrograph shows labeled terminals in the caudal part of'the NOT. The section is from cat 13. Scale bar = 50 km.

OPN, and the PPN and to the medial part of the pretectum corresponding to the NPC (Konno and Ohtsuka, 1995). These low-threshold areas were in general comparable to the terminal areas in this study. When cell activities in the pretectum were inhibited by muscimol injection, the amplitude of accommodative responses evoked by microstimulation of the rostral SC was reduced, although evoked accommodation was not abolished. These findings suggest that some fibers carrying signals for controlling accommodation from the SC synapse in the pretectum, although there is a possibility that the these fibers project to other neural substrates.

The OPN and PPN are also thought to be involved in thr control of pupillary movement. Two types of neurons in the OPN and the PPN, which are sensitive to changes in light level, have been described (Clarke and Ikeda, 1985a). One type, called luminance detectors and located in the OPN, showed a graded increase in firing rate with increase in luminance. The other type, called darkness detectors and located in the PPN, showed a graded increase in firing rate with decrease in luminance. The OPN may be involved in pupillary constriction, and the PPN may be involved in pupillary dilation. Constriction of the contralateral pupil was induced by microstimulation of the OPN (Trejo and Cicerone, 1984). The accommodation area in the rostral SC projects to the OPN and the PPN. Accommodation and pupillary movement are closely linked with each other in the ocular near response. It is likely that the connection

between the rostral SC and the pretectum provides the basis for the link between accommodation and pupillary movement in the ocular near response.

MRF In the present study, labeled terminals in the MRF were

more pronounced in the cats in which biocytin was injected mainly into the intermediate and deep layers of the rostral SC. Previous studies have also indicated that the MRF receives projections mainly from the intermediate and deep layers but not from the superficial layers of the SC (Gra- ham, 1977). Neurons that exhibited discharge preceding accommodation, convergence, or both were found in the MRF (Bando et al., 1984a; Mays, 1984; Judge and Cum- ming, 1986). These cells were confined to a small region dorsolateral to the uculomotor nucleus in both the cat and the monkey. In this study, labeling of terminals was found in the portion dorsolateral to the oculomotor nucleus, which must be comparable to the accommodation-vergence area in the MRF. Accommodation and vergence eye movement are closely linked with each other in the ocular near response (Alpern, 1969; Miles, 1985). A previous study has suggested that the SC is also involved in the control of vergence eye movements (Cowey et al., 1984). It is likely that the connection between the rostral SC and the MRF provides the basis for the link between accommodation and vergence in the ocular near response.

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ACCOMMODATION SYSTEM IN THE BRAINSTEM 473

A Muscimol -n-’

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A B Accommodation

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Fig. 5. A: Schematic diagram shows the methods used for muscimol injections into the pretectum, microstimulation of the rostral SC. and monitoring of accommodative responses. B: Examples of accommodative responses evoked by microstimulation of the rostral SC before and after the injections of muscimol into the pretectum. The horizontal bar above the time scale in B indicates the period of stimulation.

PPRF and RIP Both the PPRF and the RIP are in the oculomotor-

related premotor region. It is well-known that a specific group of neurons in the PPRF exhibits burst discharges for saccade generation (Fuchs et al., 1985). Many studies have indicated that the intermediate and deep layers of the SC project to the contralateral PPRF (Harting et al., 1973; Graham, 1977; Kawamura and Hashikawa, 1978; Huerta and Harting, 1982). However, the RIP has been indicated as the location of omnipause neurons, which are tonically active in all periods of fixation and pause during saccades (Luschei and Fuchs, 1972; Keller, 1974; Evinger et a]., 1982; Strassman et al., 1987; Buttner-Ennever et al., 1988). Omnipause neurons project to burst neurons in the PPRF and inhibit their activities during fixation. Recently, the rostral SC has been shown to be involved in the control of active visual fixation in both the monkey and the cat (Munoz and Guitton 1989,1991; Munoz et al., 1991; Munoz and Wurtz, 1993). Neurons in this portion also exhibit tonic discharges during fixation. Fixation neurons are thought to project to omnipause neurons in the RIP in both the monkey (Raybourn and Keller, 1977; Buttner-Ennever et al., 1988) and the cat (King et al., 1980; Munoz and Guitton 1989, 1991; Pare and Guitton 19941, and to control the activity of omnipause neurons in the RIP (Munoz and Wurtz, 1993).

Pontine nuclei and NRTP Pontine nuclei and the NRTP are the precerebellar

nuclei, which project to large areas of the cerebellum (Hoddevik, 1978; Brodal, 1979). The present study indicates that the accommodation area in the rostral SC projects to the dorsolateral pontine nucleus and the dorsomedial portion of the NRTP. These portions are primary sources of afferents to the flocculus and vermal lobules VI and VII (Brodal, 1979; Langer et al., 19851, which are involved in the control of saccades, smooth-pursuit eye movements, and fixation (Lisberger and Fuchs, 1978; Noda

and Suzuki, 1979; Kase et al., 1980). In addition, accommodation was evoked by stimulation of the cerebellar nuclei, i.e., the interpositus nucleus and the fastigial nucleus (Hosoba et al., 1978; Hultborn et al., 1978b). This evoked accommodation was suppressed when stimulation of the cerebellar nuclei was preceded by stimulation of the vermal area (lobules VI and VII; Hultborn et al., 197813). It is known that the interpositus nucleus projects to the parasympathetic oculomotor neurons with a short (mono- or disyn- aptic) latency (Hultborn et al.. 1978b). Some studies have suggested that the cerebellum is also involved in the control of vergence eye movements. Ablation of the cerebellum in the monkey transiently impairs vergence (Westheimer and Blair, 1973). Purkinje cells in the flocculus exhibit discharges related to the near response (Miles et a]., 1980).

Functional considerations The present study suggests that the rostral SC projects to

accommodation (NOT, PPN and NPC), vergence-related (MRF), pupillary (OPN and PPN) and omnipause (RIP) areas (Fig. 6). Convergence, accommodation, and pupilloconstriction form the triad of the ocular near response, which provides a single and clear retinal image and forms an essential basis for fine vision (Alpern, 1969). Active fixation may be functionally linked with the near response. The active fixation system inhibits saccadic eye movements and facilitates stable foveal fixation. Therefore, it is likely that the rostral SC is involved in the control of not only accommodation but also vergence eye movements and active fixation. Previous studies support this hypothesis (Berman et al., 1975; Cowey et al., 1984; Munoz and Guitton 1989, 1991; Munoz et al., 1991; Munoz and Wurtz, 1993). Fixation neurons in the SC are located in the intermediate layers of the portion corresponding to the area of representation of the central visual field (Munoz and Wurtz, 1993), and the accommodation area is located in the superficial and intermediate layers of the rostral SC corresponding to the area of representation of the central visual

474 A. SAT0 AND K. OHTSUKA

LS (Cortical accommodation

and vergence area)

Accommodation area Fixation area

Rostra1 SC

+ + + lo

0

Fixation system Vergence system

*Accommodation system I WPupillary constriction system

Fig. 6. Schematic diagram shows affcrcnt and efferent pathways of the rostral SC, indicating i ts involvement in the control o f t h e ocular near response and active fixation in the cat.

field (Sawa and Ohtsuka, 1994). The accommodation area may be overlapped ventrally by the fixation area in the rostral SC (Fig. 6).

The accommodation area in the SC receives heavy projections from the accommodation area in the LS of the cat cortex (Maekawa and Ohtsuka, 1993). It is well-known that the LS is also involved in the control of' vergence eye movements and pupilloconstriction (Bando, 1985; Toda et al., 1991; Maekawa and Ohtsuka, 1993). In the monkey, fixation cells have been identified in area 7a of the posterior parietal cortex (Mountcastle et al., 1975; Lynch et al., 1977; Sakata et al., 1980). These fixation cells are analogous to the fixation cells in the SC (Munoz and Wurtz, 1993). Area 7a of the monkey is thought to be analogous to the LS of the cat (Heath and Jones! 1971). The posterior parietal cortex of the monkey also projects to the rostral SC (Lynch et al., 1977). These studies suggest that the rostral SC receives signals controlling accommodation, pupilloconstriction, vergence eye movements, and active visual fixation from the posterior parietal cortex and projects to the portions related to each of these functions in the brainstem (see Fig. 6). We conclude that the rostral SC is likely a key structure in the control of the ocular near response and active fixation.

CONCLUSIONS The present results indicate that the accommodation-

related region in the rostral SC projects to the pretectum, the MRF, and the RIP, which are related to accommodation, vergence, and active fixation, and that fibers carrying accommodation signals from the rostral SC project to the oculomotor nucleus partially through the pretectum.

ACKNOWLEDGMENTS This study was supported by Grants-in-Aid for Scientific

Research from the Japanese Ministry of Education, Science

and Culture (04771362, 04807129). We thank Masahiro Sawa, Tomihiro Imai, and Yutaka Fujito for excellent technical assistance and Professor Takashi Nakagawa for valuable comments on this manuscript.

LITERATURE CITED Alpern, M. (1969) Accommodation. In H. Davson (ed): The Eye, vol. 3:

Muscular Mechanisms. New York: Academic Press, pp. 21 7-249. Avendano. C., and M.A. Juretschke (1980) The pretectal region of the cat: A

structural and topographical study with stereotaxic coordinates. J. Comp. Ncurol. 19.?:69-88.

Bando, T. (1985) Pupillary constriction evoked from the posterior medial lateral suprasylvian (PMLS) area in cats. Neurosci. Res. 2:472-485.

Bando, T., K. Tsukuda, N. Yamamoto. J. Maeda, and N. Tsukahara (1981) Cortical neuruns in and around the Clare-Bishop area related with lens accommodation in the cat. Brain Kes. 225:195-199.

Bando, T.. K. Tsukuda, N. Yamamoto, J . Maeda, and N. Tsukahara (1984a) Physiological identification of midbrain neurons related to lens accommodation in rats. J. Keuruphysiol. 52:870-878.

Bando, T., N. Yamamoto, and N. Tsukahara 11984b) Cortical neurons related to lens accommodation in posterior lateral suprasylvian area in cats. J. Neurophysiol. 52879-891.

Benevento. L.A., and J H. Fallon (1975) The ascending projections of the superior colliculus in the rhesus monkey (Mucaca mukzta). J. Comp. Neurol. I GO: 339-362.

Berman, N. (1977) Connections ofthoprctcctum in the cat. J. Comp. Neurol. 174:227-254.

Rerman. N., C. Blakemore, and M. Cynader (1975) Binocular interaction in the cat's superior colliculus. J. Physiol. (1,nnd.r 246:595-615.

Brodal, P. (1979) The piintocerebellar projection in the rhesus monkey: An cxpcrimental study with retrograde axonal transport of horseradish peroxidase. Neuroscience 4: 193-208.

Buttncr, U. , J.A. Ruttncr-Ennever, and V. Hcnn (1977) Vcrtical eye movement related unit activity in the rostral mesencephalic reticular formation of the alert monkey. Brain Res. 130:239-252.

Biittncr-Ennever, J.A., B. Cohen, M. Pause, and W. Fries (1988) Raphe nucleus of the pons containing omnipause neuron of the oculomotor system in the monkey, and its homologue in man. J . Comp. Ncurol. 267;307-321.

ACCOMMODATION SYSTEM IN THE BKAINSTEM 475

Clarke, R.J., and H. Ikeda (1985aJ Luminance and darkness dctcctors in the olivary and posterior pretectal nuclei and their relationship to the pupillary light reflex in the rat. I . Studies with steady luminance levels. Exp. Brain Res. 57:224 232.

Clarke, R.J., and H. Ikeda (1985h) Luminance and darkness detectors in the olivary and posterior pretectal nuclei and their relationship to the pupillary light reflex in the rat. 11. Studies using sinusoidal light. Exp. Brain Res. 59:83-90.

Cornswect, T.N., and H.D. Crane (1970) Scrvo-controlled infrared optometer. J. Optic. SOC. Am. 60:548-554.

Cowey, A,, B. Smith, and C.M. Butter (1984) Effects of damage to superior colliculi and pretectum on movement discrimination in rhesus monkeys. Exp. Brain Res. 56:79-91.

Evinger, C., C.R.S. Kaneku, and A.F. Fuchs (1982) Activity of omnipause neurons in alert cats during saccadic eye movements and visual stimuli. J. Neurophysiol. 47:827-844.

Fuchs. A.F., C.R.S. Kaneko. and C.A. Scudder (19851 Brainstem control of saccadic eye movements. Ann. Rev. Neurosci. R:307-337.

Gamlin P.D.R., A. Reiner, J.T. Erichsen, H.J. Karten, and D.H. Cohcn (1984) The neural substrate for. the pupillary light reflex in the pigion ICoZumba liuza). J. Comp. Neurol. 226:523-543.

Giolli, R.A., G.M. Paterson, C.E. Ribak, H.M. McDonald, R.H.I. Blanks. and J.H. Fallon (19%) GARAergic neurons comprise a majur cell type in rodent visual relay nuclei: An immunocytochemical study of pretectal and accessory optic nuclei. Exp. Brain Res. 61~194-203.

Graham, J. (1977) An autoradiographic study ur the effcrcnt connections of the superior colliculus in the cat. J. Comp. Neurol. 17,?:629-654.

Harting, J.K., W.C. Hall. I.T. Diamond, and G.F. Martin (1973) Anterogade degeneration study of the superior colliculus in Tupin glia: Evidence for a subdivision between superficial and deep layers. J. Comp. Neurol. 1483361-386,

Harting, J.K., M.F. Huerta, A.J. Frankfurter, N.L. Strominger, and G.J. Royce 11980) Ascending pathway from the monkey superior colliculus: An autoradiographic analysis. J. Comp. Neurol. 192853-882.

Heath, C.J., and E.G. Jones 11971) 'The anatomical organization of the suprasylvian p u s ofthe cat. Ergebn. Anat. EntwGcsch. 45:l-64.

Hepp, K., and V. Henn (1983) Spatio-temporal recording of rapid eye movement signals in the monkey paramrdian pontine reticular formation (PPRF). Exp. Brain Res. 52r105-120.

Hoddevik, G.H. (1978) The projection from nucleus reticularis tegmenti pontis onto the cerebellum in the cat. A study using the methods of antcrograde degeneration and retrograde axonal transport of horseradish peroxidase. Anat. Enibryol. 15.?:227-242.

Hosoba, M., T. Bando, and N. Tsukahara (1978) Thc cerebellar control of accommodation of the eye in the cat. Brain Res. 153:495-505.

Hucrta, M.F., and J.K. Harting (1982) Projection of the superior colliculus to the supraspinal nucleus and thecervical spinal cord gray of the cat. Brain Res ,242: 326-33 1.

Hultborn, H., K. Mori, and N. Tsukahara (1978a) The neuronal pathway suhserving the pupillary light reflex. Brain Res. 159:255-267.

Hultborn. H.: K. Mori. and N. Tsukahara 11978hl Cerebellar influence on parasympathetic neurons innervating intra-ocular muscles. Brain Res. 159:269-278.

Judge, S.J., and B.G. Cumming (19861 Neurons in the monkey midbrain with activity related to vergence eye movement and accommodation. J. Neurophysiol. ,55915-930.

Kase, M., D.C. Miller, and H. Noda 11980) Discharge of Purkinje cells and mossy fibers in the cerebellar vcrmis of the monkey during saccadic eye movements and fixation. J. Physiol. (Lond.1300:539-555.

Kawamura. K., and T. Hashikawa (1978) 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.

Kawamura, S., J.M. Spraugue, and K. Niimi (1974) Corticofugal projections from the visual cortices to the thalamus, pretectum and superior colliculus in the cat. J. Comp. Ncurol. 158:339-362.

Keller, E.L. (19741 Participation of medial pontine reticular formation in eye movement generation in monkey. J. Neurophysiol. 37~316-332.

King, W.M., W. Precht, and W. Dieringer (1980) Afferent and eFFerent. connect;ons of cat Omnipause neurons. Exp. Brain Res. 38:395-403.

Konno, s,, and K. Ohtsuka (19953 Accommodation-related arcs in the preteck31 nuclei of the cat. Invest. Ophthalnlol. Vis. S C i . %?6:694.

Kubota, T,, M, ~ ~ ~ i ~ ~ t ~ , T. Kanaseki, and 11. Inomata (1989) Projection

from the superficial layers of the tectum to the pretectal complex in the cat. Brain Res. Bull. 22:373-378.

Langer, T.P., and C.R.S. Kaneko (1983) Efferent projections of the cat oculomolor reticular umnipause region: An autoradiographic study. J. Comp. Neurol. 21 7:288-306.

Langer. T.P., A.F. Fuchs. C.A. Scudder; and M.C. Chubb (19853 Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase. J. Comp. Neurol. 295: 1- 25.

Lisberger, S.G., and A. Fuchs (1978) A role of primate flovculus during rapid behavioral mudificatiun oC vestibuloocular reflex. I. Purkinjr cell activity during visually guided horizontal smooth-pursuit eye movement and passive head rotation. J. Neurophysiol. 41:733-763.

Luschei, E.S., and A.F. Fuchs (1 972) Activity of brain stem neurons during eye movements of alert monkeys. J. Neurophysiol. 354455461,

Lynch, T.P., V.R. Moutcastle, W.H. Talbut, and T.C.T. Yin (19771 Parietal lobc mechanisms for directed visual attention. J. Neurophysiol. 40:362- 369.

Maekawa, H., and K. Ohtsuka (1993) Afferent and efferent connections of the cortical accommodation area in the cat. Neurosci. Res. 17r315-323.

Mays, L.E. (1984) Neural control of vergence eye movements: Convergence and divergence neurons in midbrain. J . Neurophysiol. 51:1091-1108.

Miles, F.A. (19851 Adaptive regulation in the vergence and accommodation control systems. In A. Berthoz and G. Melvill Jones (eds): Adaptive Mechanisms in Gaze Control, Facts and Theories. Amsterdam: Elsevier, pp. 81-94.

Miles, F.A., J.H. Fuller, D.J. Braitman, and B.M. Dow (19801 Long-term adaptive changes in primate vestihuloocular reflex. 111. Electrophysinlogi- cal observations in flocculus of normal monkeys J Neurophysiul. 43: 1437-1476.

Mountcastle, V.B., J.C. Lynch, A. Georgopoulos, H. Sakata, and C. Acuna (1975) Posterior parietal association cortex of the monkey: Command functions for operations within extrapersonal space. J. Neurophysiol.

Munoz, D.P.. and D. Guitton (19891 Fixation and orientation control by the tecto-reticulo-spinal system in the cat whose head is unrestrained. Rev. Neurol. (Paris1 145567679.

Munoz, D.P., and D. Guitton (1991) Control of orienting gaze shifts by the tectoreticulospinal system in the head-free cat. 11. Sustained discharges during motor preparation and fixation. J. Neurophysiol. 66:1624-1641.

Munoz. D.P., and R.H. Wurtz 11993) Fixation cells in monkey superior colliculus. I. Characteristics of cell discharge. J. Neurophysiol. 70:559- 575.

Miinoz, D.P., D. Guittun, and D. Pelisson (1991) Control of orienting gaze shifts by the tector.eticulo.;pinal system in the head-free cat. 111. Spatio- temporal characteristics uf phasic motor discharges. J. Neurophysiol. 66':1642-1666.

Noda, H., and D. Suzuki (1979) The role of the flocculus of the monkey in fixation and smooth pursuit eye movements. J. Physiol. (Lond.) 294:335- 348.

Norita. M.. J.G. McHafIie, H. Shimizu, and B.E. Stein(l99li Thccorticostria- tal and corticotectal projections of the feline lateral mprasylvian cortex demonstrated with anterograde hincytin and retrograde fluorescent techniques. Neurosci. Res. 10:149-155.

Ohtsuka, K., and K. Sato (19981 Descending projections from the cortical accoininodation area in the cal. Invesl. Ophthalmol. Vis. Sci. (in press).

Pare, M.: and D. Guitton (1994) The fixation area of the cat superior colliculus: Effects of electrical stimulation and direct connection with brainsteni omnipause neurons. Exp. Brain Res. 101:109-122.

Penny. G.R., M. Conley, U.E. Schmechel, and I.T. Diamonds (1984) The distribution of glutamic acid decarboqdase imniunoreactivity in the diencephalon of the opposum and rabbit. J. Comp. Neurol. 228:38-56.

Raybourn. M.S., and E.L. Keller (1977) Colliculo-reticular organization in primate oculomotor system. J. Neurophysiol. 40:861 878

Ripps, H., 1.M. Siege], and W.R. Gctz (1962) Functional organization of ciliary muscle in the cal. Am. J. Physiol. 203857-859.

Sakata, H., H. Shibutani, and K. Kawano (1980) Spatial properties of visual fixation neurons in posterior parietal association cortex of Lhe monkey. J. Neurophysiol. 43: 1654-1672.

Saaa. M.. and K. Ohtsuka (1994) Lens accommodation evoked by microstimulation ofthe superior colhculus m the cat. Visinn Res. 34:975-981.

saws, M., H. Maekawa, and K. Ohtsuka t19Y'') Cortical area re1att.d to 1 - 7 ~

accommodation in cat. Jpn. *J. Ophthalmol. 36:371-379-

talprojection in cats. J. Comp. Neurol. 225:259-275.

38:s 71-908.

segal, R,J+ and R, M. Beckstcad (1984) Thc lateral SUPrasYlvian corticotec-

476 4. SAT0 AND K. OHTSUKA

Clare-Bishop neurons t.o motion cues for motion stereopsis. Neurosci. Res. 4:83-109.

Trejo, T..d. , and C.M. Cicerone (1984) Cells in the pretectal olivary nucleus are i n thc pathway for the direct light reflex of the pupil in the rat. Brain Rcr. 300:49-62.

Updyke, B.V. (19771 Topographic organization of the projections rrom cortical areas 17, 18, and 19 onto the thalamus, pretectum and superior colliculus. J. Camp. Neural. 17323-122.

Updyke. B.V. (1981) Projections from visual areas oft,he middle suprasylvian sulcus onto the lateral posterior complex and ail.jacent thalamic nuclei in cat. J. Comp. Neurol. 201.477-506.

Westheinier, G., and S.M. Blair (1973) Oculomotor defects in cerebellecto- mized monkeys. Invest. Ophthalmol. Vis. Sci. 12618-621.

Strassman, A., C. Evinger, K.A. McCrea, R.G. Baker, and S.M. Highstein (1987) Anatomy and physiology of intracellularly labelled omnipmse neuronsin the cat and squirrel monkey. Exp. Brain Res. 67:436-440.

Toda. H., M. Takagi; T. Yoshizawa, and T. Bando (1991) Disjunctive eye movement evoked by microstimulation in an extrastriate cortical area of the cat. Neurosci. Res. 12300-306.

‘I‘oyama, K.. and T. Kuzasa 11982) Responses of Clare-Bishop neurons to three-dimensional movenient of a light stimulus. Vision Res. 22571-574.

Toyama, K., K. Fujii. S. Kasai, and K. Maeda (1986a) The responsiveness uf Clare-Bishop neurons to size cues for motiun stcrcopsis. Neurosci. Res.

Toyania, K., Y. Komatsu, and ‘r. Kozasa (1986b) The responsivcncss of 4: I I 0-128.

Projection from the accommodation-related area in the superior colliculus of the cat

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