* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Dexterous Finger Movements in Primate Without Monosynaptic
Neuropsychology wikipedia , lookup
Holonomic brain theory wikipedia , lookup
Synaptogenesis wikipedia , lookup
Brain–computer interface wikipedia , lookup
Embodied language processing wikipedia , lookup
Caridoid escape reaction wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Feature detection (nervous system) wikipedia , lookup
Central pattern generator wikipedia , lookup
Eyeblink conditioning wikipedia , lookup
Metastability in the brain wikipedia , lookup
Activity-dependent plasticity wikipedia , lookup
Neurostimulation wikipedia , lookup
Neuroplasticity wikipedia , lookup
Neuroanatomy wikipedia , lookup
Single-unit recording wikipedia , lookup
Channelrhodopsin wikipedia , lookup
J Neurophysiol 92: 3142–3147, 2004. First published June 2, 2004; 10.1152/jn.00342.2004. Report Dexterous Finger Movements in Primate Without Monosynaptic Corticomotoneuronal Excitation Shigeto Sasaki,1,* Tadashi Isa,2,* Lars-Gunnar Pettersson,3,* Bror Alstermark,4,* Kimisato Naito,1 Kazuya Yoshimura,1 Kazuhiko Seki,2 and Yukari Ohki5 1 Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan; 2Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan; 3Institute of Physiology and Pharmacology, Department of Physiology, Göteborg University, 405 30 Göteborg, Sweden; 4Department of Integrative Medical Biology, Section of Physiology, Umeå University, 901 87 Umeå, Sweden; and 5Department of Integrative Physiology, Kyorin University School of Medicine, Shinkawa, Tokyo 181-8611, Japan Submitted 2 April 2004; accepted in final form 25 May 2005 Kuypers showed that pyramidotomy caused near permanent loss of the precision grip and of independent finger movements (IFMs) of the hand (Lawrence and Kuypers 1968a,b). Transection of the rubrospinal tract (RST) after pyramidotomy aggravated the symptoms, suggesting a role also for the RST. It has later been shown that after pyramidotomy, some recovery may occur after ⬃1 yr (for references, see Porter and Lemon 1993). To test the role of the direct and indirect CM pathways, we have now made lesions of the CST in the lateral funicle at the border of the C4–C5 segments (C4/C5), which is just rostral to the forelimb MNs. METHODS Behavioral test Three female monkeys (Macaca fuscata), body weight 5.35, 4.75, and 4.5 kg, were trained to retrieve a morsel of food from a horizontal tube positioned in the mid-sagittal plane, at shoulder level and at a sagittal distance of 15 cm. Each experiment (30 min) consisted of ⬃100 trials. In each trial, the animal retrieved, with the precision grip, a morsel of food positioned on a pin that was inserted through the bottom of the tube. The movements were filmed with standard video cameras (33 Hz) positioned above, below, and on the side of the performing limb. Surgery INTRODUCTION Much of the motor cortical research in primates is devoted to the monosynaptic excitatory connection from the corticospinal tract (CST) to motoneurons (MNs) that appears weakly in primates such as the squirrel monkey and becomes gradually stronger in the macaque and cebus monkeys, chimpanzee, and orangutan to reach a peak in man (Kuypers 1981; Phillips and Porter 1971; Porter and Lemon 1993; Shapovalov 1975). Because the ability to perform skilled finger movements with the hand has likewise increased during development, it was suggested that the monosynaptic corticomotoneuronal (CM; henceforth referred to as direct CM) connection might play a decisive role in this control (Bernhard and Bohm 1954). In behavioral experiments in the macaque monkey, Lawrence and * These authors contributed equally to this work Address for reprint requests and other correspondence: B. Alstermark, Dept. of Integrative Medical Biology, Section of Physiology, Umeå University, S-901 87 Umeå, Sweden (E-mail: [email protected]). 3142 The animals were first anesthetized with ketamine (0.3 ml) and Xylazine (0.6 ml) and then with pentobarbital sodium (Nembutal, 60 mg/kg). The border between the C4 and C5 segments was exposed by a laminectomy, and a transverse opening was made in the dura. The CST lesion was made under a surgical microscope, in three steps.1) A small opening in the pia mater was made at the lateral convexity of the spinal cord. A horizontal strip in mediolateral direction of the lateral funicle was then made by inserting a minute hook into the opening. The hook was prepared from a 0.4 mm (OD) cannula. The tip (0.5 mm) was first bent (with fine pliers) at a right angle to assume the shape of a hook. To provide stability during insertion into the spinal cord, the cannula was bent a second time, at a right angle 5 mm from the tip. In other words, the cannula assumed an L-shape with a small hook at the tip. In this way, the proximal part of the cannula could be held firmly by a small surgical clamp during insertion of the tip into the spinal cord. In addition, bending the cannula a second time assured that the hook could not be inserted ⬎5 mm deep, which corresponds 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. 0022-3077/04 $5.00 Copyright © 2004 The American Physiological Society www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 17, 2017 Sasaki, Sigeto, Tadashi Isa, Lars-Gunnar Pettersson, Bror Alstermark, Kimisato Naito, Kazuya Yoshimura, Kazuhiko Seki, and Yukari Ohki. Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation. J Neurophysiol 92: 3142–3147, 2004. First published June 2, 2004; 10.1152/jn.00342.2004. It is generally accepted that the precision grip and independent finger movements (IFMs) in monkey and man are controlled by the direct (monosynaptic) corticomotoneuronal (CM) pathway. This view is based on previous observations that pyramidotomy causes near permanent deficits of IFMs. However, in addition to the direct CM pathway, pyramidotomy interrupts several corticofugal connections to the brain stem and upper cervical segments. Indirect (oligosynaptic) CM pathways, which are phylogenetically older, have been considered to be of little or no importance in prehension. In three adult macaque monkeys, complete transection of the direct CM pathway was made in C4/C5, which is rostral to the forelimb segments (C6– Th1). Electrophysiological recordings revealed lack of the direct lateral corticospinal tract (LCST) volley, monosynaptic extracellular field potentials in the motor nuclei, and monosynaptic CM excitation. However, a disynaptic volley, disynaptic field potentials and disynaptic CM excitation mediated via C3–C4 propriospinal neurons remained after the lesion. Thus the lesion interrupted the monosynaptic CM pathway and oligosynaptic LCST pathways mediated by interneurons in the forelimb segments. Precision grip and IFMs were observed already after 1–28 days postoperatively. Weakness in force and deficits in preshaping remained for an observation period of 3 mo. Indirect CM pathways may be important for neuro-rehabilitation. Report DEXTEROUS FINGER MOVEMENTS WITHOUT MONOSYNAPTIC CORTICOMOTONEURONAL EXCITATION 3143 to the distance from the lateral convexity of the spinal cord to the midline. 2) The dorsal part of the lateral funicle was transected, with watch maker’s forceps, from the dorsal root entry zone ventrally to the level of the horizontal strip lesioned in step 1. 3) The lesion was extended ventrally, with watch maker’s forceps, at the most lateral part of the lateral funiculus. During surgery, the direct descending corticospinal volley, evoked by transcranial magnetic stimulation, was recorded from the dorsal part of the lateral funiculus in C5 before and after the lesion (in monkeys I and G, not illustrated). The opening of the dura mater was closed by a substitute (Preclude, Gore and Associates). The skin and back muscles were sutured with nylon or silk thread. Electrophysiological experiments RESULTS Figure 1A illustrates the maximal extent of C4/C5 lesions (black area) in three monkeys (Y, I, and G). The lesions covered the area of normal distribution (Kuypers 1981; Porter and Lemon 1993) of CS fibers (Y) or were larger than this area (I and G). To assess the C4/C5 lesions, electrophysiological recordings were made caudally. Figure 1B shows recordings from the spinal half at mid thoracic level on the intact and lesioned sides. On the intact side, electrical stimulation of the contralateral pyramid (co Pyr) evoked a direct CS volley followed, with a delay of ⬃1.2 ms, by a synaptic volley. The latter volley is presumably caused by monosynaptic Pyr actiJ Neurophysiol • VOL FIG. 1. Control of corticospinal tract (CST) lesion in C4–C5. A: histological reconstruction of the spinal cord lesions in 3 different monkeys (Y, I, G). B: the effect of stimulating the contralateral pyramid (Pyr) electrically (200 A) and recording from dissected spinal halves at thoracic level on the intact side (top) and on the lesioned side (bottom). Solid vertical line, the onset of the direct CST volley (lacking on the lesioned side); dashed line, the onset of the synaptic CST volley (present on both sides). C: recordings of extracellular synaptic field potentials (top) in the motor nuclei and the cord dorsum potentials (bottom) evoked by electrical stimulation of the contralateral Pyr. Filled arrow, the direct CST volley on the intact side. Open arrow, the monosynaptic pyramidal field in the motor nuclei on the intact side. Arrowheads, the disynaptic field potential in the motor nuclei on either side. vation of neurons with long descending axons. In contrast, on the lesioned side, the direct CS volley was completely abolished (solid line), while the synaptic volley (interrupted line) remained (mediated by descending axons in an intact funicle). Extracellular recordings of field potentials were made in the lateral motor nuclei in C6–C8 (a train of 3 stimuli were applied to the pyramid) as illustrated for the intact and lesioned sides (Fig. 1C). After a delay of 0.3 ms from the direct CS volley (filled arrow), a negative field potential (open arrow and solid line) was recorded (top) on the intact side. This potential is due to extracellular currents, which generate monosynaptic CM excitatory postsynaptic potentials (EPSPs) in forelimb MNs. On the lesioned side (Fig. 1C bottom), this field was lacking. However, already the first Pyr stimulus evoked a later (1.2 ms) small synaptic field (arrow head), which most likely is due to disynaptic CM excitation evoked in forelimb MNs. On the lesioned side this field was slightly facilitated by the second and third Pyr volleys. On the intact side (Fig. 1C), a similar field potential was recorded (arrow head), which was markedly facilitated by the second and third Pyr volleys. The latency to the onset of the disynaptic field was similar on the intact and lesioned sides (interrupted line). Similar electrophysiological results were obtained in the three monkeys. 92 • NOVEMBER 2004 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 17, 2017 The animals were first anesthetized with ketamine (0.3 ml) and Xylazine (0.6 ml) and after the tracheotomy, isofluorane was used throughout the surgery. After surgery, anesthesia was changed to ␣-chloralose 75–100 mg/kg. Blood pressure was maintained around 100 mmHg and pCO2 at 4.0%. A drip of Ringer-glucose was given during the entire experiment, and the urinary bladder was emptied regularly. Atropin (0.5 mg), decadrone (4 mg), gentacine (1 ml) were given just after anesthesia. Atropin was given at intervals of 4 –5 h. The animals were paralyzed with pancuronium bromide (Myoblock 1 ml, 0.2 mg/ml) given at 30-min interval and artificially ventilated with a pump. A pneumothorax was made just prior to intracellular recording. A craniotomy was made that exposed the posterior part of cerebellum and the caudal brain stem to place the pyramidal electrode. It was calibrated at the obex (angle 65° from the vertical line) and placed ⬃2.5 mm rostrally and 1.25 mm laterally and at depth of 5.0 mm from the bottom of IVth ventricle. The threshold for eliciting the descending pyramidal volley was usually ⬃5 A. Monopolar cathodal pulses (0.1-ms duration) were applied by using tungsten electrodes with an impedance ⬃50 –100 k⍀ and a tip diameter of 10 m. A laminectomy was made of the C2–Th1 and of the Th6–Th10 segments. The DR nerve was dissected and mounted in a cuff with bipolar silver electrodes. Other forelimb nerves were stimulated with inserted needle electrodes through the skin. Bipolar recordings of the descending volleys were made from dissected spinal halves in the Th6–Th10 segments as described before (Alstermark et al. 1981). Intracellular recordings were made from antidromically identified forelimb MNs (and unidentified MNs) in the lateral motor nuclei of the C6–Th1 segments. Glass capillary electrodes (tip diameter: ⬃1.0 m, impedance: ⬃3–5 M⍀) filled with 2 M potassium citrate were used. The cord dorsum potential was monitored with a silver ball electrode. The experiments were subjected to prior ethical reviews by the ethical committee of the Okazaki Organization of National Institutes and were performed in accordance with the National Institutes of Health guideline for the Care and Use of Laboratory Animals. Report 3144 SASAKI ET AL. is shown in Fig. 3A. In monkey Y, the precision grip was present already the first postoperative day (Fig. 3B). The preshaping prior to contact with the morsel was reduced. The aperture between the finger tips was smaller than the thickness of the morsel, and it was common that the thumb hit the posterior part of the morsel. Then the monkey widened the aperture, and the thumb was positioned on the side of the morsel allowing a precision grip by flexion of the proximal interphalangeal joint of the index finger and opposing movement of the thumb (Fig. 4A). Compared with the preoperative movement, it was common that the digits slipped during removal presumably due to low grip force so that more than one attempt was required. Another difference from the preoperative state was that the duration of the movement was substantially increased as is evident from the time-lines in Fig. 3, A–C (postoperative day 7). These defects became gradually less pronounced but remained to the end of the observation period (3 mo). A decreased force and slowing of the movement was also found after pyramidotomy and after cervical hemisection of the spinal cord (Galea and Darian-Smith 1997). Prehension improved markedly during the first postoperative week. On the 7th postoperative day (Fig. 3C), the placement of the index finger and thumb on the morsel closely resembled the preoperative one. Postoperatively, it was evident in some trials already in the first experiments in monkey Y, that the thumb during preshaping could be moved without concomitant movements of digits 3–5. During the two first postoperative weeks, the ability to perform independent finger movements improved, and in several trials, the extension of the index finger during preshaping was not accompanied by parallel extension of the other digits. Figure 4D shows superimposed stick figures of the index finger (D2) and of digit 5 (D5) viewed from the lateral side at the time of contact with the morsel. When the index finger was flexed during removal of the morsel, there was always parallel flexion of digit 5. This was the case throughout a postoperative observation period of 3 mo in the three monkeys. FIG. 2. Pyramidal effects in forelimb motoneurons (MNs). A–C: the effect of coPyr stimulation in a deep radial (DR) MN recorded intracellularly (top) on the intact side monkey G. Bottom: traces were recorded from the cord dorsum in the same segment as the motoneurone and show the direct CST volley followed by a synaptic volley. D–F: the effect of coPyr stimulation in another DR MN recorded intracellularly (top) on the lesioned side monkey G. The cord dorsum recording showed the absence of the direct CST volley, but the presence of the synaptic volley. The onset of a disynaptic excitatory postsynaptic potential (EPSP) is indicated in D (1). In F, 2 shows the onset of a presumed trisynaptic inhibitory postsynaptic potential (IPSP), which starts at the peak of the disynaptic EPSP. G: averaged traces from the records shown in A and D, respectively. The stimulus artifacts have been removed from the traces. Interrupted line, the onset of the disynaptic IPSP in A and the disynaptic EPSP in D.1, the latency difference between the mono- and disynaptic EPSP recorded from the intact and lesioned sides, respectively. H: latency histogram of coPyr EPSPs (from the 3rd volley) in forelimb MNs recorded in the C6–C8 segments. Latency measurements are made from the incoming direct CST volley on the intact side. J Neurophysiol • VOL 92 • NOVEMBER 2004 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 17, 2017 Intracellular recording was made from a total of 59 forelimb MNs in C6–C8 in the three animals on the intact (n ⫽ 22) and lesioned (n ⫽ 37) sides. Pyr stimulation evoked EPSPs in all MNs on the intact side (IPSP were recorded in 4 cells) and in 18 MNs on the lesioned side (IPSPs were seen in 9 cells). Measurements of the latency from the arrival of the descending CS volley to the onset of the EPSPs (Fig. 2H) showed a monosynaptic range (from 0.4 to 1.0 ms) on the intact side (white area), but a disynaptic range (1.0 –1.8 ms) in 15 cells on the lesioned side (black area) and possibly a trisynaptic range (from 1.8 to 2.0 ms) in 3 cells. Figure 2, A–C, shows intracellular recordings from a deep radial motoneuron on the intact side. A single Pyr stimulus (A) evoked a monosynaptic EPSP, which was cut by a disynaptic IPSP (see G,2). On the lesioned side (Fig. 2, D–F), recordings from another deep radial motoneuron show that Pyr stimulation failed to evoke a monosynaptic EPSP. However, even a single pyramidal stimulation evoked a disynaptic EPSP (D,1). After the second and third Pyr volleys, the EPSP was slightly facilitated and was followed by an IPSP (F, 2), which started at the peak of the EPSP. Figure 2G shows a comparison of the averaged traces of the EPSPs evoked by a single stimulus on the intact (A) and lesioned (D) sides. The EPSP evoked in the motoneuron on the lesioned side starts 0.9 ms later than the EPSP in the motoneuron on the intact side, corresponding to one intercalated neuron. Note that the onset of the IPSP (G, 2; intact side) was similar as for the EPSP of the lesioned side, with a disynaptic linkage in both cases. Based on these electrophysiological results, in addition to the histological controls (Fig. 1), we conclude that the CST lesions in the three monkeys were complete but that disynaptic Pyr excitation could still be evoked in forelimb MNs on the lesioned side. The ability to take a morsel of food with a precision grip was tested as shown in Fig. 3 (A–C, view from above and D from below) with video frames and in Fig. 4 (A–C, top view) with stick figures of the index finger and thumb. A preoperative trial Report DEXTEROUS FINGER MOVEMENTS WITHOUT MONOSYNAPTIC CORTICOMOTONEURONAL EXCITATION 3145 Independent finger movements were present regularly on the 9th postoperative day in monkey Y (smallest lesion), on the 25th day in monkey I, and on the 28th day in monkey G. DISCUSSION The fast and surprisingly good recovery observed in all three monkeys of this study is in clear contrast to previous investigations (Galea and Darian-Smith 1997; Lawrence and Kuypers 1968a,b). After complete pyramidotomy, independent finger movements were abolished for the whole observation period of ⱕ11 mo (Lawrence and Kuypers 1968a). In contrast, although all our monkeys showed deficits in preshaping and force between the index finger and thumb, they could grasp the morsel of food by using independent finger movements after 1–28 days postoperatively. Because the present lesions abolished both monosynaptic CM excitation as well as excitation mediated via segmental interneurons (below C5), we conclude that these pathways are not solely responsible for fine finger control as has been taken for granted during several decades especially for the monosynaptic excitatory CM connection. However, deficits in force and preshaping of the index finger and thumb prior to grasping were clearly evident after the lesions and are most likely dependent on the monosynaptic CM pathway. J Neurophysiol • VOL It is indeed remarkable that the command for precision grip and independent digit movements can be mediated via nonmonosynaptic CM pathways. A comparison with the location of the RST (Holstege et al. 1988) suggests an incomplete RST lesion in monkey Y but not in monkeys I and G. One possibility is that the modest effect of the lesion in monkey Y on the precision grip is due to a RST takeover. It is noteworthy that 60% of the RS neurons are activated during grasping of food from small holes in the Klüver test (Miller et al. 1993). A reorganization of the RS output to forearm muscles was found after pyramidotomy, such that the normally predominant extensor excitation and flexor suppression was diminished (Belhaj-Saif and Cheney 2000). As an alternative to an RST takeover, the possible role of propriospinal neurons (PNs) should be considered. It was recently shown that disynaptic CM EPSPs in the macaque monkey can be mediated via PNs in the C3–C4 segments (Alstermark et al. 1999). This system was first described in the cat (Illert et al. 1977), which lacks monosynaptic CM connections. In the macaque monkey, the C3–C4 PNs are under strong inhibitory control, and disynaptic EPSPs were found regularly only after intravenous injection of strychnine (Alstermark et al. 1999). In the present study, disynaptic CM EPSPs could be induced even without strychnine in half of the forelimb MNs 92 • NOVEMBER 2004 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 17, 2017 FIG. 3. Prehension movements in monkey Y, preoperatively (A) and at postoperative day 1 (B) and 7 (C and D). A–C: the view from above and D the view from below. The time intervals (ms) relative to the leftmost image are indicated in the top right corner of the digitized video images. Report 3146 SASAKI ET AL. after the CS lesion in C4/C5, occasionally even by a single stimulus (Fig. 2D). It is postulated that the strength of inhibition has decreased so that C3–C4 PNs mediating disynaptic EPSPs are more readily activated after a chronic CST lesion. Enhanced propriospinal excitation of upper limb MNs was found in stroke patients (Mazevet et al. 2003). In monkeys I and G (Fig. 1A), the lesions extended more ventrally than in monkey Y and probably completely transected the RST. However, it is unlikely that these lesions have transected a significant part of the axons of the C3–C4 PNs because intracellular recording from forelimb MNs confirmed that disynaptic Pyr EPSPs could be evoked in all three monkeys, and threshold mapping of the axons of C3-C4 PNs has shown that they surround the ventral horn and extend ventromedially to the base (Alstermark and Isa, unpublished data). Furthermore, in monkey G, we added an acute transection of the CST in C2 (not illustrated), where after disynaptic CM EPSPs were abolished in six of six tested MNs, which shows that disynaptic Pyr EPSPs indeed could be mediated via C3–C4 PNs despite the larger lesion. In the cat, C3–C4 PNs mediate the command for forelimb target reaching, while the command for grasping with the forepaw is mediated by interneurons in the forelimb segments (Alstermark et al. 1981). However, recently Blagovechtchenski et al. (2000) found that after combined spinal cord lesions (CST⫹RuST in C5 and ventral quadrant lesion in C2) the C3–C4 PNs can mediate the command for some components of grasping like flexion in the proximal interphalangeal joints, but not supination and flexion in the metacarpophalangeal joints by J Neurophysiol • VOL which intact cats bring the morsel of food to the mouth. It may be hypothesized that evolution has given the C3–C4 PN system a new or additional role in primates to command the precision grip in relation to reaching. This may explain why the precision grip and independent digit movements remain after transection of the CST. There is some evidence from cortical lesions which may support a C3–C4 PN takeover. Some CS fibers originate in the premotor (PM) area and terminate in the C2–C4 segments (Martino and Strick 1987). The recovery of manual dexterity after lesion of the hand area in MI was abolished by reversible inactivation of PM (Liu and Rouiller 1999). The recovery after the MI lesion was very slow and incomplete. Structural reorganization in PM has been observed after M1 lesion (Frost et al. 2003). Our findings suggest that the role of CM pathways in commanding the precision grip and independent digit movements must be broadened and include not only the direct connection but also indirect ones. Transmission is apparently so effective that the precision grip and independent finger movements can be made within a day (monkey Y) even if the monosynaptic CM connection (and to segmental interneurons) is broken. The fact that interneuronal networks exist may be important for neuro-rehabilitation. Physiotherapy must aim at mobilizing these networks, and such a mobilization may explain the recovery of the precision grip and independent digit movements that may be observed in humans after complete interruption of the CM pathways in the brain stem (Bach-y-Rita 1981). 92 • NOVEMBER 2004 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 17, 2017 FIG. 4. Stick figure representation of prehension movements preoperatively and at the postoperative days indicated in monkey Y. A: the moment of 1st tactile contact between the index finger and the morsel. B: the moment of entry of the thumb into the tube. C: precision grip of the morsel between the thumb and the index finger. The last frame before onset of removal of the morsel from the pin. Blue lines represent the index finger and red lines the thumb. The following positions are indicated for the index finger: the metacarpophalangeal joint (MCP), the proximal interphalangeal joint (PIP), the distal interphalangeal joint (DIP) and the finger tip. For the thumb: MCP, DIP and the finger tip. D: stick figure of prehension movements from the 7th postoperative day. The positions of the MCP, PIP, and DIP joints are indicated as well as the tips of the digits. The index finger (D2 in blue) and digit 5 (D5 in red) are superimposed. The digits have been aligned at the position of the PIP joint. Report DEXTEROUS FINGER MOVEMENTS WITHOUT MONOSYNAPTIC CORTICOMOTONEURONAL EXCITATION ACKNOWLEDGMENTS We thank A. Lundberg for stimulating discussions about the manuscript, S. Kumagai, M. Mori, and Y. Morichika for taking care of the monkeys, and M. Seo for histology. GRANTS This work was funded by a grant from the Human Frontier Science Program. REFERENCES J Neurophysiol • VOL Holstege G, Blok BF, and Ralston DD. Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey. Neurosci Lett 95: 97–101, 1988. Illert M, Lundberg A, and Tanaka R. Integration in descending motor pathways controlling the forelimb in the cat. III. Convergence on propriospinal neurones transmitting disynaptic excitation from the corticospinal tract and other descending tracts. Exp Brain Res 29: 323–346, 1977. Kuypers HGJM. The organization of the motor system in primates. In: Handbook of Physiology. The Nervous System. Motor Control. Bethesda, MD: Am. Physiol. Soc., 1981, sect. 1, vol. 2, p 623– 634. Lawrence DG and Kuypers HG. The functional organization of the motor system in the monkey. I. The effect of bilateral pyramidal lesions. Brain 91: 1–14, 1968a. 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, 1968b. Liu Y and Rouiller EM. Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys. Exp Brain Res 128: 149 –159, 1999. Martino AM and Strick PL. Corticospinal projections originate from the arcuate premotor area. Brain Res 404: 307–312, 1987. Mazevet D, Meunier S, Pradat-Diehl P, Marchand-Pauvert V, and Pierrot-Deseilligny E. Changes in propriospinally mediated excitation of upper limb motoneurons in stroke patients. Brain 126: 988 –1000, 2003. Miller LE, van Kan PL, Sinkjaer T, Andersen T, Harris GD, and Houk JC. Correlation of primate red nucleus discharge with muscle activity during free-form arm movements. J Physiol 469: 213–243, 1993. Phillips CG and Porter R. Corticospinal neurons. Their role in movement. Monogr Physiol Soc 34: 1– 450, 1971. Porter R and Lemon R. Corticospinal function and voluntary movement. Monogr Physiol Soc 45: 1– 428, 1993. Shapovalov AI. Neuronal organization and synaptic mechanisms of supraspinal motor control in vertebrates. Rev Physiol Biochem Pharmacol 72: 2–54, 1975. 92 • NOVEMBER 2004 • www.jn.org Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 17, 2017 Alstermark B, Isa T, Ohki Y, and Saito Y. Disynaptic pyramidal excitation in forelimb motoneurons mediated via C3-C4 propriospinal neurons in the Macaca fuscata. J Neurophysiol 82: 3580 –3585, 1999. Alstermark B, Lundberg A, Norrsell U, and Sybirska E. Integration in descending motor pathways controlling the forelimb in the cat. IX. Differential behavioral defects after spinal cord lesions interrupting defined pathways from higher centers to motoneurons. Exp Brain Res 42: 299 –318, 1981. Bach-y-Rita P. Brain plasticity as a basis of the development of rehabilitation procedures for hemiplegia. Scand J Rehab Med 13: 73– 83, 1981. Belhaj-Saif A and Cheney PD. Plasticity in the distribution of the red nucleus output to forearm muscles after unilateral lesions of the pyramidal tract. J Neurophysiol 83: 3147–3153, 2000. Bernhard CG and Bohm E. Cortical representation and functional significance of the corticomotoneuronal system. Arch Neurol Psych 72: 473–502, 1954. Blagovechtchenski E, Pettersson L-G, Perfiliev S, Krasnochokova, and Lundberg A. Control of digits via C3-C4 propriospinal neurons in cats: recovery after lesions. Neurosci Res 38: 103–107, 2000. Frost SB, Barbay S, Friel KM, Plautz EJ, and Nudo RJ. Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. J Neurophysiol 89: 3205–3214, 2003. Galea MP and Darian-Smith I. Manual dexterity and corticospinal connectivity following unilateral section of the cervical spinal cord in the macaque monkey. J Comp Neurol 381: 307–319, 1997. 3147