Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons.

In motor control, the general view is still that spinal interneurons mainly contribute to reflexes and automatic movements. The question raised here is whether spinal interneurons can mediate the cortical command for independent finger movements, like a precision grip between the thumb and index finger in the macaque monkey, or if this function depends exclusively on a direct corticomotoneuronal pathway. This study is a followup of a previous report (Sasaki et al. J Neurophysiol 92: 3142-3147, 2004) in which we trained macaque monkeys to pick a small piece of sweet potato from a cylinder by a precision grip between the index finger and thumb. We have now isolated one spinal interneuronal system, the C3-C4 propriospinal interneurons with projection to hand and arm motoneurons. In the previous study, the lateral corticospinal tract (CST) was interrupted in C4/C5 (input intact to the C3-C4 propriospinal interneurons), and in this study, the CST was interrupted in C2 (input abolished). The precision grip could be performed within the first 15 days after a CST lesion in C4/C5 but not in C2. We conclude that C3-C4 propriospinal interneurons also can carry the command for precision grip.

The C3-C4 propriospinal system in the cat and monkey: a spinal pre-motoneuronal centre for voluntary motor control.

This review deals with a spinal interneuronal system, denoted the C3-C4 propriospinal system, which is unique in the sense that it so far represents the only spinal interneuronal system for which it has been possible to demonstrate a command mediating role for voluntary movements. The C3-C4 propriospinal neurones govern target reaching and can update the descending cortical command when a fast correction is required of the movement trajectory and also integrate signals generated from the forelimb to control deceleration and termination of reaching.

Skilled digit movements in feline and primate--recovery after selective spinal cord lesions.

Recovery of voluntary movements after partial spinal cord injury depends, in part, on a take-over of function via unlesioned pathways. Using precise forelimb movements in the cat as model, spinal pathways contributing to motor restitution have been investigated in more detail. The food-taking movement by which the cat graSPS a morsel of food with the digits and brings it to the mouth is governed by interneurones in the forelimb segments (C6-Th1) and is normally controlled via the cortico- and rubrospinal tracts. Food-taking disappears after transection of these pathways in the dorsal part of the lateral funiculus (DLF) in C5/C6, but then recovers during a period of 2-3 weeks. Experiments with double lesions showed that the recovery depends on a take-over via ipsilateral ventral systems; a ventrally descending pathway, most probably cortico-reticulospinal, and a pathway via propriospinal neurones in the C3-C4 segments. It is postulated that the recovery involves a plastic reorganization of these systems. Dexterous finger movements in the macaque monkey are generally considered to depend on the monosynaptic cortico-motoneuronal (CM) connexion, which is lacking in the cat. Such movements are abolished after pyramidotomy at the level of the trapezoid body. However, experiments with transection of the corticospinal tract in the DLF and partly ventral part of the lateral funiculus in C5, showed a fast (1-28 days) recovery of precision grip and, to some extent, independent finger movements. Deficits in preshaping during the final approach to the morsel as well as lack of force were observed. A C5 DLF lesion spares corticofugal pathways to the brainstem and upper cervical segments. It is suggested that indirect corticomotoneuronal pathways may provide for recovery of dexterous finger movements and that the role of CM pathways for such movements should be broadened to include not only the monosynaptic connexion.

Lack of monosynaptic corticomotoneuronal EPSPs in rats: disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons.

In the rat, some findings have been taken to suggest the existence of monosynaptic corticomotoneuronal (CM) connections. Because this connection is believed to be largely responsible for the ability to make independent digit movements in primates and man, it has been inferred that the monosynaptic CM connection in the rat is likewise important for skilled prehension. Comparison of intra- and extracellular recordings from forelimb motoneurons in anesthetized rats, revealed no monosynaptic CM excitatory postsynaptic potentials (EPSPs). The fastest descending excitation in forelimb motoneurons was disynaptically mediated via a corticoreticulospinal pathway and slowly conducted excitation via corticospinal fibers and segmental interneurons. The findings stress the importance of di- and trisynaptic excitatory corticofugal pathways to forelimb motoneurons in the control of skillful digit movements.

Interruption of a relay of corticospinal excitation by a spinal lesion at C6-C7.

In a patient with a limited lesion of the spinal cord at the C6-C7 junction, ulnar and superficial radial-induced modulations of the motor evoked potentials (MEP) and of ongoing electromyographic (EMG) activity were observed in the biceps (above the lesion) but not in the triceps (below the lesion). This suggests an interruption of the axons of cervical propriospinal neurons. This relay transmits an indirect (disynaptic) component of corticospinal excitation to human upper limb motoneurons. Changes in it might be involved in compensatory mechanisms following central motor disorders.

Origin of corticospinal neurones evoking monosynaptic excitation in C3--C4 propriospinal neurones in the cat.

Intracellular recording was made from propriospinal neurones (PNs) in the C3-C4 spinal cord segments in the cat (alpha-chloralose anaesthesia). The effect of electrical stimulation of corticospinal neurones (CSNs) in the cortex was investigated. Short C3-C4 PNs were identified by antidromic activation of their axons in the ventral horn in C6/C7 and in the lateral reticular nucleus. Long PNs were antidromically identified from Th12-13. In short PNs, monosynaptic excitory postsynoptic potentials (EPSPs) were elicited from the rostral part of the lateral sigmoid gyrus, the lateral part of the anterior sigmoid gyrus in area 4 gamma and in the adjacent area 6. Two subtypes of short PNs were identified. PNs of type I received monosynaptic EPSPs from the rostral part of the lateral sigmoid gyrus, the lateral part of the anterior sigmoid gyrus in area 4 gamma, which is from the same region as disynaptic cortical EPSPs were evoked in forelimb motoneurones. PNs of type II received monosynaptic EPSPs from regions slightly more rostrally in the anterior sigmoid gyrus in area 4 gamma and in the adjacent area 6, which is outside the region from which disynaptic EPSPs could be evoked in forelimb motoneurones. Long PNs received monosynaptic EPSPs, like the short PNs, by stimulation in the rostral part of the lateral sigmoid gyrus, the lateral part of the anterior sigmoid gyrus in area 4 gamma and in the adjacent area 6. In contrast, the long PNs also received monosynaptic EPSPs from area 3b near the border of area 1. The present results show segregation of the cortical control to functionally different premotoneuronal systems and suggest that this control could in part be separated for subtypes of short C3-C4 PNs.

Origin of corticospinal neurones evoking disynaptic excitation in forelimb motoneurones mediated via C3-C4 propriospinal neurones in the cat.

Intracellular recording was made from forelimb motoneurones in the cat (alpha-chloralose anaesthesia) during electrical stimulation of corticospinal neurones (CSNs) and their afferents in the contralateral cortex. Axons of the CSNs were stimulated in the contralateral pyramid. The corticospinal tract was transected at the C5/C6 segmental border in order to restrict transmission through the C3-C4 propriospinal neurones (C3-C4 PNs). Di- and trisynaptic cortical EPSPs could be evoked after transection of the corticospinal fibres in C5/C6 but not after a corresponding transection in C2/C3. Pyramidal stimulation elicited disynaptic EPSPs that were abolished after a C2/C3 transection. Disynaptic pyramidal EPSPs, mediated via C3-C4 propriospinal neurones could be facilitated by a single cortical stimulation. It is concluded that di- and trisynaptic cortical EPSPs and disynaptic pyramidal EPSPs are mediated via the same C3-C4 PNs. Cortical surface stimulation showed that di- and trisynaptic cortical EPSPs could be evoked from distinct spots in the lateral part of the anterior sigmoid gyrus (Sig. a) and/or in the rostral part of the lateral sigmoid gyrus (Sig. l). No cortical EPSPs or facilitation of pyramidal disynaptic EPSPs was evoked from the posterior part of the Sig. l, posterior sigmoid gyrus, coronal gyrus, lateral gyrus, suprasylvian gyrus and ectosylvian gyrus. It is concluded that the CSNs, which issue the command for visually guided target reaching with the forelimb via the C3-C4 PNs, originate in the lateral part of the Sig. a and in the rostral part of the Sig. l. A dual representation of the forelimb in the primary motor cortex of the cat has previously been proposed. The present results show that with respect to one identified interneuronal system like the C3-C4 propriospinal system, the CSNs may have their origin restricted to one region of the primary motor cortex.

Disynaptic pyramidal excitation in forelimb motoneurons mediated via C(3)-C(4) propriospinal neurons in the Macaca fuscata.

In contrast to findings in the cat, it recently has been shown that disynaptic pyramidal EPSPs only rarely are observed in forelimb motoneurons of the macaque monkey in the intact spinal cord or after a corticospinal transection in C(5). This finding has been taken to indicate that the disynaptic pyramidal excitatory pathway via C(3)-C(4) propriospinal neurons (PNs) is weakened through phylogeny when the monosynaptic cortico-motoneuronal connection has been strengthened. We reinvestigate this issue with special focus on the possibility that the inhibitory control of the C(3)-C(4) PNs may be stronger in the macaque monkey than in the cat. The effect in forelimb motoneurons of electrical stimulation in the contralateral pyramid was investigated in anesthetized macaque monkeys (Macaca fuscata). We confirmed the low frequency of disynaptic pyramidal EPSPs in forelimb motoneurons. However, after intravenous injection of strychnine, disynaptic EPSPs could be evoked in 39 of 41 forelimb motoneurons recorded after lesion of the corticospinal fibers in C5. After a corresponding lesion in C(2), disynaptic pyramidal EPSPs were observed in 2 of 25 motoneurons. In contrast to previous reports, we conclude that C(3)-C(4) PNs can mediate disynaptic pyramidal excitation in high frequency of occurrence to forelimb motoneurons in the C(6)-C(8) segments and that this transmission is under a stronger inhibitory control than in the cat. Thus, the hypothesis that the disynaptic excitatory cortico-motoneuronal pathway via the C(3)-C(4) PNs is weakened in parallel with the strengthened monosynaptic connection through phylogeny is not supported by the present findings.

Effect of spinal cord lesions on forelimb target-reaching and on visually guided switching of target-reaching in the cat.

Cats were trained to reach to an illuminated tube placed horizontally at shoulder level and retrieve food with the forepaw. The trajectory of an infrared light emitting diode, taped to the wrist dorsum, was recorded with a SELSPOT-like recording system. Movement paths and velocity profiles were compared before and after lesions: (1) in dorsal C5, transecting cortico- and rubrospinal pathways to the forelimb segments so that the cats could only use the C3-C4 propriospinal neurones (PNs) to command reaching, (2) in the ventral part of the lateral funicle in C5, transecting the axons of C3-C4 PNs so that the cats had to use circuitry in the forelimb segments to command reaching. Comparison of trajectories and velocity profiles before and after lesion 1 did not reveal any major qualitative change. After lesion 2, the last third of the movement was fragmented with separate lifting and protraction. Switching of target-reaching occurred when illumination was shifted to another tube during the ongoing movement. The switching latency measured from the time of illumination shift to the earliest change in movement trajectory had a minimal value of 50-60 ms. Short latencies were present after lesion 1 as well as lesion 2 which suggest that fast switching mediated by the C3-C4 PNs and the interneuronal system in the forelimb segments is controlled in parallel by the brain. In order to test a hypothesis that fast switching depends on the tectospinal and tecto-reticulospinal pathways (the tecto-reticulo-spinal system) a ventral lesion was made in C2 aiming at interrupting these pathways. Large ventral C2 lesions tended to block conduction in the more dorsally located rubrospinal (less in corticospinal) axons probably due to compression during surgery. When conduction in the rubrospinal tract was completely interrupted by a ventral C2 lesion which also completely transected the axons of the tecto-reticulo-spinal system, then there was a prolongation of the switching latency with 10-20 ms. After a similar large ventral lesion with remaining conduction in the rubrospinal tract the switching latencies were unchanged. It is postulated that fast visually governed switching does not depend on the tecto-reticulo-spinal system alone but on more dorsally located pathways, presumably the rubrospinal tract, either acting alone or together with the tecto-reticulo-spinal system. It is further postulated that the delayed switching after interruption of conduction both in the rubrospinal tract and the tecto-reticulo-spinal system depends on the corticospinal tract. Visual control of rubrospinal and of corticospinal neurones is considered. It is postulated that target-reaching normally depends on signals in the cortico- and rubrospinal tracts and mechanisms for co-ordination of activity in them as required during switching is discussed in view of the findings now reported.

Motoneuronal projection pattern of single C3-C4 propriospinal neurones.

The pattern of motoneuronal projection and termination of single C3-C4 propriospinal neurones in the forelimb segments C6-T1 of the cat was investigated by intra-axonal injection of horseradish peroxidase into stem axons. Twelve well-stained axons were used for analysis. Termination was observed in the estimated location of motor nuclei innervating pure shoulder muscles in 10 cases. Among motoneurones innervating shoulder, elbow, wrist, and digit muscles, projection and termination were observed in motor nuclei controlling muscles of two or three joints in the following combinations: shoulder + elbow, shoulder + wrist, shoulder + elbow + wrist, shoulder + elbow + digit, and elbow + wrist + digit. In one case it was difficult to exclude the possibility of projection and termination in motor nuclei controlling muscles at all four joints. These patterns of motoneuronal projection from C3-C4 propriospinal neurones are compatible with their function in mediating the descending command for visually guided target reaching movements with the forelimb. In addition, it was found that the C3-C4 propriospinal neurones project and terminate in the region of ventral and ventromedial motor nuclei, which innervate axial muscles acting on the trunk. This was confirmed by intracellular recording from presumed ventromedial motoneurones in the C6-C7 segments. It is postulated that the C3-C4 propriospinal neurones, in addition to their control of forelimb movements, provide for conjoint control of axial muscles to stabilize the trunk during target reaching.

Characteristics of target-reaching in cats. I. Individual differences and intra-individual constancy.

Trajectory formation of unrestrained forelimb target-reaching was investigated in six cats. A Selspot-like recording system was used for three-dimensional recording of the position of the wrist every 3 ms with the aid of two cameras detecting infrared light emitted from diodes taped to the wrist. These measurements allowed reconstruction of movement paths in the horizontal and sagittal planes and velocity profiles in the direction of the cartesian x, y and z co-ordinates. Horizontal movement paths were smoothly curved, segmented or almost linear. Sagittal movement paths were sigmoid. The net velocity profile was usually bell-shaped with longer deceleration than acceleration, but for some slow movements the velocity profile had a plateau. When the net velocity profile was bell-shaped, the averaged sagittal movement paths and normalized x (protraction) and z (lifting) velocity profiles were virtually superimposable for fast and slow movements: thus, movement speed was changed by parallel scaling of protraction and lifting. Comparison of movement paths and velocity profiles amongst the different cats revealed considerable differences. The x profile was unimodal in one cat and double peaked in five cats: the second component was pronounced in two cats and small in the other three. The z profile was unimodal and, except for one cat, it had later onset and summit than the first component of the x profile. In contrast to the interindividual differences, there was a high degree of intraindividual constancy over 6-12 months. It is postulated that the interindividual variability depends on chance differences established early during learning of the task and that the imprinted pattern remains, resulting in intra-individual constancy.

Characteristics of target-reaching in cats. II. Reaching to targets at different locations.

Trajectory formation of unrestrained forelimb target-reaching was investigated in relation to the effect of a change in target location. Sagittal displacement of the target (6 cm in each direction) gave a selective change of velocity in the x direction (protraction) with an increase or decrease at larger and shorter distances, respectively. In the case of a double-peaked x velocity profile, the change was mainly with respect to the first major component. The shape of the y (sideways) and of the z (lifting) velocity profiles were both almost unchanged, but the onset of the movement in the z direction changed with the x distance. Vertical displacement (4 cm up or 5 cm down) gave increased velocity in the z direction (lifting) when the target was above the normal mid-position and decreased velocity when the target was lower. The velocity was changed with constant rate of rise, so that the rise time increased when the target was elevated and shortened when the target was lowered (pulse width control policy). The change in the z velocity was not selective. In cats with a double-peaked x velocity profile, the second component decreased when the target was elevated and increased when it was lowered. With excessive lowering of the target (14 cm down), the first x velocity component was very much reduced in amplitude so that protraction depended mainly on the second x velocity component. In the cat with a unimodal x velocity profile, a second component appeared in the x and net velocity profiles when the target was excessively lowered.(ABSTRACT TRUNCATED AT 250 WORDS)

Descending pathways mediating disynaptic excitation of dorsal neck motoneurones in the cat: facilitatory interactions.

Facilitatory interactions between disynaptic EPSPs evoked from the contralateral tectum, ipsilateral tegmentum and contra- and/or ipsilateral pyramid have been investigated in dorsal neck motoneurones of the cat. Monosynaptic convergence on common intercalated neurones was found from ipsi- and contralateral pyramidal, contralateral tectal and ipsilateral tegmental fibres. In addition, disynaptic facilitation was observed from ipsilateral pyramidal fibres on disynaptic contralateral pyramidal EPSPs. Transection of cortico-fugal fibres in the pyramid showed that the location of the interactions occurred in the lower brain stem, suggesting that reticulospinal neurones are mediating the effects.

Descending pathways mediating disynaptic excitation of dorsal neck motoneurones in the cat: brain stem relay.

The location of intercalated neurones mediating disynaptic excitation from tectum, tegmentum and pyramids to dorsal neck motoneurones has been investigated by: (a) recording field potentials in the lower brain stem evoked from the above systems, (b) systematic stimulation in the brain stem during intracellular recording from motoneurones innervating the splenius, biventer cervicis and complexus muscles, and (c) comparing the effects of lesions of the brain stem with kainic acid on the disynaptic EPSPs elicited from the above three systems. Electrical stimulation of the contralateral superior colliculus evoked monosynaptic field potentials which were largest in the caudal pontine reticular formation rostral to the abducens nucleus and in the rostral part of the medullary reticular formation caudal to the abducens nucleus. Likewise, stimulation of the ipsilateral tegmentum (the cuneiform and subcuneiform nucleus) evoked field potentials which were large in the caudal medulla and small in the pons. In contrast, stimulation of the contralateral tegmentum was ineffective in evoking field potentials. Stimulation of the pyramid 2-3 mm rostral to the obex elicited monosynaptic field potentials in the reticular formation of the lower brain stem that were only about 25% of those from the superior colliculus. In contrast to the field potentials from the superior colliculus, the pyramidal ones were large in the medulla and small in the pons. Lesions of the reticular formation in the lower brain stem by unilateral kainic acid injection caused disappearance of disynaptic EPSPs in motoneurones from the above three systems. These results strongly suggest that the intercalated neurones mediating pyramidal, tectal and tegmental EPSPs are reticulospinal neurones in the lower brain stem. Systematic stimulation in various locations of the lower brain stem showed that monosynaptic EPSPs were evoked from the regions of the reticular formation which received projection from the above three descending systems. The effective regions for evoking the EPSPs in splenius (SPL) were located somewhat more dorsally than for biventer cervicis and complexus (BCC) motoneurones. The descending axons of presumed reticulospinal neurones were stimulated with electrodes placed in medial, middle and lateral positions at the spinomedullary junction. Monosynaptic EPSPs in SPL and BCC motoneurones were evoked from the medial and middle electrodes but not from the lateral electrode.

Tectal and tegmental excitation in dorsal neck motoneurones of the cat.

1. Intracellular recordings were made from 116 splenius (SPL) and 103 biventer cervicis and complexus (BCC) alpha-motoneurones in nineteen cats anaesthetized with alpha-chloralose. 2. Electrical stimulation in the contralateral tectum evoked disynaptic excitatory postsynaptic potentials (EPSPs) in the motoneurones when a train of stimuli was applied in the ventral layers throughout the superior colliculus. In the rostral half of the superior colliculus, these EPSPs were due to stimulation of ascending collaterals of tectofugal neurones. EPSPs of a presumed trisynaptic linkage could only be evoked from the dorsal and intermediate tectal layers in the caudal half of the superior colliculus. It is concluded that the tectofugal neurones which evoked the disynaptic EPSPs are mainly located in the caudal half of the superior colliculus. 3. Disynaptic EPSPs were evoked in the motoneurones by a train of stimuli in the contralateral fields of Forel and Zona incerta, which were due to stimulation of ascending collaterals from the tectofugal neurones. 4. Spatial facilitation experiments revealed that tectal disynaptic EPSPs in the neck motoneurones were mediated via reticulospinal neurones with convergent input from cortico-reticular neurones. 5. A train of stimuli in the ipsilateral tectum evoked EPSPs with latencies compatible with a trisynaptic linkage, while disynaptic EPSPs at low threshold could be elicited from the underlying tegmentum. Similar disynaptic EPSPs could be evoked from the ipsilateral fields of Forel. It is suggested that some of the disynaptic tegmental EPSPs in SPL and BCC motoneurones can be mediated via a tegmento-reticulospinal pathway which originates in the cuneiform nucleus.

Trigeminal excitation of dorsal neck motoneurones in the cat.

Excitation of dorsal neck motoneurones evoked by electrical stimulation of primary trigeminal afferents in the Gasserian ganglion has been investigated with intracellular recording from alpha-motoneurones in the cat. Single stimulation in the Gasserian ganglion ipsi- and contralateral to the recording side evoked excitatory postsynaptic potentials (EPSPs) in motoneurones innervating the lateral head flexor muscle splenius (SPL) and the head elevator muscles biventer cervicis and complexus (BCC). The gasserian EPSPs were composed of early and late components which gave the EPSPs a hump-like shape. A short train of stimuli, consisting of two to three volleys, evoked temporal facilitation of both the early and late EPSP components. The latencies of the gasserian EPSPs ranged from 1.6 to 3.6 ms in SPL motoneurones and from 1.6 to 5.8 ms among BCC motoneurones. A rather similar latency distribution between 1.6 and 2.4 ms was found for ipsi- and contralateral EPSPs in SPL and BCC motoneurones, which is compatible with a minimal disynaptic linkage between primary trigeminal afferents and neck motoneurones. Systematic transections of the ipsi- and contralateral trigeminal tracts were performed in the brain stem between 3 and 12 mm rostral to the level of obex. The results demonstrate that both the ipsi- and contralateral disynaptic and late gasserian EPSPs can be mediated via trigeminospinal neurones which take their origin in the nucleus trigeminalis spinalis oralis. Transection of the midline showed that the contralateral trigeminospinal neurones cross in the brain stem. Systematic tracking in and around the ipsilateral trigeminal nuclei demonstrated that the axons of ipsilateral trigeminospinal neurones descend just medial to and/or in the medial part of the nucleus. Spinal cord lesions revealed a location of the axons of the ipsilateral trigeminospinal neurones in the lateral and ventral funiculi. Interaction between the ipsi- and contralateral gasserian EPSPs showed complete summation of the disynaptic EPSP component, while the late components were occluded by about 45%. These results show that the disynaptic EPSPs are mediated by separate trigeminospinal neurones from the ipsi- and contralateral side, while about half of the late EPSPs are mediated by common neurones which receive strong bilateral excitation from commissural neurones in the trigeminal nuclei. Spatial facilitation was found in the late gasserian EPSP but not in the disynaptic gasserian EPSP by conditioning stimulation of cortico- and tectofugal fibres. Disynaptic pyramidal and tectal EPSPs, which are mediated by reticulospinal neurones, were facilitated by a single stimulation in the gasserian ganglion at an optimal interval of 2 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of a low pyramidal transection following previous transection of the dorsal column in cats.

In order to test the working hypothesis that motor deficits after low pyramidotomy may be due to transection of the cortico-cuneate pathway, a low pyramidotomy was made 2-4 months after a C2 dorsal column (DC) transection and tested on forelimb target-reaching and food-taking. Since food-taking recovered faster than after pyramidotomy alone, it is inferred that the loss of food-taking after pyramidotomy without previous DC transection is due mainly to transection of the cortico-cuneate pathway which controls transmission from forelimb Ia afferents to the motor cortex. The dysmetria and dyscoordination of target-reaching, on the other hand, was similar whether or not the low pyramidotomy was made after a previous C2 DC transection. It is tentatively suggested that dysmetria and dyscoordination of target-reaching after pyramidotomy may be due to transection of the pathway from the motor cortex which controls spinocerebellar transmission by its effect on the lateral reticular nucleus.

The pathway from Ia forelimb afferents to the motor cortex: a new hypothesis.

Forelimb target-reaching and food-taking in cats depend on different interneuronal circuitry in the spinal cord. On the basis of previous findings regarding the effect of transection of the corticospinal tract in the spinal cord, of high dorsal column (DC) transection, of low pyramidotomy and of pyramidotomy after previous DC transection, it is proposed that the food-taking movement is temporally linked to target-reaching as follows: During target-reaching, the position of the paw is signalled by the pathway from forelimb proprioceptors (mainly Ia) to the motor cortex with a relay in the main cuneate nucleus. The command for food-taking is issued by the motor cortex only when the pathway from the forelimb signals that the paw approaches the target correctly, as may be determined by a comparison of the information from the forelimb with an efference copy of the motor program for target-reaching. The hypothesis is based on previous results regarding the organization of the pathway from the forelimb to area 3a and the motor cortex, and regarding the cortico-cuneate pathway with selective projection from area 3a and motor cortex to the basal caudal part of the cuneate nucleus, where the proprioceptive information from the forelimb is relayed. Results relevant to the present hypothesis regarding responses of precentral neurones during active and passive movements in awake animals are briefly discussed.