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Department of Physiology and Pharmacology, Göteborg University, 405 30 Göteborg, Sweden
Submitted 15 September 2003; accepted in final form 5 November 2003
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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-motoneurons and (2) to determine both the supraspinal and spinal relays of these actions. Axons of fastigial neurons were stimulated at the level of their decussation in the cerebellum, within the hook bundle of Russell, in deeply anesthetized cats with only the right side of the spinal cord intact. The resulting excitatory postsynaptic potentials and inhibitory postsynaptic potentials were analyzed in motoneurons on the left side of the lumbar enlargement. Postsynaptic potentials evoked by the first effective stimulus were induced at latencies <2 ms from descending volleys and <1 ms from interneuronally relayed volleys, indicating a trisynaptic coupling between the fastigial neurons and -motoneurons, via commissural interneurons on the right side. Cerebellar stimulation facilitated the synaptic actions of both vestibulospinal and reticulospinal tract fibers. However, the study leads to the conclusion that trisynaptic fastigial actions are mediated via vestibulospinal rather than reticulospinal tract fibers [stimulated within the lateral vestibular nucleus (LVN) and the medial longitudinal fascicle (MLF), respectively]. This is indicated firstly by collision between descending volleys induced by cerebellar stimulation and volleys evoked by LVN stimuli but not by MLF stimuli. Second, similar cerebellar actions were evoked before and after a transection of MLF. Mutual facilitation between the fastigial and reticulospinal, as well as between the fastigial and vestibulospinal actions, could be due to the previously reported integration of descending vestibulospinal and reticulospinal commands by spinal commissural interneurons. |
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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; Wilson et al. 1978). However, they may also influence postural and locomotor reactions of the whole body (Mori et al. 1998, 1999). Early observations on effects of stimulation of the fastigial nucleus on hindlimb motoneurons suggested that these effects were evoked via polysynaptic pathways, in view of the long (10-20 ms) latency of the earliest excitatory postsynaptic potentials (EPSPs) (Sasaki and Tanaka 1963) and of long duration of facilitation of monosynaptic reflexes (Asratian and Grigorian 1979). However, subsequent studies indicated that the earliest fastigial actions could be evoked by much more direct pathways. For instance, fastigial actions could be evoked di- or trisynaptically if they were mediated by reticulospinal, vestibulospinal, or long propriospinal neurons that are monosynaptically activated by fastigial neurons (Alstermark et al. 1987a,b; Homma et al. 1995; Mori et al. 1998) and have mono- or disynaptic actions on hindlimb motoneurons. Coupling between long propriospinal neurons and motoneurons has not yet been investigated but mono- and disynaptic coupling between reticulospinal or vestibulospinal neurons and ipsilateral -motoneurons has been long known (Floeter et al. 1993; Gossard et al. 1996; Grillner and Lund 1968; Jankowska et al. 2003; Lund and Pompeiano 1968; Shapovalov 1969; Wilson and Yoshida 1969). Disynaptic coupling from both reticulospinal and vestibulospinal neurons has been also found for contralateral -motoneurons (Aoyama et al. 1971; Bannatyne et al. 2003a,b; Gossard et al. 1996; Grillner 1970, 1971; Hongo et al. 1971; Jankowska et al. 2003; Krutki et al. 2003; Maeda et al. 1975; Shapovalov 1969).
The main aim of this study was therefore to verify the existence of trisynaptic coupling between fastigial neurons and contralateral -motoneurons via commissural interneurons, as diagrammatically indicated in Fig. 1A. The second aim was to investigate whether any EPSPs or inhibitory postsynaptic potentials (IPSPs) evoked in this way were mediated via reticulospinal or vestibulospinal tract neurons or by both. This was done by establishing whether spatial or temporal facilitation occurs at a premotoneuronal level between effects of stimuli applied to axons of fastigial neurons (within the hook bundle of Russell) (Rasmussen 1933) and to axons of reticulospinal neurons within the medial longitudinal fascicle (MLF) in the medulla or within the lateral vestibular nucleus (LVN). Since MLF contains reticulospinal tract fibers originating either in pontine or in bulbar reticular nuclei (Basbaum et al. 1978; Matsuyama et al. 1988 1993; Mitani et al. 1988a), no attempt was made to differentiate between effects of reticulospinal fibers of different origin. Results of pilot experiments (Nakajima et al. 2000) and preliminary results of this study (Matsuyama and Jankowska 2003) have been published in an abstract.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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The experiments were performed on seven deeply anesthetized cats (weighing 2.6-3 kg). Anesthesia was induced by pentobarbital sodium (40 mg/kg ip) and maintained first with pentobarbital (in doses of 1-2 mg/kg iv up to a total of 45 mg/kg), and thereafter with -chloralose (Alpha Chloralose, Rhoône Poulenc Santé, France; in doses of 5 mg/kg up to a total of 55 mg/kg). Full anesthesia was verified from the lack of withdrawal and corneal reflexes before neuromuscular transmission was blocked and by monitoring of the diameters of the pupils, heart rate, and blood pressure throughout the experiment, to ensure that they did not respond to noxious stimulation. Mean blood pressure was kept between 90 and 130 mmHg and the CO2 level in the expired air was kept near 4%, by adjusting the volume of artificial respiration and a rate of a continuous infusion of a bicarbonate buffer solution with 5% glucose (1-2 ml/kg/h). The animal's core temperature was maintained at 37-38°C using heating lamps. Bilateral pneumothorax was made to reduce respiratory movements and to improve the recording stability. All the experimental procedures were approved by Göteborg ethics committee and followed National Institutes of Health and EU guidelines of animal care. At the end of the experiment an overdose of anesthetic was given and the animals were perfused with 4% solution of paraformaldehyde. A preliminary dissection included canulation of the trachea, a carotid artery (for continuous monitoring of blood pressure), and left and right cephalic veins (for intravenous injection of anesthetics and other fluids). A number of peripheral left and right hindlimb nerves were dissected, transected, and mounted on stimulating electrodes: either subcutaneous cuff electrodes [for the quadriceps (Q) and sartorius (Sart) nerves] or pairs of silver hook electrodes in a paraffin oil pool [for the posterior biceps and semitendinosus (PBST), anterior biceps and semimembranosus (ABSM), and gastrocnemius and soleus (GS) nerves]. Laminectomies were performed at the level of lower thoracic (Th11-Th13) and upper lumbar to sacral (L2-S1) segments. The cerebellum was exposed to allow insertion of two or three stimulating electrodes. To restrict the population of descending tract neurons mediating fastigial actions to those with axons on one side of the spinal cord, other tract fibers were eliminated by spinal hemisection at Th 12 (as indicated in Fig. 1A). The dorsal columns were removed over a distance of a few millimeters, the central canal was visualized, and the tissue lateral to it was separated intrapially with watchmakers' forceps over a distance of 2-3 mm until the surface of the ventral funiculus on the opposite side was reached.
Placement of the brain stem and cerebellar electrodes and histological verifications.
Electrodes were inserted through cerebellum at an angle of 35° (tip directed rostrally). The initial target positions were the hook band of Russel at Horsley-Clarke co-ordinates posterior (P) 7, lateral (L) 0, horizontal (H) 0; the MLF at coordinates P 9 to 10, L 0.7, H -5; and the LVN at coordinates P 7.5 to 8, L 4-4.5, H -2 to -3, but the final position of all of these electrodes was adjusted on the basis of records of descending volleys from the surface of the lateral funiculus at a Th11-Th13 level, as illustrated in the results. The electrodes were left at sites from which distinct descending volleys were evoked at thresholds of 10-20 µA and were near maximal at 100-150 µA. These stimulation sites were marked at the end of the experiments with electrolytic lesions (0.3 mA for 15 s) and were verified on 100-µm-thick frontal sections of the brain stem. The sections were cut in the plane of insertion of the electrodes using a freezing microtome and were counterstained with cresyl violet. The distribution of the stimulation sites is indicated in Fig. 2A and B (in the cerebellum), E (in LVN), and F (in MLF). In three animals the MLF was transected by inserting a narrow spatula (width 3 mm) or a piece of plastic film (0.1 mm thick, 3 mm wide, 10 mm long) into the midline of the medulla a few milimeters caudal to the MLF stimulation site. The plastic film was left in place during the experiment and was removed only after the brain had been fixed by perfusion.
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Axons of the reticulospinal, vestibulospinal, and fastigial neurons were stimulated using a 0.5-mm electrolytically etched tungsten wire electrode, insulated except for its tip as a cathode and a wire inserted into a neck muscle as an anode. Constant current single, double, or triple stimuli 3.3 or 5.0 ms apart (0.2 ms, 50-150 µA) were used. Peripheral nerves were stimulated with constant voltage stimuli [0.1 ms, intensity expressed in multiples of threshold (T) for the most sensitive fibers in a given nerve].
Intracellular records from motoneurons were made using glass micropipettes (1.5-2.0 µm tip diam) filled with a 2 M potassium citrate solution. The reported results are based on records from 65 motoneurons located in the 4th, 5th, or 7th lumbar segments. Simultaneous records of incoming afferent and descending volleys were taken from the surface of the spinal cord with a silver ball electrode in contact with the dorsal columns close to the dorsal roots entry zone or in contact with the lateral funiculus on the side of location of the motoneurons, usually within 5-10 mm of the microelectrode recording site. DC recording or low-pass filters of 1 Hz were used when recording from motoneurons and both the original records and averages of 10-50 single sweep records were stored (using software designed by E. Eide, N. Pihlgren, and T. Holmström, Dept. of Physiology, Göteburg University). The measurements of amplitudes, areas, and latencies of postsynaptic potentials (PSPs) and descending volleys were made from the averaged records. Student's t-test was used for the statistical analysis. Records were reproduced using CorelDraw 8.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Stimuli applied at several locations in the midline region of the cerebellum evoked distinct descending volleys at a thoracic level, but those from locations corresponding to the region where a thick bundle of fibers running transversely crossed the midline (the hook bundle of Russell) were largest. Figure 2, A and C, illustrates this with data from an experiment in which the most distinct volleys were evoked from depths labeled +0.5 to -1 (corresponding to Horsley-Clarke's coordinates H +1.2 to 0), the site indicated by an arrow in Fig. 2A having been selected for testing effects of the cerebellar stimulation. Stimulation sites selected in other experiments are indicated in Fig. 2B. When the electrode was inserted at different rostrocaudal levels, the largest volleys were evoked from locations corresponding to Horsley-Clarke coordinates P 6.5 to 7 (Fig. 2D) and again were restricted to the region of the hook bundle of Russell.
Latencies of descending volleys evoked by cerebellar stimuli (2.66 ± 0.08 ms; mean ± SE; n = 7) were about 0.8 ms longer than latencies of descending volleys evoked by MLF stimuli (1.86 ± 0.04 ms; n = 7) and about 0.7 or 0.2 ms longer than latencies of descending volleys evoked by LVN, as illustrated in Fig. 2, C and G. Because fastigial neurons have been found to activate reticulospinal as well as vestibulospinal neurons (Alstermark et al. 1987a,b; Homma et al. 1995; Mori et al. 1998), effects of cerebellar stimuli could be relayed by either or both of these descending tract fibers. The following attempts were therefore made to estimate to what extent the reticulospinal and vestibulospinal tract neurons might contribute to the descending volleys evoked from the cerebellum.
First a comparison was made of the spinal rostrocaudal distribution of the descending volleys of the cerebellar, LVN, and MLF origin. Figure 3,A-C, shows that the cerebellar and LVN volleys were distinct rostral to the L4 segment but became difficult to detect at more caudal levels (as previously found for LVN volleys by (Krutki et al. 2003), whereas early components of the MLF volleys remained as distinct at lower as at upper lumbar levels and their second component (marked by an asterisk) increased, in particular at the L5-L7 levels (Jankowska et al. 2003). Similar differences were found in all three experiments in which they were analyzed. The parallel distribution of the cerebellar and LVN volleys and more caudal extent of the late component of the MLF volleys are thus more in keeping with the cerebellar volleys reflecting activity in the vestibulospinal than in the reticulospinal tract fibers.
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Third, the following tests were made to examine the possibility that effects of cerebellar stimuli were relayed by the same fibers that were stimulated within the LVN but not by fibers stimulated in MLF. If the cerebellar stimuli did activate the same fibers, then these fibers could not be activated twice when intervals between the stimuli were very short. The minimal effective intervals should be longer than the refractory period following activation of vestibulospinal or reticulospinal tract neurons. In the case of LVN stimulation, they should in addition be longer than twice the conduction time between LVN and the cerebellum during which nerve impulses that are orthodromically and antidromically conducted along axons of fastigial neurons would collide. Stimuli to the LVN or MLF were therefore applied within 2 ms before or after the cerebellar stimuli. The stimuli were near maximal (100-200 µA) and they were expected to activate fibers within a radius of 1-2 mm (Gustafsson and Jankowska 1976) but without spread of current to the other stimulation sites. Records in Figs. 2, C, G, and J and 3D argue against such a spread of current since minimal latencies of the earliest components of the cerebellar, MLF, and directly induced LVN volleys always differed, when stronger as well as when weaker stimuli were used.
In Fig. 4 the compound volleys evoked by joint actions of pairs of the cerebellar, LVN, and MLF stimuli (labeled "both") are compared with the sums of the volleys evoked by each of them separately. When the same fibers were stimulated twice at a very short interval, as in Fig. 4F, the differences (bottom traces) were as large as the volleys evoked by either the first or the second stimulus, indicating that the fibers activated by the first stimulus were refractory to the second stimulus. The large difference in Fig. 4A indicates thus that the descending volleys evoked by the cerebellar stimuli may have been relayed by LVN neurons that were made refractory to the LVN stimuli. Descending volleys of cerebellar origin may accordingly reflect activity in axons of vestibulospinal neurons that were synaptically activated by fastigial neurons. In contrast, there was hardly any difference when the LVN stimuli were delivered at a longer interval (Fig. 4B), indicating that at this interval the LVN neurons could be activated by both stimuli. The same effects were seen in experiments in which LVN volleys were induced indirectly or were induced both directly and indirectly. In similar tests with other combinations of stimuli, the volleys summed linearly: between the cerebellar and MLF stimuli (Fig. 4, C and D; in 4 experiments) or between the LVN and MLF stimuli (Fig. 4E; in 2 experiments). This indicates that the descending volleys evoked by these stimuli reflected activity in distinct fibers activated by them.
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Effects of cerebellar stimuli on motoneurons
Effects of cerebellar stimuli were analyzed in a sample of 65 motoneurons recorded in the L4th, 5th, and 7th segments. The motoneurons included 12 PBST, 35 GS, 11 Q, and 7 Sart motoneurons, all with action potentials 50-75 mV and with stable membrane potential during the whole period of recording. When trains of three stimuli near maximal for the cerebellar descending volleys were applied, EPSPs or IPSPS following these stimuli were found in only a proportion of the motoneurons. EPSPs were evoked in 26 (PBST, GS, and Q) and IPSPs in 9 (Sart and GS) motoneurons, totally in 54% of 65 motoneurons tested. EPSPs or IPSPs from LVN were evoked in 6 and 4, totally 30% of 34 motoneurons tested. In contrast, EPSPs or IPSPs from MLF were evoked in all 40 motoneurons tested. As illustrated in Fig. 5, both the EPSPs and IPSPs of cerebellar origin were in addition much smaller than those evoked from MLF in the same motoneurons. The minimal PSPs that repeatedly followed cerebellar stimuli at the same latency were of about 0.1 mV in averaged records and 0.1-0.2 mV in single sweep records. Their maximal amplitudes were within the same ranges (0.1-0.5 mV) as those of EPSPs and IPSPs of LVN origin (0.1-0.3 mV). Greater numbers of cerebellar and LVN stimuli were always needed to evoke EPSPs or IPSPs compared with MLF stimuli. The separation between dotted lines in Fig. 5A shows in addition that the latency of EPSPs evoked by cerebellar stimuli (5.31 ± 0.04 ms; mean ± SE) was about 1 ms longer than the latency of EPSPs from MLF (4.18 ± 0.08 ms; P < 0.001) and similar to the latency of EPSPs from LVN (5.36 ± 0.07 ms; P > 0.5) when measured from stimulus artifacts. Differences in latencies of the IPSPs were also of about 1 ms (Fig. 5, D and E). These data are thus compatible with two relay neurons between the fastigial neurons and contralateral motoneurons compared with only one relay neuron between MLF fibers and these motoneurons (Jankowska et al. 2003; Krutki et al. 2003).
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Interactions between the synaptic actions of cerebellar and LVN stimuli on motoneurons
Figure 6B illustrates effects of combining cerebellar and LVN stimuli, both of which failed to evoke any EPSPs when applied alone (Fig. 6, A and C) on a motoneuron. When the stimuli were separated by 1 ms or more, they evoked a distinct EPSP but the mutual facilitation between their actions disappeared when one stimulus fell into the collision/refractory period following the other one. The time course of this facilitation is plotted in Fig. 6G, a similar plot for another motoneuron shown in Fig. 6H. A similar time course of facilitation was found in all 19 motoneurons in which it was investigated.
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Similar facilitation, and with a similar time course, occurred in six motoneurons when the cerebellar and LVN stimuli evoked IPSPs (Fig. 6, D-F and I). Facilitation of both EPSPs and IPSPs was maximal when cerebellar stimuli were applied in the center of the area of the hook bundle of Russell and when LVN stimuli were applied within the limits of the LVN (Fig. 7).
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Interactions between cerebellar and MLF synaptic actions on motoneurons
As shown above, the operation of reticulospinal pathways is not a prerequisite for fastigial actions on contralateral motoneurons and it appears unlikely that trisynaptic actions of fastigial neurons would be in a significant way relayed by reticulospinal neurons with axons in MLF. Reticulospinal tract neurons that are activated by fastigial neurons via other neurons might nevertheless increase the probability of activation of commissural interneurons mediating actions of fastigial and LVN neurons. To investigate this possibility we analyzed mutual facilitation between the cerebellar and MLF actions on motoneurons in the same way as facilitation between the cerebellar and LVN actions.
Figure 8 shows that the facilitation following cerebellar and MLF stimulation was as potent as that following cerebellar and LVN stimulation and that it involved both EPSPs and IPSPs; it was found in all 25 and 15 motoneurons tested, respectively. However, an important difference was found in the time course of this facilitation. As shown in Fig. 8, G and H, it was always most potent when the MLF and cerebellar volleys coincided or followed each other within a fraction of a millisecond (intervals indicated by thick lines above the abscissa). This time course was found for facilitation of all 14 EPSPs and all 4 IPSPs analyzed, both when single (Fig. 8, B and C) and double (Fig. 8, E and F) MLF stimuli were used. The second (spinally relayed) components of the descending volleys, indicated by arrowheads in Fig. 8B, were particularly large at these intervals. They thus strongly relate the facilitation with more potent activation of commissural interneurons (for arguments that these components represent a spinally relayed event, see Jankowska et al. 2003). The strongest facilitation of both EPSPs and IPSPs of MLF origin was evoked from the center of the area of the hook bundle of Russell, as in the experiment illustrated in Fig. 7, A and D.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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The effects evoked by cerebellar stimulation can be attributed to the axons of fastigial neurons since these effects were evoked from within the width of the midline cerebellar white matter through which these axons cross and the effects of stimuli of 50-100 µA (with the estimated spread of current of 0.5-1 mm) declined when the stimulating electrode was moved more than about 0.5 mm above or below the hook bundle of Russell. In addition, stimuli delivered more than 1 mm more rostral or caudal to this site evoked much weaker effects. The most effective stimulation sites overlapped with the areas from which retrograde labeling of fastigial neurons (Homma et al. 1995) and anterograde labeling of fastigiofugal fibers projecting to the nucleus reticularis gigantocellularis and magnocellularis and to vestibular nuclei (Homma et al. 1995; Mori et al. 1999) were obtained. These sites likewise overlapped or were within about 0.5 mm of the sites from which both the bilateral postural reactions and locomotor movements of the hindlimbs could be induced by electrical stimulation in decerebrated animals (Asanome et al. 1998; Matsuyama and Mori 1998; Mori et al. 1989, 1998, 1999; Nakajima et al. 2000).
The effects of stimuli applied in MLF and LVN are attributed to axons of reticulospinal and vestibulospinal tract neurons relying on previous control experiments (Jankowska et al. 2003; Krutki et al. 2003). In addition, to minimize the spread of current, we used the weakest effective currents and always verified that effects induced by stimuli applied within MLF or LVN were not reproduced when the stimulating electrodes were moved outside these structures. Transsynaptic activation of other neurons via axon collaterals of either reticulospinal or vestibulospinal neurons, or of neurons providing input to them, could not be excluded. However, the probability of actions evoked by axon collaterals of reticulospinal neurons (e.g., Mitani et al. 1988a,b,c) or of neurons stimulated within LVN was reduced by the demonstration that the main reported effects of reticulospinal neurons disappeared after a lesion of MLF within the more caudal part of the medulla, whereas those from the cerebellum and LVN remained. For discussion of other methodological problems related to stimulation of MLF and LVN see Jankowska et al. (2003) and Krutki et al. (2003).
Reticulospinal versus vestibulospinal relay of fastigial actions
Reticulospinal neurons were expected to be involved in mediating actions of fastigial neurons in view of the previous evidence for a strong coupling between neurons in the fastigial nuclei and at least some neurons in the reticular formation (Mori et al. 1998). However, several of our observations argue against the mediation of the most direct fastigial actions by reticulospinal neurons with axons in the MLF. The most decisive of these observations was that, when the descending volleys following MLF stimuli were abolished by a lesion of the MLF at a more caudal level, LVN and cerebellar stimuli continued to evoke descending volleys (Fig. 3) as well as trisynaptic EPSPs and IPSPs in motoneurons. The lack of collision or of any interactions due to refractoriness of the MLF fibers when the cerebellar and MLF stimuli were applied in quick succession (Figs. 4 and 8) are likewise incompatible with the activation of MLF fibers by stimuli applied in the hook bundle of Russell.
In contrast, the interactions between effects of the cerebellar and LVN stimuli applied during collision and/or refractory periods following one of them (Figs. 4 and 6) were what would be expected for effects mediated via the same fibers. The similar appearance of the descending volleys and cord dorsum potentials evoked by the cerebellar and LVN stimuli recorded in the midlumbar segments is also in keeping with this possibility and, as shown in Fig. 3, clearly differs from the appearance of the volleys evoked from MLF. The question of the relative contribution of vestibulospinal and propriospinal neurons (see Fig. 1) to the descending volleys of cerebellar origin after MLF lesions, and to fastigial actions on contralateral motoneurons, has not been addressed in this study and remains open.
Spinal relay of fastigial actions on hindlimb motoneurons
Previous studies have shown that vestibulospinal and reticulospinal neurons excite or inhibit contralateral motoneurons both via single interposed spinal commissural interneurons, i.e., disynaptically and polysynaptically (Jankowska et al. 2003; Krutki et al. 2003). Since the earliest components of the EPSPs and IPSPs evoked by cerebellar stimuli were induced at latencies that were only about 1 ms longer than of the earliest components of PSPs of MLF origin, they might have been evoked trisynaptically. EPSPs and IPSPs mediated via vestibulospinal tract fibers would be relayed by commissural interneurons located on the same side of the spinal cord in view of ipsilateral terminal branching areas of these fibers in the lumbosacral enlargement (Holstege and Kuypers 1982; Kuze et al. 1999). Reticulospinal neurons that are either directly or indirectly activated by fastigial neurons could act via the same interneurons (Krutki et al. 2003; Skinner and Remmel 1978) but they could also activate interneurons on the opposite site of the spinal cord, via crossed local axon collaterals of reticulospinal tract fibers (Matsuyama et al. 1988, 1997, 1999; Peterson et al. 1975). However, since no evidence for the contribution of reticulospinal neurons with axons in MLF to fastigial actions investigated has been found in this study, our conclusions can be restricted to fastigial actions mediated by commissural interneurons. Commissural interneurons that are monosynaptically excited from MLF and LVN and project to contralateral motor nuclei (Krutki et al. 2003) form synaptic contacts with motoneurons and their terminals contain either glutamate or glycine (Bannatyne et al. 2003b). Subpopulations of these neurons might thus mediate disynaptic excitation or inhibition of reticular and vestibulospinal origin and be interposed in trisynaptic excitatory and inhibitory pathways between fastigial neurons and contralateral motoneurons as indicated in Fig. 1B.
Functional consequences
We wish to stress two main corollaries of the network of neurons mediating actions of fastigial neurons on contralateral motoneurons outlined above. The first is that fastigial neurons may coordinate movements of the two hindlimbs with movements of the forelimbs, trunk, and head via a minimal number of additional spinal relay neurons. The second is that adjustments of postural reactions by fastigial neurons via vestibulo- and reticulospinal descending systems involve integration of descending commands that to a great extent occurs at a spinal level. Our results show that commissural interneurons with direct actions on motoneurons are important in this integration. However, when the spinal cord is intact, and not hemisected as in preparations used in this study, other neurons may be involved. These neurons might, e.g., include interneurons with input from vestibulo- and reticulospinal neurons, located at the same side as the motoneurons or providing polysynaptic input to commissural interneurons. These possibilities have not been included in the diagram of Fig. 1 but might be considered in future studies.
A discussion of consequences of the apparently negligible contribution of reticulospinal neurons with axons in MLF to the most direct actions of fastigial neurons in the lumbar segments and their role in mediating locomotion induced by cerebellar stimuli (Mori et al. 1998, 1999) is outside the scope of the present study. However, our results indicate that it would be interesting to compare the role of different populations of reticular and vestibular neurons and of their target neurons in the effects of such stimuli.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Present address of K. Matsuyama: Department of Physiology, Sapporo Medical University School of Medicine, Sapporo, 060-8556 Japan
GRANTS
The study was supported by National Institute of Neurological Disorders and Stroke Grant NS-40 863.
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FOOTNOTES |
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Address for reprint requests: E. Jankowska, Dept. of Physiology and Pharmacology, Medicinaregatan 11, Box 432 405 30, Göteborg, Sweden (E mail: Elzbieta.Jankowska{at}physiol.gu.se).
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REFERENCES |
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