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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.

Animals↗

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.

Animals↗

Forelimb lameness in the adult patient.

Lameness of the forelimb may be one of the more frustrating problems in small animal orthopedics. It is likely that numerous causes of forelimb lameness are not yet defined or well understood. The common and some less common causes of forelimb lameness are discussed as well as their means of diagnosis. The application of new diagnostic tools including arthroscopy and ultrasound are also discussed.

Animals↗

Spinocerebellar Purkinje cells and rat forelimb postures: a direction-dependent activity.

On anesthetized adult rats, we examined the possibility that the discharges of spinocerebellar Purkinje cells (PCs) are modulated by passive limb positioning. The rat forelimb was passively placed in four different sagittal positions while the simple spike spontaneous activity of single PCs was recorded; recordings started 5 s after the reaching of the posture and the forelimb remained at each position for at least 30 s. Although the activity of the PCs did not reflect the forelimb position, it showed hysteresis that depended in a cosine fashion on the direction of the preceding movement. This implies that the directional sensitivity of spinocerebellar PCs is persistent, since the activity levels were almost constant throughout the recording time.

Action Potentials↗

Effects of 'navicular' shoeing on equine distal forelimb kinematics on different track surface.

Orthopaedic shoeing applied for disorders such as navicular disease is mostly evaluated on hard track surfaces, but very often horses are ridden only on soft tracks. To compare the effects of normal shoes, eggbar shoes, and shoes with heel wedges (5 degrees) on the kinematics of the distal forelimb on hard and soft track surfaces, eleven sound Dutch Warmblood horses were led across three different tracks (an asphalt, a fibre/sand mix (= Agterberg), and a pure sand track) with three different shoe types (a normal shoe, an eggbar shoe, and a shoe with heel wedges). The hoof rotation and the maximal extension of the fetlock joint at midstance period were recorded by an infrared-light based gait analysis system (ProReflex) at walk and at trot. Statistical analysis revealed significant effects of track and shoe type, and a shoe-track interaction (p<0.05). On soft track surfaces, the equilibrium of the distal forelimb dictated a 1.5-4 degrees forward rotation of the normal or eggbar shod foot, the most on a sand track. The wedge effect on hoof rotation, however, was always significantly greater, but similar to that on the hard track surface (5 degrees forward rotation). The maximal fetlock extension was less on a soft surface, in particular on the sand track (p<0.05). This decrease was most pronounced when the horses were shod with heel wedges and was least pronounced with normal shoes. In conclusion, in particular the sand track allows a forward rotation of the hoof and thus relief of pressure in the navicular area, and a decrease in maximal fetlock extension and thus unloading of the fetlock joint. The extra forward rotation of the hoof induced by heel wedges on hard tracks was almost the same on soft track surfaces. Eggbars and fibre/sand mix tracks have intermediate effects on unloading of the distal forelimb.

Animals↗

A comparative molecular analysis of developing mouse forelimbs and hindlimbs using serial analysis of gene expression (SAGE).

The analysis of differentially expressed genes is a powerful approach to elucidate the genetic mechanisms underlying the morphological and evolutionary diversity among serially homologous structures, both within the same organism (e.g., hand vs. foot) and between different species (e.g., hand vs. wing). In the developing embryo, limb-specific expression of Pitx1, Tbx4, and Tbx5 regulates the determination of limb identity. However, numerous lines of evidence, including the fact that these three genes encode transcription factors, indicate that additional genes are involved in the Pitx1-Tbx hierarchy. To examine the molecular distinctions coded for by these factors, and to identify novel genes involved in the determination of limb identity, we have used Serial Analysis of Gene Expression (SAGE) to generate comprehensive gene expression profiles from intact, developing mouse forelimbs and hindlimbs. To minimize the extraction of erroneous SAGE tags from low-quality sequence data, we used a new algorithm to extract tags from -analyzed sequence data and obtained 68,406 and 68,450 SAGE tags from forelimb and hindlimb SAGE libraries, respectively. We also developed an improved method for determining the identity of SAGE tags that increases the specificity of and provides additional information about the confidence of the tag-UniGene cluster match. The most differentially expressed gene between our SAGE libraries was Pitx1. The differential expression of Tbx4, Tbx5, and several limb-specific Hox genes was also detected; however, their abundances in the SAGE libraries were low. Because numerous other tags were differentially expressed at this low level, we performed a 'virtual' subtraction with 362,344 tags from six additional nonlimb SAGE libraries to further refine this set of candidate genes. This subtraction reduced the number of candidate genes by 74%, yet preserved the previously identified regulators of limb identity. This study presents the gene expression complexity of the developing limb and identifies candidate genes involved in the regulation of limb identity. We propose that our computational tools and the overall strategy used here are broadly applicable to other SAGE-based studies in a variety of organisms. [SAGE data are all available at GEO (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSM55 and GSM56, which correspond to the forelimb and hindlimb raw SAGE data.]

Animals↗

Sensing platform for acoustic startle responses from rat forelimbs and hindlimbs.

A sensing platform with two piezoelectric transducers was designed and fabricated to measure acoustic startle responses from forelimbs and hindlimbs in the rat. Testing with a vibrator showed that separate forces were measured from 5 to 25 Hz with mean sensitivities of 2.395 and 2.022 V/N and mean linearity errors of 3.23 and 2.98% FS for the forelimb and hindlimb sensors, respectively. Forelimb and hindlimb response waveforms of male Sprague-Dawley rats had shapes similar to the commonly recorded wholebody response but were smaller in amplitude.

Acoustic Stimulation↗

Central regulation of motor cortex neuronal responses to forelimb nerve inputs during precision walking in the cat.

1. The responses of neurones in forelimb motor cortex to impulse volleys evoked by single pulse electrical stimulation (at 1.5 or 2 times the threshold for most excitable nerve fibres) of the superficial radial (SR) and ulnar (UL) nerves of the contralateral forelimb were studied in awake cats both resting quietly and walking on a horizontal ladder. Nerve volley amplitude was monitored by recording the compound action potential elicited by the stimulus. 2. In the resting animal 34/82 (41%) cells yielded statistically significant responses to SR stimulation, and 20/72 (28%) responded to UL stimulation. Some responses were confined to or began with an increase in firing probability ('excitatory' responses) and others with a decrease in firing ('inhibitory' responses), typically including a brief interruption of the spike train (zero rate). Cells responding to both nerves usually yielded responses similar in type. Most (78%) response onset latencies were less than 30 ms. Responses involved the addition or subtraction of from 3.4 to 0.1 impulses stimulus-1 (most <1 impulse stimulus-1). The distribution of response sizes was continuous down to the smallest values, i.e. there was no 'gap' which would represent a clear separation into 'responsive' and 'unresponsive' categories. Responses were commonest in the lateral part of the pericruciate cortex, and commoner among pyramidal tract neurones (PTNs) than non-PTNs. 3. During ladder walking most cells generated a rhythmic step-related discharge; in assessing the size of responses to nerve stimulation (20 studied, from 13 cells) this activity was first subtracted. Response onset latencies (90% <30 ms) and durations showed little or no change. Although most cells were overall more active than during rest both 'excitatory' and 'inhibitory' responses in both PTNs and non-PTNs were often markedly reduced in large parts of the step cycle; over some (usually brief) parts responses approached or exceeded their size during rest, i.e. response size was step phase dependent. Such variations occurred without parallel change in the nerve compound action potential, nor were they correlated with the level of background firing at the time that the response was evoked. When responses to both nerves were studied in the same neurone they differed in their patterns of phase dependence. 4. The findings are interpreted as evidence for central mechanisms that, during 'skilled', cortically controlled walking, powerfully regulate the excitability of the somatic afferent paths from forelimb mechanoreceptors (including low threshold cutaneous receptors) to motor cortex. Retention (or enhancement) of responsiveness often occurred (especially for ulnar nerve) around footfall, perhaps reflecting a behavioural requirement for sensory input signalling the quality of the contact established with the restricted surface available for support.

Animals↗

Image fusion of computed tomographic and magnetic resonance images for the development of a three-dimensional musculoskeletal model of the equine forelimb.

Biomechanical models that compute the lengths and forces of muscle-tendon units are broadly applicable to the study of factors that promote injury and the planning and effects of orthopedic surgical procedures in equine athletes. A three-dimensional (3D) generic musculoskeletal model of the equine forelimb comprised of bony segment, muscle-tendon, and ligament information, was developed based on high-resolution computed tomographic (CT) and T1-weighted magnetic resonance (MR) images from an isolated forelimb of a Thoroughbred racehorse. Image fusion was achieved through coregistration of CT and MR images with an image analysis program (Analyze) by adjustment of the relative position and orientation of fiducial markers visible in both modalities until the mutual information between the images was maximized. 3D surfaces of the bones and origin/insertion sites, centroid paths and volumes of the muscle-tendon and ligamentous structures were obtained from the multimodal (CT/MR) images using semiautomated and manual segmentation combined with sagittal and transverse color-cryosection anatomic images obtained from three other cadaveric equine forelimbs. Once bony and soft-tissue structures were reconstructed in the same coordinate system, data were imported to a software package for interactive musculoskeletal modeling (SIMM). The combination of integrated CT and MR acquisitions and anatomical images provided an accurate and efficient means of generating a 3D model of the musculoskeletal structures of an average-sized equine adult horse.

Animals↗

Forelimb tendon loading during jump landings and the influence of fence height.

Lameness in athletic horses is often caused by forelimb tendon injuries, especially in the interosseus tendon (TI) and superficial digital flexor tendon (SDF), but also in the accessory ligament (AL) of the deep digital flexor tendon (DDF). In an attempt to explain the aetiology of these injuries, the present study investigated the loading of the tendons during landing after a jump. In jumping horses, the highest forces can be expected in the trailing limb during landing. Therefore, landing kinematics and ground reaction forces of the trailing forelimb were measured from 6 horses jumping single fences with low to medium heights of 0.80, 1.00 and 1.20 m. The tendon forces were calculated using inverse dynamics and an in vitro model of the lower forelimb. Calculated peak forces in the TI, SDF and DDF + AL during landing were 15.8, 13.9 and 11.7 kN respectively. The relative loading of the tendons (landing forces compared with failure forces determined in a separate study) increased from DDF to TI to SDF and was very high in SDF. This explains the low injury incidence of the DDF and the high injury incidence of the SDF. Fence height substantially influenced SDF forces, whereas it hardly influenced TI forces and did not influence AL strain. Reduction of fence height might therefore limit the risks for SDF injuries, but not for TI and AL injuries.

Animals↗

An analysis of the representation of the forelimb in the ventrobasal thalamic complex of the albino rat.

1. Glass micro-electrodes have been used to record from a total of 998 units situated in the ventrobasal thalamic complex in the deeply anaesthetized albino rat. 2. Of these units 889 responded to electrical stimulation of the contralateral forelimb and fifty-one to the contralateral hind limb. The remaining units consisted of those with receptive fields on the trunk, head and those which responded to stimulation of more than one limb. Only the latter group of units showed any spontaneous activity in the absence of intentional stimulation. 2. Of the units which responded to electrical stimulation of the contralateral forelimb the receptive fields, modality and latencies of response were accurately determined for 505 units. The mean latency to supramaximal stimulation at the wrist was 4.49 (+/- 0.04 S.E. of mean) msec; and to mechanical stimulation (for 146 of these units) at the centre of the receptive field 6.58 (+/- 0.12) msec. The modalities were distributed as follows: light pressure, 391; heavy pressure, 47; hair movement, 40; claw sensitive, 15 and joint movement, 12 units. 4. The forelimb representation within the ventrobasal thalamic complex was somatotopically organized, the over-all appearance being that of an incompletely closed fist, palmar surface uppermost, thumb media, with the wrist caudal and the digital tips rostral and dorsal. 5. The central projection was distorted, some parts showing expanded representation, notably the tips of digits II and III and the medial wrist pad. Other parts were contracted, e.g. the wrist, forearm and shoulder. 6. Units with receptive fields consisting of the whole of a walking pad had shorter mean latencies, to tactile stimulation, than those whose field was a single spot on a pad. 7. Units were found to show an abolute unresponsive time to the second of a pair of identical supramaximal electrical stimuli of up to 50 msec, and a relative unresponsive time which could last up to 500 msec. The absolute unresponsive and relative unresponsive times to the second of a pair of tactile stimuli was shorter being 30 and 150 msec respectively. 8. The effect of decortication was to increase the excitability of thalamic units to peripheral stimulation both in the initial and later discharges.

Action Potentials↗

Forelimb electromyographic responses to motor cortex stimulation during locomotion in the cat.

The forelimb motor cortex was stimulated via chronically implanted microelectrodes whilst electromyographic (e.m.g.) responses were recorded from muscles in the contralateral forelimb in cats walking steadily at 0.5 m/s. The stimuli were brief trains of 0.2 ms pulses (11 pulses at 330 Hz), intensity 5-20 microA and e.m.g.s were recorded from the following muscles: biceps brachii, brachialis, long and lateral heads of triceps brachii, latissimus dorsi, cleidobrachialis, extensor digitorum communis, palmaris longus and flexor and extensor carpi ulnaris. During locomotion, stimulation at 20 microA readily elicited brief, short-latency changes in the normal locomotor patterns of activity in all muscles studied. The changes included production of e.m.g. at times in the step cycle when the muscles are normally inactive and brief augmentations or diminution of the normal locomotor e.m.g.s. Individual electrodes usually influenced several muscles, and muscles acting antagonistically about the same joint were sometimes co-contracted. The first effect on locomotor flexor muscles (i.e. muscles active in relation to the swing phase of the step cycle) was almost always excitatory and such effects were often phase-dependent, usually occurring when the muscle was normally active or about to become active. Extensor muscles were excited from some cortical loci but inhibited from others (inhibitions were necessarily detectable only when the muscles exhibited locomotor-related e.m.g.s). Some micro-electrodes elicited excitation during swing (when the extensors are inactive) but elicited inhibition during stance. In several muscles the latencies of the excitatory e.m.g. changes could be as short as 6 ms measured from the first pulse in the stimulus train. In flexors, but not in extensors, latencies fluctuated according to the timing of the stimuli relative to the step cycle. Reduction in stimulus intensity reduced the amplitude of the e.m.g. changes, the number of muscles influenced and often increased the latency. However, both excitations and inhibitions were sometimes evident at 5 microA and thresholds for excitatory responses were, over-all, substantially lower than in the resting animal. Longer trains of stimuli were capable of resetting the step cycle. Response thresholds were greatly increased after pyramidectomy. These findings support the view that the natural bursts of impulses discharged by pyramidal tract neurones during steady locomotion are likely to contribute to regulating forelimb muscle activity on a step-by-step basis.

Action Potentials↗

Osteopenic effects of forelimb immobilisation in horses.

Methods for the non-invasive assessment of bone quality were used to monitor the osteopenia induced by immobilising a forelimb in a cast. These techniques included the measurement of ultrasound velocity, single photon absorptiometry and radiographic photodensitometry. Serial measurements were made before, during and after an eight week period of immobilisation of the left forelimb of four adult standardbreds in a light fibreglass cast which included the foot and extended above the carpus. The measurements continued for 12 weeks after the removal of the cast. The results indicated a trend to decreasing bone strength and mineral content in both forelimbs, with the decreases being greater in the limb with the cast. The values tended to recover slowly after the removal of the cast, then more quickly after the horses returned to the paddock four weeks later. The differences between the limb with the cast and the opposite limb were significant at only a few points of comparison.

Absorptiometry, Photon↗

Hypothalamic and brachial nerve effects on circulation of isolated canine forelimb,.

Canine forelimbs were vascularly isolated and perfused at either constant inflow or constant inflow pressure. A comparison of the effects of electrical stimulation of hypothalamic pressor areas and brachial nerves was made on several vascular parameters. During constant pressure perfusion, forelimb resistance increased and total forelimb volume decreased. Additionally active vascular volumes measured with 131I-labeled albumin and 51Cr-labeled red cells decreased significantly. Capillary diffusion capacity product calculated from extraction of 86RbCl also decreased significantly as did the capillary filtration coefficient (CFC). The only significant differences between hypothalamic and brachial nerve stimulation were noted in the larger decreases in active volumes and CFC during the latter stimulations.

Animals↗

Forelimb blood flow distribution during hypothalamic dilator response.

An attempt is made to determine whether hypothalamically induced forelimb vascular dilation in the dog affects primarily exchange beds or shunt circuits. Slug injections of [131I] albumin and 86RbCl were used to measure the active vascular volume of the forelimbs and permeability surface area product (PS), respectively. Changes in total vascular volume (TVV), filtration, and capillary filtration coefficient (CFD) were measured by plethysmography. During stimulation, forelimb blood flow increased 25% and TVV increased an average 1.5 ml. There was no plethysmographic evidence of outward capillary filtration. Active vascular volume decreased 11%. PS decreased 11%, and CFC decreased 20%. These results point to a redistribution of blood flow from exchange circuits to faster flow channels. During constant-inflow perfusion, there was evidence from CFC and PS measurements that the capillary surface area was increased while active vascular volume decreased. The results observed with hypothalamic stimulation are different from those obtained with pharmacologic dilators and denervation. It is suggested that the former method has a more selective effect in lowering resistance in the faster shuntlike vessels.

Animals↗

Adaptations to free-fall impact are different in the shafts and bone ends of rat forelimbs.

Impact exercise can have beneficial effects on the growing skeleton. To understand what changes it promotes in the shafts and ends of weight-bearing bones, we measured the effects of impact from repetitive free falls in growing rats. Fischer 344 female rats, 6.5 wk old, were assigned to one of three groups (n = 10 each). Controls were not dropped, whereas those subjected to impact were dropped from 30 or 60 cm. Rats in both free-fall groups were dropped 10 times per day for 8 wk. Leg bones were mechanically tested, and their cross-sectional area (CSA), cross-sectional moments of inertia, and volumetric bone mineral density (BMD) were measured by peripheral quantitative computed tomography. In the shafts of the forelimbs, but not the hindlimbs, free-fall impact resulted in greater ultimate breaking force, minimum and maximum second moments of area, and CSA but not BMD. In the bone ends of the forelimb and tibial bones, trabecular BMD increased but CSA did not. Landing from 30 and 60 cm produced peak impact forces of 12.0 and 16.7 times the standing forefoot weight for each front leg and of 4.5 and 7.7 times the standing hind foot weight for each hind foot. Overall, free-fall impact affected the forelimbs by increasing trabecular bone density in the bone ends and improving the strength at the shaft as a result of geometric improvements. These results indicate that adaptation to impact may occur by different mechanisms in bone end and shaft regions.

Adaptation, Physiological↗

Properties of primary motor cortex output to forelimb muscles in rhesus macaques.

Stimulus-triggered averaging (StTA) of electromyographic (EMG) activity from 24 simultaneously recorded forelimb muscles was used to investigate properties of primary motor cortex (M1) output in the macaque monkey. Two monkeys were trained to perform a reach-to-grasp task requiring multijoint coordination of the forelimb. EMG activity was recorded from 24 forelimb muscles including 5 shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles. Microstimulation (15 microA at 15 Hz) was delivered throughout the movement task. From 297 stimulation sites in M1, a total of 2,079 poststimulus effects (PStE) were obtained including 1,398 poststimulus facilitation (PStF) effects and 681 poststimulus suppression (PStS) effects. Of the PStF effects, 60% were in distal and 40% in proximal muscles; 43% were of extensors and 47% flexors. For PStS, the corresponding numbers were 55 and 45% and 36 and 55%, respectively. M1 output effects showed extensive cofacilitation of proximal and distal muscles (96 sites, 42%) including 47 sites that facilitated at least one shoulder, elbow, and distal muscle, 45 sites that facilitated an elbow muscle and a distal muscle, and 22 sites that facilitated at least one muscle at all joints. The muscle synergies represented by outputs from these sites may serve an important role in the production of coordinated, multijoint movements. M1 output effects showed many similarities with red nucleus output although red nucleus effects were generally weaker and showed a strong bias toward facilitation of extensor muscles and a greater tendency to facilitate synergies involving muscles at noncontiguous joints.

Animals↗

Changes in motor responses induced by cerebellar stimulation during classical forelimb flexion conditioning in cat.

1. The ability of somaesthetic sensory inputs to produce structural changes in the connectivities of the central nervous structures involved in motor activity was tested with an alpha type of classical conditioning in chronically prepared adult cats. Repetitive sensory stimulation was applied at constant intervals after the activation of the motor circuits originating in the neurons or efferent axons of the cerebellar nuclei. A conditional stimulation (CS) applied to interpositus neurons was consistently paired with an unconditional stimulation (UCS) applied to the dorsal skin of the forelimb extremity to induce associative sensorimotor conditioning. The sites at which the conditional and unconditional stimuli were applied set up a simplified sensorimotor circuit including pathways transmitting both these stimuli and others mediating the expression of the conditioned responses. 2. To test the changes resulting from the conditioning, electrodes were implanted into the various relay structures on the cerebellar efferent pathways (ventrolateral nucleus motor cortex). The forelimb motor responses elicited by stimulating these relay structures were recorded with a potentiometer placed at the elbow joint. The angular displacement (amplitude) and latency of the responses and the percentage response rates were systematically quantified throughout the conditioning procedure and at test sessions carried out after the daily conditioning routines. 3. It was observed that daily repetition of paired CS-UCS led to an increase in the response rates and amplitudes of the forelimb flexions, which already began to occur very slightly on the first 4 or 5 days in response to the alpha conditioning, whereas the CS when applied alone failed to produce any changes in this initial response. Likewise, after the acquisition phase, repeated presentation of either the CS alone or the CS preceded by the UCS led to the extinction of the conditioned response, thus indicating that the observed changes were of an associative nature and that they depended on interactions between the motor and sensory inputs occurring somewhere in the CNS. In fact, the effects of conditioning were not generalized, but involved only a circumscribed circuit originating in the cerebellar neurons stimulated by the CS, which were activated concomitantly with the sensory pathways. 4. The conditioned response amplitudes were enhanced by 2.5-3 times their initial value. This enhancement persisted at the end of acquisition or after several days of consolidation, even when the paired CS-UCS sessions were interrupted for a period of 15 days to 2 mo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗