* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Functional Specialization Within the Cat Red Nucleus
Development of the nervous system wikipedia , lookup
Endocannabinoid system wikipedia , lookup
Environmental enrichment wikipedia , lookup
Neuroanatomy wikipedia , lookup
Embodied language processing wikipedia , lookup
Central pattern generator wikipedia , lookup
Proprioception wikipedia , lookup
Perception of infrasound wikipedia , lookup
Feature detection (nervous system) wikipedia , lookup
Premovement neuronal activity wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Synaptogenesis wikipedia , lookup
Caridoid escape reaction wikipedia , lookup
Channelrhodopsin wikipedia , lookup
Electromyography wikipedia , lookup
Anatomy of the cerebellum wikipedia , lookup
Eyeblink conditioning wikipedia , lookup
Hypothalamus wikipedia , lookup
Synaptic gating wikipedia , lookup
Circumventricular organs wikipedia , lookup
Optogenetics wikipedia , lookup
Evoked potential wikipedia , lookup
Microneurography wikipedia , lookup
Transcranial direct-current stimulation wikipedia , lookup
J Neurophysiol 87: 469 – 477, 2002; 10.1152/jn.00949.2000. Functional Specialization Within the Cat Red Nucleus K. M. HORN, M. PONG, S. R. BATNI, S. M. LEVY, AND A. R. GIBSON Division of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona 85013 Received 29 December 2000; accepted in final form 14 August 2001 The accompanying report (Pong et al. 2002) demonstrates that projections of the parvicellular red nucleus (RNp) are stronger at upper cervical levels than at lower cervical levels. In contrast, projections of magnocellular red nucleus (RNm) are stronger at lower cervical levels than at upper levels. RNm receives a major input from the cerebellar interpositus nucleus, and RNp receives a major input from the cerebellar dentate nucleus. It is likely that RNm and RNp serve different functions in movement control. Cells in the red nucleus (RN) discharge strongly during reaching to grasp an object (Gibson et al. 1985, 1994; van Kan and McCurdy 2001). The differential spinal projections indicate that RNp may be more important for control of muscles in the proximal limb, whereas RNm may be more important for control of muscles of the distal limb. However, most termina- tions of rubrospinal (RST) fibers are to spinal interneurons rather than to motor neurons, and terminations at one spinal level might influence motor neurons at other levels via propriospinal connections (Alstermark et al. 1990; Robinson et al. 1987). The object of the present study was to test the hypothesis that activation of RNp neurons will produce activity in muscles of the proximal limb and activation of RNm neurons will produce activity in muscles of the distal limb. Fetz and Cheney (1980) developed the technique of spiketriggered averaging of electromyography (EMG) to detect functional relations between cellular activity and muscle activation. By synchronizing the EMG records to the activity of a single neuron it is possible, with sufficient averaging, to detect the contribution that the neuron makes to activation of the target muscle. A variation of spike-triggered averaging is stimulus-triggered averaging, which elicits neural activity with electrical stimulation. Stimulus-triggered averaging has some practical advantages over spike-triggered averaging. One advantage is that the experimental demands are less because single units do not need to be isolated for a prolonged averaging period. A second advantage is that stimulation has a relatively strong effect on muscle activation because more than one neuron is activated by the stimulus pulse. These advantages allow more data to be collected from each subject; this is an important consideration when dealing with behaving animals with EMG electrodes implanted into several muscles. Direct comparisons between spike- and stimulus-triggered averaging in motor cortex (Cheney and Fetz 1985) and red nucleus (Cheney et al. 1991) indicate that patterns of EMG facilitation and suppression are in good agreement between the two methods. However, stimulus-triggered averaging has a drawback in that activation of fibers passing near the stimulation site may confound the results. This is a major concern with stimulation within the RN because cerebellar efferents course through the nucleus to terminate in more rostral regions of RN as well as thalamus. Additionally, efferents from lateral regions of RN pass through medial regions of the nucleus as they decussate to form the rubrospinal tract (RST). Data from the cases reported in the preceding paper (Pong et al. 2002) show that, for a short distance after decussation, the fibers from RNp and RNm are segregated in the RST. The RNm fibers travel dorsally to fibers from RNp until they reach caudal pontine levels where they intermingle. In this paper, we compare stimulus-triggered averages (StTAs) of forelimb muscles with stimulation sites in Address for reprint requests: K. M. Horn, Div. of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013 (E-mail: [email protected]). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. INTRODUCTION www.jn.org 0022-3077/02 $5.00 Copyright © 2002 The American Physiological Society 469 Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 Horn, K. M., M. Pong, S. R. Batni, S. M. Levy, and A. R. Gibson. Functional specialization within the cat red nucleus. J Neurophysiol 87: 469 – 477, 2002; 10.1152/jn.00949.2000. Magnocellular (RNm) and parvicellular (RNp) divisions of the cat red nucleus (RN) project to the cervical spinal cord. RNp projects more heavily to upper cervical levels and RNm projects more heavily to lower levels. The cells in RN are active during reaching and grasping, and the differences in termination suggest that the divisions influence different musculature during this behavior. However, the spinal termination may not reflect function because most rubrospinal terminations are to interneuronal regions, which can influence motor neurons at other spinal levels. To test for functional differences between RNm and RNp, we selectively stimulated RNm and RNp as well as the efferent fibers from each region. Electromyographic activity was recorded from seven muscles of the cat forelimb during reaching. The activity from each muscle was averaged over several thousand stimuli to detect influences of stimulation on muscle activity. Stimulation within the RN produced a characteristic pattern of poststimulus effects. The digit dorsiflexor, extensor digitorum communis (edc), was most likely to show facilitation, and several other muscles showed suppression. The pattern of activation did not differ between RNm and RNp. In contrast, stimulation of RNp fibers favored facilitation of shoulder muscles (spinodeltoideus and supraspinatus), and stimulation of RNm fibers favored facilitation of digit and wrist muscles (edc, palmaris longus, and extensor carpi ulnaris). Fiber stimulation produced few instances of poststimulus suppression. The results from fiber stimulation indicate that the physiological actions of RNm and RNp match their levels of spinal termination. The complex pattern of facilitation and suppression seen with RN stimulation may reflect synaptic actions within the nucleus. 470 HORN, PONG, BATNI, LEVY, AND GIBSON METHODS Behavioral paradigm Five cats were trained to reach, grasp, and retrieve a handle on presentation of a tone. The cats received a small quantity of pureed chicken and cod liver oil extruded from the end of the handle. Cats typically performed 200 –500 trials during daily training sessions of 1–2 h. The cats were provided supplemental food in their home cages to maintain their body weights between 80 and 100% of free-feeding weight. Implant surgery Surgery was performed in an American Association of Laboratory Animal Care-approved surgical suite using aseptic techniques. All procedures were approved by the St. Joseph’s Hospital Institutional Animal Care and Use Committee and were in accordance with National Institutes of Health guidelines. Each cat was initially anesthetized with an intramuscular injection of ketamine hydrochloride (10 –15 mg/kg), and anesthesia was maintained with intravenous administration of pentobarbital sodium. A recording chamber and a head restraint device were fastened to the skull with stainless steel screws and dental acrylic. For three cats, the chamber was positioned to provide access to the RN (A4.0, Berman 1968). In one cat, the chamber was positioned (P2.0) to provide access to the RST at mesencephalic levels, and, in another, the chamber was positioned to provide access to the RST at medullary levels (P10.0). For each cat, seven pairs of insulated multi-stranded stainless steel wire were implanted into forelimb muscles. Each electrode had a tip exposure of 4 – 6 mm, and the tips of each pair were separated by 5–10 mm. Placement was confirmed by electrical stimulation through the electrodes. Table 1 lists the implanted muscles and their physiological actions. RST tracing TABLE 1. Implanted forelimb muscles Muscle Joint Action Physiological Role Extensor digitorum communis (edc) Palmaris longus (pl) Extensor carpi ulnaris (ecu) Triceps (long head) (tri) Brachialis (br) Spinodeltoidius (sd) Supraspinatus (ss) Digit extensor Digit flexor Wrist extensor Elbow extensor Elbow flexor Shoulder flexor Shoulder adductor Flexor Extensor Flexor Extensor Flexor Flexor Flexor The actions that the muscles with implanted electromyographic electrodes exert about the forelimb joints and their physiologic anti-gravity roles. Neural and EMG recordings Neural activity within the RNm or RST was recorded with tungsten microelectrodes. Cells in RNm and RNp discharged during movements of the contralateral limbs. Spike amplitudes from cells in RNp tended to be smaller than amplitudes of cells in RNm, and fiber recordings in RST were characterized by waveforms with initial positive deflections (van Kan et al. 1993). EMG activity was recorded with a band-pass of 10 –10,000 Hz, full-wave rectified, integrated with a 1-ms time constant and sampled at 4 kHz. Prior to each recording session, the amplifier gain for each muscle was set to provide peak amplitudes of 5 V during the behavioral task. This procedure was meant to help compensate for changes in electrodes over time as well as for variations between muscles and cats. Examples of the rectified and integrated EMG signals from four muscles during a reach trial are illustrated in Fig. 1A. StTA and data analysis StTA of rectified EMG activity were calculated for the different RN and RST sites. The techniques used in the present study are similar to those of Cheney et al. (1991). Stimuli were applied at 500- or 1,000-m increments along each electrode track. During stimulation, monophasic negative pulses (0.2-ms duration, 10 Hz, 5–30 A) were delivered through the tungsten recording electrode while the cat performed the reaching task. The patterns of muscular activation near threshold (5–10 A) resulted in similar StTA patterns as generated with the suprathreshold current of 20 A. Data presented in this report were collected using stimuli of 20 A with EMG averaged for 2,000 pulses. StTAs were calculated by computing an average baseline activity and standard deviation (SD) from 10-ms periods preceding the stimulus pulses. Data were standardized relative to the SD of the baseline activity. Figure 1B illustrates examples of significant StTAs for the four muscles shown in A. Several criteria were required for a StTA to be considered significant. First, the amplitude of the waveform needed to exceed ⫾3 SDs of baseline activity. Second, the duration of the significant elevation needed to exceed 2 ms. Third, only StTAs with waveforms beginning between 3 and 15 ms following the stimulus pulse were considered as occurring within a physiologically relevant time frame. Verification of stimulation sites The RST tracing presented in this paper is based on case BRN1 of the previous paper (Pong et al. 2002), and the anatomical methods are fully described in that paper. For case BRN1, injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were placed in RNm on the right side and in RNp on the left side (Fig. 3, see also Fig. 2 of Pong et al. 2002). By plotting the location of anterogradely labeled fibers, the trajectories of the descending fibers from these two regions could be compared across sides of the same frontal sections. J Neurophysiol • VOL Marking lesions (⫺10 A for 10 s) were placed at the end of the experiment. Prior to perfusion, cats received an intramuscular injection of ketamine (20 mg/kg) followed by a lethal dose of sodium pentobarbital (approximately 25 mg/kg) delivered in a single rapid iv bolus. Cats were perfused with 10% formalin. The brains were frozen and sectioned at 50 m. Every section through areas of interest was collected and stained with either cresyl violet or neutral red/luxol blue. 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 RN, RST at caudal mesencephalic levels (segregated fibers), and RST at medullary levels (mixed fibers). Stimulation within RN produced both facilitation and suppression of limb muscle activity and showed a strong bias in favor of facilitating a digit muscle, extensor digitorum communis (edc). However, the overall pattern of muscle activation was similar for stimulation sites in RNm and RNp. At the mesencephalic stimulation site, stimulation of dorsal regions of the RST (RNm fibers) produced strong facilitation of edc but weak facilitation of the shoulder muscles spinodeltoideus (SD) and supraspinatus (ss). Stimulation in the ventral regions of the RST (RNp fibers) produced strong facilitation of the shoulder muscles but weak facilitation of edc. Stimulation of the RST at medullary levels produced facilitation in all limb muscles with few instances of suppression. The results indicate that anatomical differences in spinal terminations between RNp and RNm are reflected by physiological action and suggest that the complex effects seen with RN stimulation may be due to activation of local neural elements. FUNCTIONAL SPECIALIZATION WITHIN THE RED NUCLEUS 471 FIG. 1. Records generated during a reaching trial. A: leg position was monitored with a lever attached at the wrist. Examples of the rectified and integrated (1 ms) electromyogram (EMG) for 4 fourlimb muscles [extensor digitorum communis (edc), palmaris longus (pl), brachialis (br), and supraspinatus (ss)] are illustrated below the position trace. B: the stimulus-triggered averages (StTAs) from the muscles after averaging of 2,000 stimulus pulses. Red nucleus (RN) stimulation produced significant StTAs for all of the illustrated muscles, although pl responded with poststimulus suppression rather than facilitation. The long horizontal dashed lines represent ⫾3 SDs of pretrigger EMG activity. RESULTS Stimulation in RN We first attempted to determine functional relations of RNm and RNp by stimulating at 51 sites within the RN of three cats. Sites located in the caudal 2 mm of the RN (n ⫽ 35) are referred to as RNm, and sites in the rostral 2 mm of the nucleus (n ⫽ 16) are referred to as RNp. Figure 2 illustrates averages from a proximal (ss) and a distal (edc) forelimb muscle for one stimulating track that passed through RNm. For the track illustrated by Fig. 2, two sites (black circles) within RNm produced significant facilitation. Cells at the dorsal site were active during movements of the contralateral forelimb, and cells at the ventral site were active during movement of the contralateral hind limb. Presumably, the current spread of the 20-A pulses either included forelimb regions of RN or activated passing fibers related to forelimb musculature. The StTAs from the illustrated track (Fig. 2) mirror the results obtained from all of the RN stimulation tracks. No significant StTAs were produced by stimulation outside of the borders of the RN (27 sites dorsal to RN and 28 ventral), and the pattern of poststimulus facilitation and suppression was consistent between cats. Figure 6A plots the percentage of significant StTAs for three cats with stimulation sites in RNm. For each cat, the most frequently facilitated muscle was edc (91% of sites), while several other muscles, such as palmaris longus (pl), displayed a high incidence of poststimulus suppression. For both RNm and RNp, the distribution of poststimulus effects between muscles differed significantly from chance (RNm, 2 ⫽ 48.2, 6 df, P ⬍ 0.01; RNp, 2 ⫽ 22.8, 6 df, P ⬍ 0.01). Our hypothesis predicted that proximal limb muscles would more likely be activated by RNp stimulation and distal muscles J Neurophysiol • VOL by RNm stimulation. Although the shoulder muscles, sd and ss, were more likely to be facilitated by RNp stimulation (49 vs. 21%), the overall pattern of muscle activation between RNm and RNp was not significantly different (2 ⫽ 2.9, 6 df, P ⬎ 0.50). Therefore stimulation within RN did not support a functional difference between RNm and RNp. Anatomical separation of RNm and RNp fibers in the RST Stimulation within RN is likely to be confounded by activation of passing fibers. The double injection case (BRN1) of the previous paper (Pong et al. 2002) indicated that stimulation of the RST at the appropriate level might avoid this problem. Figure 3, A and B, illustrates injections (0.008 l) of WGA-HRP (1%) made in RNm (A) and RNp (B) on opposite sides of the brain. Figure 3, C and D, illustrates the locations of RST fibers as they descend to the spinal cord. Position of the labeled fibers was plotted onto images of the sections with the use of a computer-aided plotting system (Image Tracer™). Because the fibers exiting from the RN cross immediately to the opposite side, labeled fibers from the RNp injection (vertical striping) are on the right and those from RNm (horizontal striping) are on the left. The section shown in Fig. 3C is at the level of the caudal mesencephalon and rostral pontine nuclei (A1.6). At this level, fibers from RNm (left) travel immediately below fibers of the superior cerebellar peduncle (BC). Fibers from RNp (right) lie ventral to those from RNm and are bounded on their ventral border by the medial lemniscus (ML). Therefore a stimulating track through the RST at this level would pass first through RNm efferent fibers and then through RNp efferent fibers. Figure 3D illustrates the location of labeled RST fibers at the level of the rostral inferior olive (P12.7). At this level, fibers from RNm and RNp are intermingled and occupy corresponding locations on either side of the brain. 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 Locations of unmarked sites were reconstructed relative to lesion locations. 472 HORN, PONG, BATNI, LEVY, AND GIBSON FIG. 2. Reconstruction of a stimulating track through the caudal RN. Stimulation sites producing significant StTAs are indicated by black circles, and sites without significant StTAs are indicated by white circles. Right: StTAs from a proximal (ss) and distal (edc) forelimb muscle. Only sites within the RN produced significant StTA’s (heavier traces), and both muscles were activated at each site. A fourth cat received RST stimulation in the caudal mesencephalon. The RST was localized by re cording fiber discharge during movement of the ipsilateral limb, and its ventral border was identified by the sensory responses of the underlying ML. Figure 4 illustrates StTAs produced on one track through the mesencephalic RST. An outline of the corresponding frontal MESENCEPHALIC LEVEL. section from BRN1 is included to demonstrate the relative location of fibers from RNm and RNp (labeled fibers from the RNm injection have been transposed to the right side). The plane of section was not identical between the cases so sections were matched by comparing ventral structures. StTAs were collected at 0.5-mm steps in depth along the track. Stimulation sites above the BC or below the ML did not elicit significant StTAs (Fig. 4, white circles). During stimu- FIG. 3. Trajectory of rubrospinal tract (RST) fibers from magno- and parvicellular divisions of the RN (RNm and RNp). A: wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injection site in the caudal pole of the right RNm. B: injection site rostral and lateral in left RNp. C: labeled fibers in the caudal mesencephalon. Due to decussation of the RST fibers, fibers labeled by the RNm injection (horizontal hatching) are on the left side and fibers labeled by the RNp injection (vertical hatching) are on the right. At this level, RNm fibers occupy a location dorsal to the location of RNp fibers. D: location of labeled fibers at the medulla. At medullary levels, fibers from RNm and RNp occupy equivalent locations on either side of the brain stem. J Neurophysiol • VOL 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 Stimulation of RST FUNCTIONAL SPECIALIZATION WITHIN THE RED NUCLEUS 473 lation, significant StTAs ceased abruptly as the electrode entered the ML. However, the anatomical reconstruction of this track placed the two most ventral stimulation points within ML fibers. It is likely that the anatomical reconstruction has some inaccuracy because marking lesions were made during electrode withdrawal. Stimulation sites within the RST produced significant poststimulus facilitation (black circles, Fig. 4). Dorsal stimulation sites facilitated edc but not ss, whereas ventral stimulation sites facilitated ss but not edc. Similar muscle activation patterns were seen on the other stimulation tracks. The histograms in Fig. 6, C and D, illustrate the probability of significant StTAs for the various muscles at stimulation sites within either the dorsal (C) or ventral (D) halves of the RST. The probability of obtaining significant StTAs for edc, pl, and extensor carpi ulnaris (ecu) is higher at dorsal sites, whereas the probability for obtaining significant StTAs for triceps (long head; tr), sd, and ss is higher at ventral sites. Brachialis (br) was activated with approximately equal frequency from dorsal and ventral J Neurophysiol • VOL sites. Poststimulus facilitation was much more commonly produced by mesencephalic stimulation than was poststimulus suppression (88% of the stimulation sites produced facilitation). The largest differences in activation were seen for edc, sd, and ss. At dorsal stimulation sites edc was activated 77% of the time but only 15% of the time at ventral sites. In contrast, sd and ss were activated 7 and 3% at dorsal sites but 35 and 65% at ventral sites. The patterns of activation between dorsal and ventral stimulation sites were significantly different (2 ⫽ 41.2, 6 df, P ⬍ 0.01). At the level of the caudal pons, the fibers of the RST form a relatively compact bundle that travels along the ventrolateral edge of the brain stem. At this level, fibers from RNm and RNp intermingle and disperse evenly throughout the RST. Therefore stimulation should provide an overall picture of relations between RN output and forelimb muscles regardless of the site within the RST. Figure 5 illustrates results from one track passing through MEDULLARY LEVEL. 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 FIG. 4. Reconstruction of a stimulating track in caudal mesencephalon. Sites at the depth of and immediately ventral to the superior cerebellar peduncle (BC)-activated edc but not ss, whereas more ventral sites activated ss but not edc. Sites below the medial lemniscus (ML) did not produce significant StTAs. Significant StTAs are shown as heavy traces. The lower schematic illustrates the relative positions of fibers from RNm (RST-m) and RNp (RST-p). The sections were chosen to match AP level at the depth of the effective stimulation sites. Differences in plane of section and histological processing produced a mismatch at other depths. 474 HORN, PONG, BATNI, LEVY, AND GIBSON the RST at medullary levels. Stimulation dorsal and ventral to the RST (white circles) failed to produce significant StTAs, but stimulation within the RST (black circles) did. StTAs for ss and edc are illustrated in Fig. 5, right. Significant StTAs commence at the same depth for both muscles and the largest StTAs are elicited at the same stimulation site. To test for a potential topography within the RST at medullary levels, we grouped the stimulation sites into dorsal and ventral halves based on recording depth (as was done for the RST at mesencephalic levels). Figure 6, E and F, illustrate the results. The patterns of activation for the dorsal and ventral sites were not significantly different (2 ⫽ 0.93, 6 df, P ⬎ 0.50). As with stimulation of the mesencephalic RST, few instances of poststimulus suppression were observed (95% of the sites produced facilitation). DISCUSSION The primary objective of this study was to determine if spinal terminations of RNm activate different forelimb muscuJ Neurophysiol • VOL lature than those of RNp. Stimulation of fibers from RNm activated muscles of the distal limb (edc, pl, and ecu) more strongly than muscles of the proximal limb and shoulder (tr and ss). Stimulation of fibers from RNp activated muscles of the proximal limb and shoulder more strongly than those of the distal limb. Therefore the physiological actions of RNm and RNp are consistent with the anatomical observation that RNm fibers terminate more heavily at lower cervical segments and RNp fibers at upper segments (Pong et al. 2002). Patterns of activation Stimulation within the RN produces a highly characteristic pattern of StTAs. Digit (edc) and wrist (ecu) extensor muscles are strongly facilitated, whereas other limb muscles often show instances of suppression as well as facilitation. There are no other reports of StTAs resulting from stimulation of the cat RN, but stimulation in the monkey produces similar effects (Belhaj-Saif et al. 1998; Mewes and Cheney 1991). Digit and wrist extensor muscles are strongly facilitated, and several limb muscles show a high incidence of suppression (especially pl). 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 FIG. 5. Reconstruction of a stimulating track in the medulla. Stimulation above and below the RST failed to produce significant StTAs, whereas stimulation within the RST produced significant StTAs (heavier traces). The lower schematic illustrates the relative positions of fibers from RNm (RST-m) and RNp (RST-p) at the same brain stem level as that of the stimulating track. FUNCTIONAL SPECIALIZATION WITHIN THE RED NUCLEUS 475 Surprisingly, neither a favoring of edc nor a significant number of poststimulus suppressions occurred with stimulation of the RST. At medullary levels, RST stimulation produced a high probability of facilitation for all seven muscles (range 55–90% facilitation), and poststimulus suppression was limited to one muscle at one site. The lack of preferential facilitation of edc from the RST stimulation is especially surprising, since motor pools at C8 receive a selective input from the RN for the cat and monkey (Fujito et al. 1991; Holstege and Tan 1988; McCurdy et al. 1987; Ralston et al. 1988). However, most RN projections to the cord terminate in interneuronal regions rather than in motoneuronal pools, and it may be that the motoneuronal projections account for a relatively small portion of the poststimulus J Neurophysiol • VOL effects. If this is the case, why does stimulation within RN favor edc? One possibility is that input to edc (and other digit muscles) might arise from RN neurons with larger dendritic fields. Input to C7–C8 motoneuronal pools arises from the caudal RNm (Pong et al. 2002), which contains the largest cells in the nucleus. The dendritic fields of the large cells extend over a substantial portion of the nucleus in both cat and monkey (Burman et al. 2000; Condé and Condé 1973; Wilson et al. 1987), and stimulation in the nucleus could favor these cells. Afferents to the nucleus might also favor neurons projecting to edc, and stimulation anywhere within the nucleus could activate these afferents. The large dendritic fields of RNm neurons and fiber activation might contribute also to the failure to find 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 FIG. 6. Summary of muscle activation at different stimulation sites. Poststimulus facilitation is indicated as a positive percentage, whereas poststimulus suppression is indicated as a negative percentage. A: histogram indicating percentage of the significant StTA sites in the RNm of 3 cats. RNm stimulation most frequently facilitated edc and often produced suppression in other forelimb muscles. B: results of stimulation in RNp for 2 cats. The patterns of muscle activation were similar to RNm stimulation, although 2 shoulder muscles (sd and ss) were facilitated more frequently. C: stimulation in the dorsal half of the RST at mesencephalic levels frequently activated edc but not ss or sd. D: stimulation in the ventral half of the RST at mesencephalic levels frequently activated ss and sd but not edc. Stimulation in the dorsal (E) and ventral (F) halves of the RST at medullary levels activated all muscles with a relatively high probability. 476 HORN, PONG, BATNI, LEVY, AND GIBSON a significant difference in the pattern of muscle activation when stimulating within RNm and RNp. Poststimulus suppression Functional considerations Although the RN can influence all forelimb muscles, the emphasis on activation of distal muscles is supported by many lines of evidence. RN cells fire especially well during digit extension (Gibson et al. 1985, 1994; Jarratt and Hyland 1999; van Kan and McCurdy 2001). Cells in interpositus, the major input to RNm, discharge only if hand movements are included in the behavioral task (van Kan et al. 1994). Lesions of the RST most strongly affect digit use (Lawrence and Kuypers 1968; Schrimsher and Reier 1993; Sybirska and Gorska 1980; Whishaw and Gorny 1996), and temporary inactivation of RNm (Gibson et al. 1994) or interpositus (Mason et al. 1998; Milak et al. 1997) impairs the ability to properly position the digits for a variety of tasks such as grasping, walking, and standing. If the RN is specialized for control of distal musculature, why does stimulation of the RST produce postspike effects in proximal as well as distal muscles? Lesions or inactivation of the RN or lateral cerebellum impair the ability to position and maintain stability of the limb to support hand movements (Goldberger and Growdon 1973; Mason et al. 1998; Sybirska and Gorska 1980; Whishaw and Gorny 1996). It is likely that the RN helps coordinate proximal muscle activity with distal muscle activity to achieve a successful movement, such as grasping an object at the end of a reach or placing the foot properly for walking or standing. This work was supported by National Institute of Neurological Disorders and Stroke Grant NS-36820 (A. R. Gibson) and National Research Service Award NS-10726 (M. Pong). REFERENCES ALSTERMARK B, ISA T, KUMMEL H, AND TANTISIRA B. Projection from excitatory C3–C4 propriospinal neurones to lamina VII and VIII neurones in the C6-Th1 segments of the cat. Neurosci Res 8: 131–137, 1990. J Neurophysiol • VOL 87 • JANUARY 2002 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 Activation of synaptic mechanisms could account for the high incidence of poststimulus suppression seen with RN stimulation. Poststimulus suppression requires that some inhibitory mechanism be activated by the stimulation. Inhibitory mechanisms might be located within the RN, spinal cord, or at both locations. Intracellular recording from spinal motor neurons during RN stimulation indicates that only 6% of motor neurons at C6–C8 respond with inhibitory postsynaptic potentials (IPSPs) (Fujito et al. 1991). The percentage of IPSPs is too low to account for the 21% incidence of poststimulus suppression observed with RN stimulation. [Behaj-Saif et al. (1998) reported a 25% incidence of poststimulus suppression from RN stimulation in the monkey.] It is possible that poststimulus suppression results from activation of inhibitory synapses within the RN, which would not be activated by RST stimulation. There is evidence that the RN contains inhibitory interneurons as well as inhibitory afferents from a variety of sources (Katsumaru et al. 1984; Padel and Jeneskog 1981; Ralston and Milroy 1992; Vuillon-Cacciuttolo et al. 1984). BELHAJ-SAIF A, KARRER JH, AND CHENEY PD. Distribution and characteristics of poststimulus effects in proximal and distal forelimb muscles from red nucleus in the monkey. J Neurophysiol 79: 1777–1789, 1998. BERMAN AL. The Brain Stem of the Cat. Madison, WI: Univ. of Wisconsin Press, 1968. BURMAN K, DARIAN-SMITH C, AND DARIAN-SMITH I. Macaque red nucleus: origins of spinal and olivary projections and terminations of cortical inputs. J Comp Neurol 423: 179 –196, 2000. CHENEY PD AND FETZ EE. Comparable patterns of muscle facilitation evoked by individual corticomotoneuronal (CM) cells and by single intracortical microstimuli in primates: evidence for functional groups of CM cells. J Neurophysiol 53: 786 – 804, 1985. CHENEY PD, MEWES K, AND WIDENER G. Effects on wrist and digit muscle activity from microstimuli applied at the sites of rubromotoneuronal cells in primates. J Neurophysiol 66: 1978 –1992, 1991. CONDÉ F AND CONDÉ H. Study of the morphology of the cells of the red nucleus of the cat by the Golgi-Cox method. Brain Res 53: 249 –271, 1973. FETZ EE AND CHENEY PD. Postspike facilitation of forelimb muscle activity by primate corticomotoneuronal cells. J Neurophysiol 44: 751–772, 1980. FUJITO Y, IMAI T, AND AOKI M. Monosynaptic excitation of motoneurons innervating forelimb muscles following stimulation of the red nucleus in cats. Neurosci Lett 127: 137–140, 1991. GIBSON AR, HORN KM, AND VAN KAN PLE. Grasping cerebellar function. In: Insights into the Reach to Grasp Movement, edited by Bennet KMB and Castiello U. Amsterdam: Elsevier, 1994, p. 85–108. GIBSON AR, HOUK JC, AND KOHLERMAN NJ. Magnocellular red nucleus activity during different types of limb movement in the macaque monkey. J Physiol (Lond) 358: 527–549, 1985. GOLDBERGER ME AND GROWDON JH. Pattern of recovery following cerebellar deep nuclear lesions in monkeys. Exp Neurol 39: 307–322, 1973. HOLSTEGE G AND TAN J. Projections from the red nucleus and surrounding areas to the brainstem and spinal cord in the cat. An HRP and autoradiographical tracing study. Behav Brain Res 28: 33–57, 1988. JARRATT H AND HYLAND B. Neuronal activity in rat red nucleus during forelimb reach-to-grasp movements. Neuroscience 88: 629 – 642, 1999. KATSUMARU H, MURAKAMI F, WU JY, AND TSUKAHARA N. GABAergic intrinsic interneurons in the red nucleus of the cat demonstrated with combined immunocytochemistry and anterograde degeneration methods. Neurosci Res 1: 35– 44, 1984. LAWRENCE DG AND KUYPERS HG. The functional organization of the motor system in the monkey. II. The effects of lesions of the descending brain-stem pathways. Brain 91: 15–36, 1968. MASON CR, MILLER LE, BAKER JF, AND HOUK JC. Organization of reaching and grasping movements in the primate cerebellar nuclei as revealed by focal muscimol inactivations. J Neurophysiol 79: 537–554, 1998. MCCURDY ML, HANSMA DI, HOUK JC, AND GIBSON AR. Selective projections from the cat red nucleus to digit motor neurons [published erratum appears in J Comp Neurol 273: 445, 1988]. J Comp Neurol 265: 367–379, 1987. MILAK MS, SHIMANSKY Y, BRACHA V, AND BLOEDEL JR. Effects of inactivating individual cerebellar nuclei on the performance and retention of an operantly conditioned forelimb movement. J Neurophysiol 78: 939 –959, 1997. MEWES K AND CHENEY PD. Facilitation and suppression of wrist and digit muscles from single rubromotoneuronal cells in the awake monkey. J Neurophysiol 66: 1965–1977, 1991. PADEL Y AND JENESKOG T. Inhibition of rubro-spinal cells by somesthetic afferent activity. Neurosci Lett 21: 177–182, 1981. PONG M, HORN KM, AND GIBSON AR. Spinal projections of the cat parvicellular red nucleus. J Neurophysiol 87: 453– 468, 2002. RALSTON DD AND MILROY AM. Inhibitory synaptic input to identified rubrospinal neurons in Macaca fascicularis: an electron microscopic study using a combined immuno-GABA-gold technique and the retrograde transport of WGA-HRP. J Comp Neurol 320: 97–109, 1992. RALSTON DD, MILROY AM, AND HOLSTEGE G. Ultrastructural evidence for direct monosynaptic rubrospinal connections to motoneurons in Macaca mulatta. Neurosci Lett 95: 102–106, 1988. ROBINSON FR, HOUK JC, AND GIBSON AR. Limb specific connections of the cat magnocellular red nucleus [published erratum appears in J Comp Neurol 259: 622, 1987]. J Comp Neurol 257: 553–577, 1987. SCHRIMSHER GW AND REIER PJ. Forelimb motor performance following dorsal column, dorsolateral funiculi, or ventrolateral funiculi lesions of the cervical spinal cord in the rat. Exp Neurol 120: 264 –276, 1993. FUNCTIONAL SPECIALIZATION WITHIN THE RED NUCLEUS SYBIRSKA E AND GORSKA T. Effects of red nucleus lesions on forelimb movements in the cat. Acta Neurobiol Exp 40: 821– 841, 1980. VAN KAN PL, GIBSON AR, AND HOUK JC. Movement-related inputs to intermediate cerebellum of the monkey [published erratum appears in J Neurophysiol 69: following table of contents, 1993]. J Neurophysiol 69: 74 –94, 1993. VAN KAN PL, HORN KM, AND GIBSON AR. The importance of hand use to discharge of interpositus neurones of the monkey [published erratum appears in J Physiol (Lond) 481: 811, 1994]. J Physiol (Lond) 480: 171–190, 1994. VAN KAN PLE AND MCCURDY ML. Role of primate magnocellular red nucleus 477 neurons in controlling hand preshaping during reaching to grasp. J Neurophysiol 85: 1461–1478, 2001. VUILLON-CACCIUTTOLO G, BOSLER O, AND NIEOULLON A. GABA neurons in the cat red nucleus: a biochemical and immunohistochemical demonstration. Neurosci Lett 52: 129 –134, 1984. WHISHAW IQ AND GORNY B. Does the red nucleus provide the tonic support against which fractionated movements occur? A study on forepaw movements used in skilled reaching by the rat. Behav Brain Res 74: 79 –90, 1996. WILSON CJ, MURAKAMI F, KATSUMARU H, AND TSUKAHARA N. Dendritic and somatic appendages of identified rubrospinal neurons of the cat. Neuroscience 22: 113–130, 1987. Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 11, 2017 J Neurophysiol • VOL 87 • JANUARY 2002 • www.jn.org