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THE JOURNAL OF COMPARATIVE NEUROLOGY 407:318–332 (1999)
Projections of the Vestibular Nuclei to the Thalamus in the Rat: A Phaseolus vulgaris Leucoagglutinin Study TAKASHI SHIROYAMA,1 TETSURO KAYAHARA,1 YUKIHIKO YASUI,2 JUNICHI NOMURA,3 AND KATSUMA NAKANO1* 1Department of Anatomy, Faculty of Medicine, Mie University, Tsu, Mie 514, Japan 2Department of Anatomy, Shimane Medical University, Izumo, Shimane 693, Japan 3Department of Psychiatry, Faculty of Medicine, Mie University, Tsu, Mie 514, Japan
ABSTRACT Injections of the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin were made into individual nuclei of the vestibular nuclear complex of the rat to identify specific projections to the thalamus. The results showed that the superior vestibular nucleus and the medial vestibular nucleus, especially its rostral-to-middle parts, project to the lateral part of the parafascicular thalamic nucleus (corresponding to the centromedian nucleus in primates), the transitional zone between the ventrolateral thalamic nucleus (VL) and the ventral posterolateral thalamic nucleus (VPL) (the region considered to be the nucleus ventralis intermedius of Vogt [Vogt C. 1909. La myeloarchitecture du thalamus du cercopitheque. J Psychol Neurol 12:285–324.]), the lateral part of the centrolateral thalamic nucleus and the dorsal part of the caudal VL; the spinal vestibular nucleus projects to the lateral part of the parafascicular thalamic nucleus, the transitional zone between the VL and the VPL, the caudal part of the ventrobasal complex, and the suprageniculate thalamic nucleus. These results suggest that vestibular information is transmitted not only to the cerebral cortex (mainly area 2V and area 3a) but also to the striatum. They also suggest that vestibular activity may affect gaze control by means of vestibulothalamocortical pathway in addition to vestibulo-ocular and vestibulopremotoneuronal routes. J. Comp. Neurol. 407:318–332, 1999. r 1999 Wiley-Liss, Inc. Indexing terms: corpus striatum; saccades; brain stem; frontal eye field; centromedian nucleus
The vestibular nuclear complex (VN) has been shown to project rostrally to the extraocular motoneurons (i.e., the abducens, trochlear, and oculomotor nuclei) (Carleton and Carpenter, 1983; Carpenter and Cowie, 1985; McCrea et al., 1987a,b), to additional brainstem nuclei, including the interstitial nucleus of Cajal (for review see Bu¨ttnerEnnever and Bu¨ttner, 1988), to the cerebellum (Brodal and Brodal, 1985), and to the cerebral cortex (mainly area 2V and area 3a) by means of the thalamus (for review see Fredrickson and Rubin, 1986). The vestibular inputs to the extraocular motoneurons (vestibulo-ocular route) and the additional brainstem nuclei, including the interstitial nucleus of Cajal, are involved in the vestibulo-ocular reflex (for review see Leigh and Brandt, 1993; Bu¨ttner-Ennever and Bu¨ttner, 1988). The VN provides the cerebellum with information about head velocity, eye velocity, and position (Cheron et al., 1996). The vestibulothalamic projections were originally described by the degeneration method (Hassler, 1948, 1972; Carpenter and Hanna, 1962; Carpenter and Strominger,
r 1999 WILEY-LISS, INC.
1965; Raymond et al., 1974), although these projections were denied by some authors (Brodal and Pompeiano, 1957; Tarlov, 1969). Existence of this pathway was established by autoradiographic studies (Raymond et al., 1976; Lang et al., 1979). Subsequently, retrograde axonal tracing methods that used either horseradish peroxidase (HRP) (Conde´ and Conde´, 1978; Magnin and Kennedy, 1979; Kotchabhakdi et al., 1980; Maciewicz et al., 1982; Nakano et al., 1985) or wheat germ agglutinin-HRP (WGA-HRP)
Grant sponsor: Ministry of Education, Science, Sports, and Culture of Japan; Grant number: Grants-in-Aid for Scientific Research 03670022; Grant number: Grants-in-Aid for Scientific Research 08680814. Dr. Takashi Shiroyama’s present address is Department of Psychiatry, Faculty of Medicine, Mie University, Tsu, Mie 514-8507, Japan. *Correspondence to: Dr Katsuma Nakano, Department of Anatomy, Faculty of Medicine, Mie University, Tsu, Mie 514-8507, Japan. E-mail: [email protected]
Received 13 January 1998; Revised 16 July 1998; Accepted 4 December 1998
VESTIBULAR PROJECTIONS TO THE THALAMUS (Nagata, 1986) have further revealed thalamic projections from the VN. However, a review of the literature reveals considerable disagreement between the various studies as to which parts of the thalamus are innervated by which vestibular nuclei (Jones, 1985). Some recent studies have proposed ‘‘new’’ vestibular cortical areas, such as the posterior parietal association cortex (area 7) (Kawano et al., 1980; Kawano and Sasaki, 1984; Faugier-Grimaud and Ventre, 1989) and insular cortex (Gru¨sser et al., 1990a,b; Guldin et al., 1992; Akbarian et al., 1992). A recent positron emission tomography (PET) study (Bottini et al., 1994) reported activation in the putamen with vestibular stimulation in man. Another PET study in man (Bottini et al., 1995) indicated that touch and vestibular signals share projections to the putamen, insula, somatosensory area II, premotor cortex, and supramarginal gyrus. More detailed information on the possible thalamic relay that might transmit vestibular activity would, therefore, be useful to understand the ascending vestibular system. In the present study, the use of the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) has enabled us to make injections confined to individual nuclei of the vestibular complex, thereby defining the ascending projections relatively unambiguously.
MATERIALS AND METHODS The experiments were performed on adult albino rats of either sex weighing 250–350 g. The animals were cared for in accordance with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals and the guidelines of the Faculty of Medicine, Mie University. In 25 rats, injections of PHA-L (Vector Laboratories, Burlin-
319 game, CA) were made into the respective parts of the vestibular nuclei under intraperitoneal chloral hydrate anesthesia (280 mg/kg). In each rat, a single injection was made by iontophoresis through a glass micropipette filled with a 2.5% PHA-L solution in 0.01 M phosphate buffer (pH 7.6) under stereotaxic control according to the atlas of Paxinos and Watson (1986). The driving current (5–7 µA, 200-ms duration, 2 Hz) was delivered for 15–25 minutes. After a survival period of 10–14 days, the rats were reanesthetized deeply and perfused transcardially with 200 ml of saline, followed by 500 ml of a solution of 8% formalin and 0.2% glutaraldehyde in 0.1 M phosphate buffer (pH 7.3) and then with 200 ml of the same buffer containing 10% sucrose. The perfused brains were removed and placed in a cold solution of 25% sucrose in the same buffer at 4°C for 2 days. Subsequently, the brains were cut serially into frontal sections of 50-µm thickness on a freezing microtome. After a brief wash in phosphate-buffered saline (PBS), the sections were divided into three series; two series were processed with the avidin-biotin-peroxidase complex (ABC) method (Gerfen and Sawchenko, 1984; Gerfen et al., 1989), and one series was not immunoreacted but counterstained with 1% cresyl violet. The sections to be immunostained were incubated in PBS, pH 7.3, containing 0.25% triton X-100 and 3% normal goat serum (PBS-goat) for 60 minutes at room temperature, and incubated in PBS-goat containing rabbit anti PHA-L (Vector; 1:3,000) overnight at 4°C. After rinsing in PBS, the sections were incubated in PBS-goat containing biotinylated goat anti-rabbit IgG for 3 hours at room temperature, rinsed in PBS, and then incubated in PBS containing avidin-biotin-horseradish peroxidase for 60 minutes at room temperature. Subse-
Abbreviations 7 7n 8n AD AM APT APTD AV C CeM CL CM CG DC ECu eml FEF fr G g7 ic icp intA jx Lat LD LGD LGV LHb Li LP LVN MD Med MG
facial nucleus facial nerve vestibulocochlear nerve anterodorsal thalamic nucleus anteromedial thalamic nucleus anterior pretectal area dorsal part of the anterior pretectal area anteroventral thalamic nucleus cochlear nucleus centromedian thalamic nucleus centrolateral thalamic nucleus central medial thalamic nucleus central gray dorsal cochlear nucleus external cuneate nucleus external medullary lamina frontal eye field fasciculus retroflexus gelatinosus thalamic nucleus genu of the facial nerve internal capsule inferior cerebellar peduncle anterior part of the interposed cerebellar nucleus juxtarestiform body lateral cerebellar nucleus lateral dorsal nucleus dorsal part of the lateral geniculate nucleus ventral part of the lateral geniculate nucleus lateral habenular nucleus limitans thalamic nucleus lateral posterior thalamic nucleus lateral vestibular nucleus mediodorsal thalamic nucleus medial cerebellar nucleus medial geniculate body
MGD MGM MGV MHb ml mt MVN Pc PF Po PrH PT PVA Rt scp SG sp5 Sp5O Sp5I str SuVN SpVN unc VB complex Vim VL VLo VLc VM VPI VPL VPM VPMpc ZI
dorsal nucleus of the medial geniculate body magnocellular nucleus of the medial geniculate body ventral nucleus of the medial geniculate body medial habenular nucleus medial lemniscus mamillothalamic tract medial vestibular nucleus paracentral thalamic nucleus parafascicular thalamic nucleus posterior thalamic nucleus prepositus hypoglossal nucleus paratenial thalamic nucleus anterior part of the paraventricular thalamic nucleus reticular thalamic nucleus superior cerebellar peduncle suprageniculate thalamic nucleus spinal trigeminal tract oral part of the spinal trigeminal nucleus interpolar part of the spinal trigeminal nucleus superior thalamic radiation superior vestibular nucleus spinal vestibular nucleus uncinate fasciculus ventrobasal complex nucleus ventralis intermedius ventrolateral thalamic nucleus oral part of the ventrolateral thalamic nucleus caudal part of the ventrolateral thalamic nucleus ventromedial thalamic nucleus ventral posterior inferior thalamic nucleus ventral posterolateral thalamic nucleus ventral posteromedial thalamic nucleus parvocellular part of the ventral posteromedial thalamic nucleus zona incerta
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Fig. 1. A–F: The sites of Phaseolus vulgaris leucoagglutinin injection in 25 cases investigated in the present study, indicated by the areas drawn with broken lines in a series of standard diagrams of frontal sections in rostrocaudal order. For abbreviations, see list. V refers to experimental number.
quently, one series of sections were rinsed in PBS, incubated in 0.1 M phosphate buffer (pH 7.3) containing 3,38-diaminobenzidine (0.04%) and H2O2 (0.01%). With the other series of sections, immunoreactivity was intensified by adding 1% nickel ammonium. After rinsing in PBS, sections were mounted onto gelatinized slides and coverslipped with Canada Balsam. The extent of the injection sites and distribution of anterogradely labeled fibers and terminals were observed by comparison with the counterstained series of serial sections and one of the immunostained series which were reprocessed for counterstaining with 1% neutral red.
RESULTS PHA-L injection sites of 25 rats are shown in Figure 1. Rats were divided into five groups based on the injection sites: PHA-L was injected into the superior vestibular nucleus (SuVN) in three rats, the rostral-to-middle parts of the medial vestibular nucleus (MVN) in seven rats, the caudal part of the MVN in five rats, the lateral vestibular nucleus (LVN) in five rats, and the spinal vestibular nucleus (SpVN) in five rats. Only one representative case of each group will be described in detail.
Injections in the superior vestibular nucleus In V18, the injection site was located in the central portion of the SuVN and only slightly involved the dorsal part of the LVN (Figs. 1B, 2A, 3). In this case, labeled fibers and terminals in the thalamus were distributed mainly in the lateral part of the parafascicular nucleus (PF), centrolateral nucleus (CL), the nucleus paracentralis (Pc), caudal part of the ventrolateral nucleus (VL) (VLc), ventral posterolateral nucleus (VPL), transitional zone between the posterior thalamic nucleus (Po) and the ventral posteromedial nucleus (VPM) (Po-VPM), the ventral part of the lateral geniculate nucleus (LGV), and ventromedial nucleus (VM) (Fig. 2B–E). No labeled fibers and terminals were found in the suprageniculate nucleus (SG) or medial geniculate body (MG). Labeled axon terminals in the PF were distributed in the dorsolateral part, bilaterally with an ipsilateral dominance (Fig. 2E). Few labeled fibers and terminals were found in the medial and ventrolateral parts of the PF. Some labeled axons ascending through the CL were observed to constitute a dense plexus of labeled axon terminals in the border region between the lateral CL and the dorsal VLc (CL-VLc) (Fig. 2D). More rostrally, a small number of labeled fibers with bouton-like varicosi-
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Fig. 2. Projection drawings of frontal sections arranged rostrocaudally, showing a site of Phaseolus vulgaris leucoagglutinin injection (shaded area in A) into the superior vestibular nucleus (A) and resulting anterograde labeling in the thalamus (B–E). For abbreviations, see list.
small patches of axon terminals mainly in the contralateral transitional zone between the VL and the VPL (VLVPL) (Fig. 2C) and ipsilateral VL. In the remaining two cases, injection sites were situated more rostromedially than that of V18, and partly involved the dorsolateral part of the MVN. In V17 (Fig. 1A), in which the injection site slightly involved the dorsal part of the LVN as well, labeled axon terminals in the VL-VPL were observed mainly ipsilaterally. In V54 (Fig. 1A), in which the center of the injection site was shifted more medially than in the above case V17, and involved the rostrolateral part of the MVN, a small number of labeled fibers and terminals were found in the lateral dorsal nucleus (LD) and anterior pretectal area (APT). Both in V17 and V54, labeled terminals in the PF, LGV, and zona incerta (ZI) were more numerous than those of V18. Fig. 3. Brightfield photomicrograph showing the site of Phaseolus vulgaris leucoagglutinin injection in the superior vestibular nucleus (SuVN), which slightly involved the dorsal part of the lateral vestibular nucleus. The dashed lines represent the demarcation of the nuclei. For abbreviations, see list. Scale bar ⫽ 200 µm.
ties were traced laterally through the VM to enter the VL and VPL. Some of these fibers were seen to ascend further through the VL and VPL to form a moderate number of
Injections in the rostral-to-middle parts of the MVN In V67, the injection site was in the ventromedial part of the MVN. The center of the injection site was in the region close to the genu of the facial nerve (Figs. 1C, 4A) . In this case, many labeled fibers and terminals were observed in the dorsolateral part of the PF, CL-VLc, VL-VPL, and oral part of the VL (VLo). A moderate number of labeled
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Fig. 4. Projection drawings of frontal sections arranged rostrocaudally, showing a site of Phaseolus vulgaris leucoagglutinin injection (shaded area in A) into the middle part of the medial vestibular nucleus (A), and resulting anterograde labeling in the thalamus (B–E). For abbreviations, see list.
terminals were seen in the ZI, dorsal part of the APT (APTD), LGV, and LD (Fig. 4B–E). Some labeled terminals were detected in the Po-VPM, rostral part of the lateral posterior nucleus (LP), mediodorsal thalamic nucleus (MD), and VM. No terminals were identified in the SG and MG. In the dorsolateral part of the PF, many labeled fibers and terminals were seen throughout the rostrocaudal extent, bilaterally with an ipsilateral dominance. In the ipsilateral Po-VPM, a few labeled fibers formed a small patch of axon terminals. A dense plexus of axon terminals was distributed in the CL-VLc, bilaterally with a contralateral dominance. More rostrally, labeled fibers ascending through the VPL were observed to form some small patches of labeled axon terminals mainly in the contralateral VLVPL and VLo. A moderate number of labeled axon terminals were found in the central and lateral parts of the LD. In V21 (Fig. 1D), in which the injection site involved partially the lateral part of the SuVN and LVN as well as the rostral part of the SpVN, a small number of labeled fibers were seen in the contralateral SG. Labeled terminals in the PF were distributed in the lateral middle part of the PF. Labeled terminals in the VL-VPL were seen bilaterally with an ipsilateral dominance. Few labeled terminals were detected in the APTD. In V62 and 64 (Fig. 1C), in which caudal tips of the injection sites slightly
affected the medial part of the SpVN, a few labeled fibers and terminals were found in the SG. In V60 and 61 (Fig. 1D), the injection sites were restricted to the dorsolateral part of the middle MVN. In V21, 60, 61, 62, and V64, a moderate number of labeled fibers and terminals were distributed in the ventrolateral part of contralateral LD. In V71 (Fig. 1D), in which a small injection was confined to the ventrolateral part of the middle MVN and the level of the injection center corresponded to the caudal level of that V67, no terminals were detected in the LD.
Injections in the caudal part of the MVN In this group, labeled fibers and terminals distributed in the thalamus were fewer than those of other groups. In V79, the injection site occupied the medial two-thirds of the caudal half of the MVN except for the caudal tip. Neurons of the prepositus hypoglossal nucleus were not labeled (Figs. 1F, 5A) . In this case, some labeled fibers and terminals were found in the CL-VLc, LD, LGV, and APTD (Fig. 5B–E). Fewer labeled terminals were seen in the PF and ZI. Only a few labeled terminals were detected in the dorsolateral part of the PF, contralaterally. Few labeled axon terminals were seen in the VL-VPL. No labeled terminals were identified in the VM, SG, and MG.
VESTIBULAR PROJECTIONS TO THE THALAMUS
Fig. 5. Projection drawings of frontal sections arranged rostrocaudally, showing a site of Phaseolus vulgaris leucoagglutinin injection (shaded area in A) into the caudal part of the medial vestibular nucleus (A), and resulting anterograde labeling in the thalamus (B–E). For abbreviations, see list.
In V81 (Fig. 1E), in which the injection site was in the medial third of the MVN and the level of the injection corresponded to the rostral quarter of that in the above case V79, few terminals in the thalamus were detected. In the other two cases, the injection site occupied the medial half of the caudal MVN. In V83 (Fig. 1D) and 84 (Fig. 1E), in which injection sites were shifted slightly more rostrally than that of V79, the findings are quite similar to those of V79: no terminals were seen in the PF. In V58 (Fig. 1E), in which the injection site was situated in the dorsolateral part of the caudal MVN and shifted slightly more rostrally than that of V79 and involved partially dorsomedial part of the SpVN, a few labeled terminals were seen in the SG, contralaterally.
Injections in the lateral vestibular nucleus In V94, the injection site was restricted to the lateral third of the rostral half of the LVN and slightly involved the ventral part of the SuVN (Figs. 1A, 6A) . In this case, labeled terminals were found mainly in the PF, CL-VLc, VL-VPL, VL, and additionally in the Po-VPM (Fig. 6B–E). In the PF, a moderate number of labeled axon terminals were seen in the middle part of the lateral PF. A small number of labeled fibers constituted a small patch of axon terminals in the Po-VPM, ipsilaterally. More rostrally, a
moderate number of labeled fibers and terminals were seen in the CL-VLc, ipsilaterally. Small patches of labeled axon terminals were distributed in the VL-VPL and VL, mainly ipsilaterally. In V4 (Fig. 1B) and V50 (Fig. 1A), the injection site occupied the medial half of the rostral LVN, and involved partially the medial part of the MVN. In these cases, labeled terminals were seen mainly in the lateral PF and APTD, ipsilaterally. Labeled terminals in the lateral PF were distributed in the middle and dorsal parts. In the remaining two cases, the injection site occupied the lateral half of the LVN. In V109 (Fig. 1D), the injection was confined to the caudal part of the LVN. The injection site of V110 (Fig. 1C) included the whole rostrocaudal extent of the LVN. Although the caudal tips of injection sites of these cases slightly involved the rostral part of the SpVN, the distribution pattern of labeled fibers and terminals was quite similar to that of V94.
Injections in the spinal vestibular nucleus In V89, the injection site was situated in the lateral two-thirds of the rostral to middle parts of the spinal vestibular nucleus (SpVN), and slightly involved the ros-
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Fig. 6. Projection drawings of frontal sections arranged rostrocaudally, showing a site of Phaseolus vulgaris leucoagglutinin injection (shaded area in A) into the lateral vestibular nucleus (A), and resulting anterograde labeling in the thalamus (B–E). For abbreviations, see list.
tral tip of the external cuneate nucleus and group X, although labeled neurons were confined to the SpVN (Figs. 1E, 7A). In this case, labeled terminals were observed mainly in the posterior nuclear group, VB complex, PF, VL-VPL, VL, and also in the Po-VPM, LGV, ZI, CL, and Pc (Fig. 7B–E). In the posterior nuclear group, many labeled fibers with bouton-like varicosities were traced through the magnocellular nucleus of the MG (MGM), medial part of the Po, and ventral nucleus of the MG (MGV) to constitute dense plexus of axon terminals in the SG, dorsal part of the MG, and inferior border of the MGV, mainly contralaterally. Labeled terminals in the SG were observed to extend to the limitans nucleus (Li), although few labeled fibers and terminals were detected within Li (Figs. 7E, 8A). A dense plexus of labeled axon terminals was observed in the VB complex, especially in the ventral part of VPM and VPL, as well as in the region corresponding to the parvocellular part of the VPL (VPLpc) of Swanson’s atlas (1992), contralaterally (Figs. 7E, 8B, 9). In the PF, many labeled fibers and terminals were distributed in the dorsolateral part, mainly ipsilaterally. More rostrally, small patches of labeled terminals were seen mainly in the contralateral VL-VPL and ipsilateral VL. Only a few labeled terminals were detected in the CL and Pc.
In V88 (Fig. 1E), in which the injection site was shifted slightly more rostrally than that of V89 and was located in the ventrolateral part of the SpVN, labeled terminals in the Po and VB complex were fewer than in V89. In V90, 91, and 97 (Fig. 1E), the injection sites were shifted somewhat more rostrally than in V89 and were restricted to the lateral part of the SpVN, especially to the lateral third (V90), dorsolateral part (V91), and ventrolateral part of the SpVN (V97). In these cases, there is a possibility that an injection site involved the external cuneate nucleus and group X, although the injection centered on the SpVN. In V90, no labeled terminals were seen in LGV. In V91 and 97, labeled terminals in the VL-VPL were fewer than in V89. Few labeled terminals were seen in the LGV.
DISCUSSION The results of the present experiments indicate that the main thalamic targets of individual vestibular nuclei are the lateral PF, CL-VLc, and VL-VPL (mainly transitional zone) from the SuVN; the lateral PF, VL-VPL, CL-VLc, and LD from the rostral-to-middle MVN; the lateral PF, CLVLc, VL-VPL, and VL from the LVN; the caudal VB
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Fig. 7. Projection drawings of frontal sections arranged rostrocaudally, showing a site of Phaseolus vulgaris leucoagglutinin injection (shaded area in A) into the spinal vestibular nucleus (A), and resulting anterograde labeling in the thalamus (B–E). For abbreviations, see list.
Fig. 8. Darkfield photomicrograph showing dense terminal labeling in the suprageniculate nucleus (SG) and the ventral margin of the ventral part of the medial geniculate body (MGV) (A), and the transitional zone between the VB complex and the medial geniculate
body (B) after the Phaseolus vulgaris leucoagglutinin injection into the spinal vestibular nucleus. For abbreviations, see list. Scale bars ⫽ 200 µm in A,B.
complex, SG, lateral PF, VL-VPL, and VL from the SpVN. The present findings demonstrated more extensive vestibulothalamic projections than those of the previous reports
(Fig. 10) . The overall pattern of vestibulothalamic projection seems to be the same across species (Tables 1 and 2, Fig. 10), although the thalamic nuclei in rats are not
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Fig. 9. Brightfield photomicrograph with higher magnification of the labeled fibers and terminals in the transitional zone between the VB complex and the medial geniculate body after the Phaseolus vulgaris leucoagglutinin injection mainly into the SpVN. For abbreviations, see list. Scale bar ⫽ 50 µm.
Fig. 10. Scheme of the vestibular inputs to the thalamus and further projections from the thalamic nuclei. The thickness of the lines and the size of the arrows in the vestibulothalamic connections indicate the density of the projections. For abbreviations, see list.
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TABLE 1. Previous Anatomical Studies on the Vestibulothalamic Projections1 Animals Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Cat Rat Rat Rat Rat Rat Monkey Monkey Monkey Monkey Monkey Monkey
(⫹) (⫹) (⫹)
(⫹) (⫹) Vim
(⫹) LGV Po
(⫹) (⫹) (⫹) VPI CL, Pc
VM MGM (⫹) (⫹)
CL, Pc VM CL Lateral PF MG Lateral PF Vim VPI, VPM VPI, VPLo VPLo VPI, VPLc
Rt CL Lateral MD
Carpenter and Hanna, ’62 Hassler, ’72 Raymond et al., ’74 Raymond et al., ’76 Liedgren et al., ’76b Conde´ and Conde´, ’78 Magnin and Kennedy, ’79 Blum et al., ’79a Kotchabhakdi et al., ’80 Kotchabhakdi et al., ’80 Kotchabhakdi et al., ’80 Kotchabhakdi et al., ’80 Kotchabhakdi et al., ’80 Kotchabhakdi et al., ’80 Maciewicz et al., ’82 Nakano et al., ’85 Nakano et al., ’85 Nagata, ’86 Nagata, ’86 Nagata, ’86 Nagata, ’86 Shiroyama et al., ’95 Hassler, ’48, ’72 Carpenter and Strominger, ’65 Lang et al., ’79 Asanuma et al., ’83 Tracy, ’80 Russchen et al., ’87
Deg Deg Deg ARG HRP HRP HRP HRP* HRP HRP HRP HRP HRP HRP HRP HRP HRP WGA-HRP WGA-HRP WGA-HRP WGA-HRP PHA-L Deg Deg ARG ARG HRP HRP
Cells of origin
SuVN, MVN MVN, SpVN, SuVN MVN, SpVN Caudal SpVN, caudal MVN Caudal MVN, SpVN, group Z SuVN, group Y MVN, SpVN MVN, caudal SpVN, group Z LVN, SuVN MVN All vestibular nuclei Caudal MVN MVN, SuVN SuVN, LVN SpVN MVN, SuVN, SpVN
SuVN, LVN, MVN MVN, SpVN, LVN
abbreviations, see list. 2iLa, intralaminar nuclei. 3Deg, degeneration; ARG, autoradiography; HRP, horseradish peroxidase; HRP*, HRP ⫹ electrophysiology; WGA-HRP, wheat germ agglutinin-HRP; PHA-L, Phaseolus vulgaris leucoagglutinin; VPLo, oral part of the VPL; VPLc, caudal part of the VPL.
TABLE 2. Previous Electrophysiological Studies on the Vestibulothalamic Projections1 Animals
Cat Cat Cat Cat Cat Cat Cat Cat
VPL-MG MGM MGM Dorsomedian VPL, middle VL MG, VPL, VL Po MGM MGM
Cat Cat Cat Cat Cat
Rt, LGV VPL-Po, CL, Po, VPL-Po Most rostral Po, VPL, VPM MGM CM, CL, VL, VPL, VPM, VM, LGV, LP Dorsal VPI Dorsal VPI, VPL MGM, SG, Po, VPLc, VPLo, Rt, ZI Caudal VPLc, Vim Dorsal and oral VPI MGV, Vim
Monkey Monkey Monkey Monkey Monkey Man 1For
Authors Mickel and Ades, ’54 Spiegel et al., ’65 Wepsic, ’66 Sans et al., ’70 Copack et al., ’72 Liedgren and Rubin, ’76 Abraham et al., ’77 Roucoux-Hanus and BoisacqSchepens, ’77 Magnin and Putkonen, ’78 Blum and Gilman, ’79 Blum et al., ’79a Blum et al., ’79b Matsuo et al., ’94 Deecke et al., ’74 Bu¨ttner and Henn, ’76 Liedgren et al., ’76a Liedgren and Schwarz, ’76 Deecke et al., ’77 Hawrylyshyn et al., ’78
abbreviations, see list.
highly differentiated as in primates. Our findings also suggest existence of vestibulothalamostriatal connections in addition to vestibulothalamocortical connections.
Projection to the thalamic posterior group Only a few anatomical studies have described vestibular inputs to the thalamic posterior nuclear group, in contrast to many electrophysiologic studies (see Tables 1 and 2). The vestibular input to the MGM was initially described by the degeneration studies of Carpenter and Hanna (1962) and Hassler (1972), which were contradicted by the autoradiographic study of Lang et al. (1979) but confirmed by HRP studies of Kotchabhakdi et al. (1980) and Nagata (1986). Our experiments demonstrated strong projections from the SpVN to the SG, the dorsal part of the MG and to the
inferior border of the ventral nucleus of the MG (MGV) (Figs. 7–E, 8–E). The heaviest projection was observed in the SG, although such a strong projection was not described in the previous studies. Labeled terminals in the MGM were restricted to its dorsal region, as well as numerous fibers passing through the whole extent of the nucleus. Dense terminal labeling was also seen in the inferior border of the MGV. In the human, the vestibular responses were elicited during stimulation in MGV (Hawrylyshyn et al., 1978). This nucleus projects to the auditory cortex (Jones, 1985). In the present findings, the vestibuloMGM projection was fewer than reported by Kotchabhakdi et al. (1980) and Nagata (1986). This discrepancy might be attributable to the extension of the injection site and to the uptake of HRP by passing fibers. The SG receives afferents from the intermediate or deep layer of the superior colliculus and the interstitial nucleus of the brachium of the inferior colliculus, and projects to the insular cortex (see Jones, 1985), primary auditory cortex, auditory association cortex of the temporal lobe, and the frontal eye field (FEF) (Kurokawa et al., 1990). The vestibular projection to the insular cortex was proposed by some authors (Gru¨sser et al., 1990a,b; Guldin et al., 1992; Akbarian et al., 1992). The SG also projects to area 7 (Kadson and Jacobson, 1978; Asanuma et al., 1985; Faugier-Grimaud and Ventre, 1989), which is related to visual attention and visuomotor behavior (Leichnetz and Goldberg, 1988; Pierrot-Deseilligny et al., 1995), and to the FEF (Huerta et al., 1986; Kurokawa et al., 1990). Vestibular activity was recorded in the FEF (Fukushima and Fukushima, 1997), and in the visual tracking neurons of area 7 (Kawano et al., 1980; Kawano and Sasaki, 1984; Leinonen et al., 1980). Our data suggest the vestibular projections to the insular and parietal cortices, FEF, and the auditory association cortex of temporal lobe could be relayed by means of the SG.
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Projection to the PF, CL, and Pc The lateral part of the PF received inputs mainly from the SuVN, rostral to middle MVN, and SpVN (Figs. 2E, 4E, 7D). These projections were discussed in our previous report (Shiroyama et al., 1995). In the monkey, the PFcentromedian nuclear complex (PF-CeM) also receive vestibular afferents (Matsuyama et al., personal communication). The CL and Pc receive vestibular inputs mainly from the MVN (Nakano et al., 1985), and contralateral SuVN and group Y (Kotchabhakdi et al., 1980). Our findings confirmed the CL and Pc projections and demonstrated more numerous vestibular terminations in the lateral CL and Pc from the SuVN and the rostral-to-middle MVN. The intralaminar nuclei are known to be involved in gaze control (Schlag and Schlag-Rey, 1984), and thalamic lesions involving these nuclei produced impairment of memory-guided saccades (Gaymard et al., 1994). The CL receives inputs from the superior colliculus, cerebral cortex, cerebellar nuclei, pretectal area, other brainstem areas, and spinal cord, in addition to vestibular input (for reviews see Jones, 1985; Macchi and Bentivoglio, 1986) and projects to the FEF (Barbas and Mesulam, 1981) and area 7 (Faugier-Grimaud and Ventre, 1989). Both FEF and area 7 receive thalamic inputs from the CL, SG, mediodorsal nucleus (MD), and the lateroposterior nucleus (LP, corresponding to the pulvinar in primates) (see Leichnetz and Goldberg, 1988). All of these nuclei receive the vestibular afferents as indicated in our cases. The FEF is thought to be a trigger area for the brainstem saccade generator, whereas neurons in area 7 discharge before visually guided saccades (Leichnetz and Goldberg, 1988; PierrotDeseilligny et al., 1995).
Projection to the caudal part of VB complex The VB complex projection has been reported to receive vestibular afferents by using the electrophysiologic method (Mickel and Ades, 1954; Sans et al., 1970; Liedgren et al., 1976a; Bu¨ttner and Henn, 1976; Blum and Gilman, 1979; Blum et al., 1979a) and anatomical method (Carpenter and Strominger, 1965; Lang et al., 1979; Kotchabhakdi et al., 1980; Tracy et al., 1980). However, the detail of this projection is still controversial as demonstrated in Tables 1 and 2. In the present study, the SpVN projected strongly to the border region between the caudal VB complex and the rostral MG (Figs. 7D, 8B, 9). Dense plexus of labeled terminals were observed in the ventral half of the VPM, VPL, and VPLc of Swanson’ s atlas (1992), mainly contralaterally. Additionally a small number of fibers arising from the rostral-to-middle MVN were seen to terminate in the border region between the VPM and Po, mainly ipsilaterally (Fig. 4E). These results confirmed the strong vestibular projection to the caudal part of the VB complex. The convergence of vestibular input was reported in the VPI with proprioceptive inputs from muscles and joints in monkeys (Deecke et al., 1977). In the monkey, the VPI receives vestibular afferents mainly from the caudal SpVN (Matsuyama et al., personal communication), and projects to the cerebral cortex, including area 2V (Deecke et al., 1974), parietoinsular cortex (Akbarian et al., 1992), and area 7 (Faugier-Grimaud and Ventre, 1989). In the cat, the caudal VB complex projects to the parietal vestibular cortex (Blum et al., 1979a). Although it is not clear whether the caudal part of VB complex receiving vestibu-
lar inputs in cats corresponds to the monkey’s VPI or not, our data suggest VPI projection to these parietal cortical areas.
Projection to the nucleus ventralis intermedius, VL, and VM The nucleus ventralis intermedius (Vim, transitional zone between VL-VPL) received massive inputs mainly from the SuVN (Fig. 2C), the rostral-to-middle parts of MVN (Fig. 4C), and the SpVN (Fig. 7C), mainly contralaterally, and sparse inputs from the caudal MVN (Fig. 5B) and LVN (Fig. 6B). These terminals were distributed in patch-like manner in Vim as shown in previous studies (Liedgren and Schwarz, 1976; Lang et al., 1979; Kotchabhakdi et al., 1980). The Vim delineation is inconsistent among investigators. According to Nakano et al. (1992b), the Vim corresponds to the transitional zone between the oral and caudal part of VPL, where inputs overlap from the cerebellar, dorsal columnar and vestibular nuclei, and from the spinothalamic tract. Vestibular inputs to the Vim were originally suggested by Hassler (1948) who used the degeneration method. Consequently, this projection was demonstrated by using axonal transport techniques and electrophysiologic techniques (see Tables 1 and 2). However, there is no agreement concerning the origin of this projection, such as the SuVN, LVN, and MVN (Lang et al., 1979), the LVN (Maciewicz et al., 1982), all the nuclei of the VN (Kotchabhakdi et al., 1980). Our findings are nearly consistent with those of Kotchabhakdi et al. (1980), except for the caudal MVN, which were not observed in our cases. Area 3a responds to vestibular activities (Sans et al., ¨ dkvist 1970; Boisacq-Schepens and Roucoux-Hanus, 1972; O et al., 1974), and the Vim projects to area 3a (Liedgren et al., 1976b; Nakano et al., 1992b). Area 3a seems to receive vestibular inputs by means of the Vim. According to Hassler (1972), the lateral and medial parts of the Vim appear to receive muscular and vestibular inputs, respectively, and project to area 3a. The VA-VL and VM receive vestibular afferents (Hassler, 1972; Raymond et al., 1974; Conde´ and Conde´, 1978; Kotchabhakdi et al., 1980; Nakano et al., 1985). Small patches of labeled terminals were observed in the rostrocaudal extent of the VL, mainly ipsilaterally (Figs. 2B, 6B, 7B). Labeled fibers and terminals were seen in the rostral VL corresponding to the cat’s VA-VL complex. The caudal VL adjacent to the CL received inputs mainly from the SuVN and the rostral-to-middle MVN. The border region between the VL and CL receives afferents from the contralateral SuVN and the MVN (Conde´ and Conde´, 1978). In our cases, this pathway was seen bilaterally, and the projection from the SuVN was dominant ipsilaterally (Fig. 2D). The VA-VL complex receives afferents from the MVN (Nakano et al., 1985), and this finding was confirmed in the present cases (Fig. 4B). Because the VA-VL complex projects to the motor and premotor areas (Nakano et al., 1992a), these areas might receive vestibular information. The VM receives sparse vestibular afferents from contralateral MVN and SpVN (Kotchabhakdi et al., 1980) or all vestibular nuclei, but mainly bilateral MVN and SpVN (Nakano et al., 1985). In the present investigation, a few fibers from the SuVN and the rostral-to-middle MVN were seen to terminate in the lateral part of VM, bilaterally. The lateral part of the VM, but not the dorsal part, is more
VESTIBULAR PROJECTIONS TO THE THALAMUS directly related to the cortical area receiving the VL projection (Arbuthnott et al., 1990).
Projection to the other thalamic nuclei Other thalamic nuclei receiving vestibular afferents are the MD (Russchen et al., 1987), LGV (Magnin and Kennedy, 1979), the thalamic reticular nucleus (Rt) (Carpenter and Strominger, 1965; Liedgren et al., 1976a; Magnin and Putkonen, 1978), and the ZI (Liedgren et al., 1976a). The present results confirmed these projections, except for the Rt, and further demonstrated a projection to the LD, which had not been reported previously. Ascending fibers from the MVN terminated throughout LD, mainly in its ventrolateral part, contralaterally (Figs. 4C, 5B). The LD projects to the limbic and visual cortices and area 7 (Asanuma et al., 1985; Van Groen and Wyss, 1992). The dorsolateral LD was suggested to be involved in the visual system (Thompson and Robertson, 1987), whereas the ventral LD projects to area 7 (Asanuma et al., 1985). The lateral MD received vestibular afferents as indicated by Russchen et al. (1987). In the present study, a few terminals were observed contralaterally in this part arising mainly from the rostral part of the MVN. The lateral MD projects to the FEF and affects gaze control (Huerta et al., 1986). The LGV receives vestibular inputs from the MVN, SpVN, and SuVN (Magnin and Kennedy, 1979). In our findings, the LGV receives inputs contralaterally from the rostral to middle MVN (Fig. 4E) and ipsilaterally from the caudal MVN and SpVN (Figs. 5E, 7D,E). The caudal MVN and SpVN project mainly to the medial LGV. Fibers from SuVN were sparse (Fig. 2E). The LGV projects to the CL, and the vestibulo-LGV-CL connections were reported by Magnin and Kennedy (1979). The vestibuloLGV-intralaminar pathway suggests that vestibular and oculomotor influences could participate in early levels of motor processing involving either the pyramidal or the extrapyramidal system (Magnin and Kennedy, 1979). The ZI receives afferents from the somatosensory cortex, the spinal trigeminal nucleus, the dorsal column nuclei, and the deep cerebellar nuclei and plays a role in the production of orienting movements (Kim et al., 1992). Neurons of Forel’s field H receive afferents from the superior colliculus and seem to be involved in control of the vertical component of orienting head movements (Isa and Naito, 1995). In the present findings, vestibular afferents to the ZI and Forel’s filed H were demonstrated.
Functional implication As already mentioned, the lateral PF receives vestibular afferents, and this portion in rats seems to correspond to the centromedian nucleus (CeM) in primates (Jones, 1985). The CeM receives multiple sensorimotor information including vestibular information, and appears to exert its influences on the striatum. Recent studies that used PET have reported vestibular activation in the human putamen (Bottini et al., 1994, 1995), although only early electrophysiologic studies recorded vestibular responses in the caudate nucleus in animals (Spiegel et al., 1965; Copack et al., 1972; Liedgren and Schwarz, 1976), and its connection was suggested relaying through the MGM (Potegal et al., 1971) and CeM (Spiegel et al., 1965). Dopaminergic receptor in the striatum seems to be involved in the vestibular compensation in rats (Giardino et al., 1996). Our data suggests strong vestibular connection to the striatum relaying PF-CeM and CL.
329 The basal ganglia are known to be involved in motor, cognitive, and emotional behaviors (for review see Nakano et al., 1995), and also implicated in saccadic eye movement (Hikosaka and Wurtz, 1989). Vermersch et al. (1996) reported that the putamen plays a role in the control of intentional, internally triggered saccades, such as memoryguided saccades. According to behavioral studies, animals are able to compute the distance and direction of their movements through space, by using vestibular information. The basal ganglia seem to use vestibular inputs for postural control and spatial tasks. Vestibular cortical areas were identified by means of evoked potential studies in area 2V (located in the anterior parietal lobe), area 3aV, and the parietoinsular vestibular cortex (PIVC) or retroinsular area in the monkey (Bu¨ttner ¨ dkvist et al., 1974; Gru¨sser et al., and Bu¨ttner, 1978; O 1982, 1990a,b; Fredrickson and Rubin, 1986; Guldin and Gru¨sser, 1987). Many of the neurons in PIVC respond not only to vestibular and optokinetic stimulation, but also to proprioceptive stimuli from muscle or joint mechanoreceptors especially in the neck region (Guldin et al., 1992). Area 7a was also found to respond to vestibular stimulation (Leinonen et al., 1980; Gru¨sser et al., 1982; Kawano and Sasaki, 1984). This area is involved in spatial attention and integration (Andersen, 1987), as well as the control of visual memory-guided saccades (Andersen et al., 1990b). According to Guldin et al. (1992), the PIVC, area 3aV and area 2V, are reciprocally interconnected for processing vestibular information about head-in-space movement. The vestibular nuclei integrate visual and vestibular signals (Precht, 1975). The PIVC receives visuomotor signals by means of thalamic vestibular territories, or by means of the parietotemporal association cortex (T3) and area 19. The PIVC connects with FEF, area T3, area 7, granular insular cortex, cingulate cortex, and the ventral part of premotor area, and participates in the cortical network monitoring head and body movements in space (Guldin et al., 1992). The integrated multimodal signal might be updated by a complex corticocortical input to PIVC. The PIVC seems to be a cortical area involved in the perception of head-in-space movements. On the basis of our data, the PIVC appears to receive vestibular afferents relaying in the SG, MG, and VB complex. Area 7a projects both to the prefrontal cortex (Cavada and Goldman-Rakic, 1989; Andersen et al., 1990a) and the parietal eye field, which is located in the lateral intraparietal area, and triggers visually guided saccades in the monkey. Area 7a seems to be less crucial for vestibular inputs than for visual inputs. The vestibular cortex, located in the posterior part of the superior temporal gyrus (Andersen et al., 1990a), could be involved at the integration stage in memory-guided saccades with vestibular input. The posterior part of the superior temporal gyrus and area 7 appear to receive vestibular afferents by means of MG, SG, and VB. The CL also relays vestibular input to area 7. The dorsolateral part of the prefrontal cortex is involved in the control of the spatial aspect of working memory (Funahashi et al., 1993). Finally, the prefrontal cortex appears to be the only common cortical area involved during memory-guided saccades with visual input and those with vestibular input (Pierrot-Deseilligny et al., 1995). The prefrontal cortex is involved not only in visual representation of space (Goldman-Rakic, 1987), but also in vestibular representation of the displacement and orientation of the body in space (Israe¨l et al., 1995).
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The intralaminar nuclei seem to be involved in the processing of eye position determined by using nonvisual information (Gaymard et al., 1994). Of these nuclei, the CL is the major target of vestibular afferents, as indicated in the present findings, and connects to the FEF and area 7a. As mentioned above, the CL receives polymodal afferents, and projects to the striatum (Jones and Leavitt, 1974; Nakano et al., 1990), parietal cortex (Mergner et al., 1981; Asanuma et al., 1985), primary somatosensory area (Jones et al., 1979), motor area (Jones et al., 1979; Donoghue and Parham, 1983; Nakano et al., 1993), and supplementary motor area (Nakano et al., 1993). Intralaminar nuclei seem to play a role in the higher central activation mechanisms and in the finalized sensory-motor behavior. Vestibular activity converges with cerebellar input in the oral part of the VPL in monkeys and is relayed to the motor area (Asanuma et al., 1983). Our findings support the vestibulomotor area projection by means of VA-VL, and CL in rats. As the motor area receives area 3a afferents (Porter, 1991), vestibular information also could be relayed to the motor area by means of area 3a, as well as motor thalamic nuclei and CL. The vestibular inputs appear to participate in movement and postural controls in the basal ganglia and motor-related cortical areas. Although our data suggest vestibulothalamocortical projections from distinct vestibular nuclei, the functional difference between information from distinct vestibular nuclei remains to be elucidated.
LITERATURE CITED Abraham L, Copack PB, Gilman S. 1977. Brainstem pathways for vestibular projections to cerebral cortex in the cat. Exp Neurol 55:436–448. Akbarian S, Gru¨sser OJ, Guldin WO. 1992. Thalamic connections of the vestibular cortical fields in the squirrel monkey(Saimiri sciureus). J Comp Neurol 326:423–441. Andersen RA. 1987. Inferior parietal lobule function in spatial perception and visuomotor integration. In: Mountcastle VB, Plum F, Geiger SR, editors. Handbook of physiology, Sect 1. Bethesda, MD: American Physiological Society. p 483–518. Andersen RA, Asanuma C, Essick G, Siegel RM. 1990a. Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule. J Comp Neurol 296:65–113. Andersen RA, Bracewell RM, Barash S, Gnadt JW, Fogassi L. 1990b. Eye position effects on visual, memory, and saccade related activity in areas LIP and 7a of macaque. J Neurosci 10:1176–1196. Arbuthnott GW, MacLeod NK, Maxwell DJ, Wright AK. 1990. Distribution and synaptic contacts of the cortical terminals arising from neurons in the rat ventromedial thalamic nucleus. Neuroscience 38:47–60. Asanuma C, Thach WT, Jones EG. 1983. Distribution of cerebellar terminations and their relation to other afferent terminations in the ventral lateral thalamic region of the monkey. Brain Res Rev 5:237–265. Asanuma C, Andersen RA, Cowan WM. 1985. The thalamic relations of the caudal inferior parietal lobule and the lateral prefrontal cortex in monkeys: divergent cortical projections from cell clusters in the medial pulvinar nucleus. J Comp Neurol 241:357–381. Barbas H, Mesulam M-M. 1981. Organization of afferent input to subdivisions of area 8 in the rhesus monkey. J Comp Neurol 200:407–431. Blum PS, Gilman S. 1979. Vestibular, somatosensory, and auditory input to the thalamus of the cat. Exp Neurol 65:343–354. Blum PS, Day MJ, Carpenter MB, Gilman S. 1979a. Thalamic components of the ascending vestibular system. Exp Neurol 64:587–603. Blum PS, Abraham LD, Gilman S. 1979b. Vestibular, auditory, and somatic input to the posterior thalamus of the cat. Exp Brain Res 34:1–9. Boisacq-Schepens N, Roucoux-Hanus M. 1972. Motor cortex vestibular responses in the chloralosed cat. Exp Brain Res 14:539–549. Bottini G, Sterzi R, Paulesu E, Vallar G, Cappa SF, Erminio F, Passingham RE, Frith CD, Frackowiak RSJ. 1994. Identification of the central vestibular projections in man: a positron emission tomography activation study. Exp Brain Res 99:164–169.
Bottini G, Paulesu E, Sterzi R, Warburton E, Wise RJS, Vallar G, Frackowiak RSJ, Frith CD. 1995. Modulation of conscious experience by peripheral sensory stimuli. Nature 376:778–781. Brodal A, Brodal P. 1985. Observations on the secondary vestibulocerebellar projections in the macaque monkey. Exp Brain Res 58:62–74. Brodal A, Pompeiano O. 1957. The vestibular nuclei in the cat. J Anat 91:438–454. Bu¨ttner U, Bu¨ttner UW. 1978. Parietal cortex activity in the alert monkey during natural vestibular and optokinetic stimulation. Brain Res 153:392–397. Bu¨ttner U, Henn V. 1976. Thalamic unit activity in the alert monkey during natural vestibular stimulation. Brain Res 103:127–132. Bu¨ttner-Ennever JA, Bu¨ttner U. 1988. The reticular formation. In: Bu¨ttnerEnnever JA, editor. Neuroanatomy of the oculomotor system. Amsterdam: Elsevier Science Publishers BN (Biomedical Division). p 119–176. Carleton SC, Carpenter MB. 1983. Afferent and efferent connections of the medial, inferior and lateral vestibular nuclei in the cat and monkey. Brain Res 278:29–51. Carpenter MB, Cowie RJ. 1985. Connections and oculomotor projections of the superior vestibular nucleus and cell group ‘y.’ Brain Res 336:265– 287. Carpenter MB, Hanna G. 1962. Lesions of the medial longitudinal fasciculus in the cat. Am J Anat 110:307–331. Carpenter MB, Strominger NL. 1965. The medial longitudinal fasciculus and disturbances of conjugate horizontal eye movements in the monkey. J Comp Neurol 125:41–66. Cavada C, Godman-Rakic PS. 1989. Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe. J Comp Neurol 287:422–445. Cheron G, Escudero M, Godaux E. 1996. Discharge properties of brain stem neurons projecting to the flocculus in the alert cat: I. Medial vestibular nucleus. J Neurophysiol 76:1759–1774. Conde´ F, Conde´ H. 1978. Thalamic projections of the vestibular nuclei in the cat as revealed by retrograde transport of horseradish peroxidase. Neurosci Lett 9:141–146. Copack P, Dafny N, Gilman S. 1972. Neurophysiological evidence of vestibular projections to thalamus, basal ganglia, and cerebral cortex. In: Frigyesi T, Rinvic E, Yahr MD, editor. Corticothalamic projections and sensorimotor activities. New York: Raven Press. p 309–339. Deecke L, Schwarz DW, Fredrickson JM. 1974. Nucleus ventroposterior inferior (VPI) as the vestibular thalamic relay in the rhesus monkey: I. Field potential investigation. Exp Brain Res 20:88–100. Deecke L, Schwarz DW, Fredrickson JM. 1977. Vestibular responses in the rhesus monkey ventroposterior thalamus: II. Vestibulo-proprioceptive convergence at thalamic neurons. Exp Brain Res 30:219–232. Donoghue JP, Parham C. 1983. Afferent connections of the lateral agranular field of the rat motor cortex. J Comp Neurol 217:390–404. Faugier-Grimaud S, Ventre J. 1989. Anatomic connections of inferior parietal cortex (area 7) with subcortical structures related to vestibuloocular function in a monkey (Macaca fascicularis). J Comp Neurol 280:1–14. Fredrickson JM, Rubin AM. 1986. Vestibular cortex. In: Jones EG, Peters A, editor. Cerebral cortex, Vol 5. Sensory-motor areas and aspects of cortical connectivity. New York and London: Plenum Press. p 99–111. Fukushima K, Fukushima J. 1997. Vestibular input to the frontal eye field and its close vicinity in alert monkeys. Neurosci Res suppl 21:S185. Funahashi S, Bruce CJ, Goldman-Rakic PS. 1993. Dorsolateral prefrontal legions and oculomotor delayed-response performance: evidence for mnemonic ‘‘scotomas.’’ J Neurosci 13:1479–1497. Gaymard B, Rivaud S, Pierrot-Deseilligny C. 1994. Impairment of extraretinal eye position signals after central thalamic legions in humans. Exp Brain Res 102:1–9. Gerfen C, Sawchenko P. 1984. An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, there axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L). Brain Res 290:219–238. Gerfen CR, Sawchenko PE, Carlsen J. 1989. The PHA-L anterograde axonal tracing method. In: Heimer L, Zba´orszky L, editors. Neuroanatomical tract-tracing methods 2. New York: Plenum Press. p 19–47. Giardino L, Zanni M, Pignataro O. 1996. DA1 and DA2 receptor regulation in the striatum of young and old rats after peripheral vestibular lesion. Brain Res 736:111–117.
VESTIBULAR PROJECTIONS TO THE THALAMUS Goldman-Rakic PS. 1987. Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Mountcastle VB, Plum F, Geiser SR, editors. Handbook of physiology, Sect 1, Vol 5. Bethesda, MD: American Physiological Society. p 373–417. Gru¨sser OJ, Pause M, Schreiter U. 1982. Neuronal responses in the parieto-insular vestibular cortex of alert Java monkeys (Macaca fascicularis). In: Roucoux A, Crommelinck M, editors. Physiological and pathological aspects of eye movements. The Hague: W Junk Publishers. p 251–270. Gru¨sser OJ, Pause M, Schreiter U. 1990a. Localization and responses of neurons in the parieto-insular vestibular cortex of awake monkeys (Macaca fascicularis). J Physiol 430:537–557. Gru¨sser OJ, Pause M, Schreiter U. 1990b. Vestibular neurons in the parieto-insular cortex of monkeys (Macaca fascicularis): visual and neck receptor responses. J Physiol 430:559–583. Guldin WO, Gru¨sser OJ. 1987. Single unit responses in the vestibular cortex of squirrel monkeys. Soc Neurosci Abstr 13:1224. Guldin WO, Akbarian S, Gru¨sser OJ. 1992. Cortico-cortical connections and cytoarchitectonics of the primate vestibular cortex: a study in squirrel monkeys (Saimiri sciureus). J Comp Neurol 326:375–401. Hassler R. 1948. Forels Haubenfaszikel als vestibula¨re Empfindungsbahn mit Bemerkungen u¨ber einige andere sekundra¨e Bahnen des Vestibularis und Trigeminus. Arch Psychiat Nervenkr 180:23–53. Hassler R. 1972. Hexapartition of inputs as a primary role of the thalamus. In: Frigyesi T, editor. Corticothalamic projections and sensorimotor activities. New York: Raven Press. p 551–579. Hawrylyshyn PA, Rubin AM, Tasker RR, Organ LW, Fredrickson JM. 1978. Vestibulothalamic projections in man-a sixth primary sensory pathway. J Neurophysiol 41:394–401. Hikosaka O, Wurtz RH. 1989. The basal ganglia. In: Wurtz RZ, Goldberg ME, editors. The neurobiology of saccade eye movements. Amsterdam: Elsevier Science Publishers BV (Biomedical Division). p 257–281. Huerta MF, Krubitzer LA, Kaas JH. 1986. Frontal eye field as defined by intracortical microstimulation in squirrel monkeys, owl monkeys, and macaque monkeys: I. subcortical connections. J Comp Neurol 253:415– 439. Isa T, Naito K. 1995. Activity of neurons in the medial pontomedullary reticular formation during orienting movements in alert head-free cats. J Neurophysiol 74:73–95. Israe¨l I, Rivaud S, Gaymard B, Berthoz A, Pierrot-Deseilligny C. 1995. Cortical control of vestibular-guided saccades in man. Brain 118:1169– 1183. Jones EG. 1985. The thalamus. New York and London: Plenum Press. Jones EG, Leavitt RY. 1974. Retrograde axonal transport and the demonstration of non-specific projections to the cerebral cortex and striatum from thalamic intralaminar nuclei in the rat, cat and monkey. J Comp Neurol 154:349–378. Jones EG, Wise SP, Coulter JD. 1979. Differential thalamic relationships of sensory-motor and parietal cortical fields in monkeys. J Comp Neurol 183:833–882. Kadson DL, Jacobson S. 1978. The thalamic afferents to the inferior parietal lobule of the rhesus monkey. J Comp Neurol 177:685–706. Kawano K, Sasaki M. 1984. Response properties of neurons in posterior parietal cortex of monkey during visual-vestibular stimulation: II. Optokinetic neurons. J Neurophysiol 51:352–360. Kawano K, Sasaki M, Yamashita M. 1980. Vestibular input to visual tracking neurons in the posterior parietal association cortex of the monkey. Neurosci Lett 17:55–60. Kim U, Gregory E, Hall WC. 1992. Pathway from the zona incerta to the superior colliculus in the rat. J Comp Neurol 321:555–575. Kotchabhakdi N, Rinvik E, Walberg F, Yingchareon K. 1980. The vestibulothalamic projections in the cat studied by retrograde axonal transport of horseradish peroxidase. Exp Brain Res 40:405–418. Kurokawa T, Yoshida K, Yamamoto T, Oka H. 1990. Frontal cortical projections from the suprageniculate nucleus in the rat, as demonstrated with the PHA-L method. Neurosci Lett 120:259–262. Lang W, Bu¨ttner EJ, Bu¨ttner U. 1979. Vestibular projections to the monkey thalamus: an autoradiographic study Brain Res 177:3–17. Leichnetz GR, Goldberg ME. 1988. Higher centers concerned with eye movement and visual attention: cerebral cortex and thalamus. In: Bu¨ttner-Ennever JA, editor. Neuroanatomy of the oculomotor system. Amsterdam: Elsevier Science Publishers BV (Biomedical Devision). p 365–429.
331 Leigh RJ, Brandt T. 1993. A reevaluation of the vestibulo-ocular reflex: new ideas of its purpose, properties, neural substrate, and disorders. Neurology 43:1288–1295. Leinonen L, Hyva¨rinen J, Sovija¨rvi ARA. 1980. Functional properties of neurons in the temporo-parietal association cortex of awake monkey. Exp Brain Res 39:203–215. Liedgren S, Rubin AM. 1976. Vestibulo-thalamic projections studied with antidromic technique in the cat. Acta Otolaryngol 82:379–387. Liedgren SR, Schwarz DW. 1976. Vestibular evoked potentials in thalamus and basal ganglia of the squirrel monkey (Saimiri sciureus). Acta Otolaryngol 81:73–82. Liedgren SR, Milne AC, Schwarz DW, Tomlinson RD. 1976a. Representation of vestibular afferents in somatosensory thalamic nuclei of the squirrel monkey (Saimiri sciureus). J Neurophysiol 39:601–612. ¨ dkvist LM. 1976b. Projection of Liedgren SR, Kristensson K, Larsby B, O thalamic neurons to cat primary vestibular cortical fields studied by means of retrograde axonal transport of horseradish peroxidase. Exp Brain Res 24:237–243. Macchi G, Bentivoglio N. 1986. The thalamic intralaminar nuclei and the cerebral cortex. In: Jones EG, Peters A, editors. Cerebral cortex, Vol 5. Sensory-motor areas and aspects of cortical connectivity. New York: Plenum Press. p 355–401. Maciewicz R, Phipps BS, Bry J, Highstein SM. 1982. The vestibulothalamic pathway: contribution of the ascending tract of Deiters. Brain Res 252:1–11. Magnin M, Kennedy H. 1979. Anatomical evidence of a third ascending vestibular pathway involving the ventral lateral geniculate nucleus and the intralaminar nuclei of the cat. Brain Res 171:523–529. Magnin M, Putkonen PT. 1978. A new vestibular thalamic area: electrophysiological study of the thalamic reticular nucleus and of the ventral lateral geniculate complex of the cat. Exp Brain Res 32:91–104. Matsuo S, Hosogi M, Nakao S. 1994. Ascending projections of posterior canal-activated excitatory and inhibitory secondary vestibular neurons to the mesodiencephalon in cats. Exp Brain Res 100:7–17. McCrea RA, Strassman A, May E, Highstein SM. 1987a. Anatomical and physiological characteristics of vestibular neurons mediating the horizontal vestibulo-ocular reflex of the squirrel monkey. J Comp Neurol 264:547–570. McCrea RA, Strassman A, Highstein SM. 1987b. Anatomical and physiological characteristics of vestibular neurons mediating the vertical vestibuloocular reflexes of the squirrel monkey. J Comp Neurol 264:571–594. Mergner T, Deecke L, Wagner HJ. 1981. Vestibulo-thalamic projection to the anterior suprasylvian cortex of the cat. Exp Brain Res 44:455–458. Mickel WA, Ades HW. 1954. Rostral projection pathway of the vestibular system. Am J Physiol 176:243–246. Nagata S. 1986. The vestibulothalamic connections in the rat: a morphological analysis using wheat germ agglutinin-horseradish peroxidase. Brain Res 376:57–70. Nakano K, Kohno M, Hasegawa Y, Tokushige A. 1985. Cortical and brain stem afferents to the ventral thalamic nuclei of the cat demonstrated by retrograde axonal transport of horseradish peroxidase. J Comp Neurol 231:102–120. Nakano K, Hasegawa Y, Tokushige A, Nakagawa S, Kayahara T, Mizuno N. 1990. Topographical projections from the thalamus, subthalamic nucleus and pedunculopontine tegmental nucleus to the striatum in Japanese monkey, Macaca fuscata. Brain Res 537:54–68. Nakano K, Tokushige A, Kohno M, Hasegawa Y, Kayahara T, Sasaki K. 1992a. an autoradiographic study of cortical projections from motor thalamic nuclei in the macaque monkey. Neurosci Res 13:119–137. Nakano K, Kayahara T, Yasui Y, Kuwabara H. 1992b. Thalamic region projecting to area 3a: an autoradiographic study in the monkey. Neuroscience 18:89–100. Nakano K, Hasegawa Y, Kayahara T, Tokushige A, Kuga Y. 1993. Cortical connections of the motor thalamic nuclei in the Japanese monkey, Macaca fuscata. Stereotact Funct Neurosurg 60:42–61. Nakano K, Kayahara T, Ushiro H, Hasegawa Y. 1995. Some aspects of basal ganglia-thalamocortical circuitry and descending outputs of the basal ganglia. In: Segawa M, Nomura Y, editors. Age-related dopaminedependent disorders. Basel: S Karger. p 134–146. ¨ dkvist LM, Schwarz DW, Fredrickson JM, Hassler R. 1974. Projection of O the vestibular nerve to the area 3a arm field in the squirrel monkey (Saimiri sciureus). Exp Brain Res 21:97–105. Paxinos G, Watson C. 1986. The rat brain in stereotaxic coordinates, 2nd Ed. Sydney: Academic Press.
332 Pierrot-Deseilligny C, Rivaud S, Gaymard B, Mru¨i R, Vermersch A-I. 1995. Cortical control of saccades. Ann Neurol 37:557–567. Porter LL. 1991. Patterns of connectivity in the cat sensory-motor cortex: a light and electron microscope analysis of the projection arising from area 3a. J Comp Neurol 312:404–414. Potegal M, Copack P, deJong JMBV, Krauthamer G, Gilman S. 1971. Vestibular input to the caudate nucleus. Exp Neurol 32:448–465. Precht W. 1975. Vestibular system. In: Guyton AC, Hunt CC, editors. MTP international review of sciences neurophysiology physiology, Series one. London, Baltimore: Butterworths Univ Park Press. p 82–149. Raymond J, Sans A, Marty R. 1974. Thalamic projections of the vestibular nuclei: a histological study in the cat. Exp Brain Res 20:273–283. Raymond J, Dememes D, Marty R. 1976. Pathways and ascending vestibular projections emanating from primary nuclei: radioautographic study. Brain Res 111:1–12. Roucoux-Hanus M, Boisacq-Schepens N. 1977. Ascending vestibular projections: further results at cortical and thalamic levels in the cat. Exp Brain Res 29:283–292. Russchen FT, Amaral DG, Price JL. 1987. The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis. J Comp Neurol 256:175–210. Sans A, Raymond J, Marty R. 1970. Thalamic and cortical responses to electric stimulation of the vestibular nerve in the cat. Exp Brain Res 10:265–275. Schlag J, Schlag-Rey M. 1984. Visuomotor functions of central thalamus in monkey: II. Unit activity related to visual events, targeting, and fixation. J Neurophysiol 51:1175–1195.
T. SHIROYAMA ET AL. Shiroyama T, Kayahara T, Yasui Y, Nomura J, Nakano K. 1995. The vestibular nuclei of the rat project to the lateral part of the thalamic parafascicular nucleus (centromedian nucleus in primates). Brain Res 704:130–134. Spiegel E, Szekely E, Gildenberg P. 1965. Vestibular responses in midbrain, thalamus, and basal ganglia. Arch Neurol 12:258–269. Swanson LW. 1992. Brain maps: structure of the rat brain. Amsterdam: Elsevier. Tarlov E. 1969. The rostral projections of the primate vestibular nuclei: an experimental study in macaque, baboon and chimpanzee. J Comp Neurol 135:27–56. Thompson SM, Robertson RT. 1987. Organization of subcortical pathways for sensory projections to the limbic cortex: II. Afferent projections to the thalamic lateral dorsal nucleus in the rat. J Comp Neurol 265:189– 202. Tracy DJ, Asanuma C, Jones EG, Porter R. 1980. Thalamic relay to motor cortex: afferent pathways from brain stem, cerebellum, and spinal cord in monkeys. J Neurophysiol 44:532–554. Van Groen T, Wyss JM. 1992. Projections from the laterodorsal nucleus of the thalamus to the limbic and visual cortices in the rat. J Comp Neurol 324:427–448. Vermersch A-I, Mu¨ri RM, Rivaud S, Vidailhet M, Gaymard B, Agid Y, Pierrot-Deseilligny C. 1996. Saccade disturbances after bilateral lentiform nucleus legions in humans. J Neurol Neurosurg Psychiatry 60:179–184. Wepsic JG. 1966. Multimodal sensory activation of cells in the magnocellular medial geniculate nucleus. Exp Neurol 15:299–318.