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[Age-related changes in characteristics of evoked responses in the CA1 area of hippocampal slices after forelimb deafferentation].

The effect of forelimb deafferentation (median nerve transection) on postnatal development of hippocampal synaptic transmission was studied. Paired-pulse paradigm was applied to determine the properties of short-term plasticity, such as paired-pulse facilitation (PPT) in hippocampal slices. Significant changes in the time course of the PPT development were observed after the forelimb deafferentation. It was shown that the earlier described decrease in a population spike amplitude can be related not only to modification of synaptic efficacy but to some destructive processes, i.e., elimination of synapses and neurons. It was followed by the period by intensive formation of new synapses. The data suggest that there is no acceleration or delay in hippocampal development after the forelimb deafferentation but new intrahippocampal networks are formed.

Action Potentials↗

Convergence of forelimb afferent actions on C7-Th1 propriospinal neurones bilaterally projecting to sacral segments of the cat spinal cord.

Propriospinal neurones located in the cervical enlargement and projecting bilaterally to sacral segments of the spinal cord were investigated electrophysiologically in eleven deeply anaesthetized cats. Excitatory or inhibitory postsynaptic potentials from forelimb afferents were recorded following stimulation of deep radial (DR), superficial radial (SR), median (Med) and ulnar (Uln) nerves. 26 cells were recorded from C7, 22 from C8 and 3 from Th1 segments. The majority of the cells were located in the Rexed's laminae VIII and the medial part of the lamina VII. In 10 cases no afferent input from the forelimb afferents was found. In the remaining neurones effects were evoked mostly from DR (88%) and Med (63%), less often from SR (46%) and Uln (46%). Inhibitory actions were more frequent than excitatory. The highest number of IPSPs was evoked from high threshold flexor reflex afferents (FRA)--all connections were polysynaptic. However, inhibitory actions were often evoked from group I or II muscle afferents (polysynaptic or disynaptic) and, less frequently, from cutaneous afferents (mostly polysynaptic). Di- or polysynaptic IPSPs often accompanied monosynaptic EPSPs from group I or II muscle afferents. Disynaptic or polysynaptic EPSPs from muscle and cutaneous afferents were also recorded in many neurones, while polysynaptic EPSPs from FRA were observed only exceptionally. Various patterns of convergence in individual neuronal subpopulations indicate that they integrate different types of the afferent input from various muscle and cutaneous receptors of the distal forelimb. They transmit this information to motor centers controlling hind limb muscles, forming a part of the system contributing to the process of coordination of movements of fore--and hind--limbs.

Afferent Pathways↗

[Rearrangement of efferent activity of a locomotor generator controlling forelimb movements during electric stimulation of descending systems].

Data on reorganization of the efferent activity parameters of the forelimb locomotor generators during electrical stimulation of the descending systems were obtained during experiments on immobilized decerebrate cats. It has been found that a generator controlling the forelimb locomotor movement is characterized by existence of such a stable state when total influence of different descending systems on this generator is extremely limited. A conclusion is made that the sense of the activity reorganization in the locomotor generator of a forelimb under the effect of signals from descending systems brings the motor program to such a dynamic relation with a supraspinal inflow which provides sufficiently limitation and balancing of the influences of corresponding descending systems on the interneuronal nets, determining time and phase characteristics of the activity of these generators.

Animals↗

Development of the segmental innervation of the chick forelimb.

A number of recent studies have shown that during embryonic development the initial innervation of a target structure may be made up, in part, by axons which do not form part of the mature innervation of that structure. In the present study we have examined the motor innervation of the major muscles of the chick forelimb at different stages of development using HRP-uptake-labelling of motoneurons, electrophysiological recording and measurement of muscle contraction. In the mature White Leghorn chick the major contribution to the motor innervation of the forelimb is from spinal segments 14, 15 and 16. Using the HRP-labelling technique we have shown that at stages 26-29 of development motoneurons in segments 12-17 have axon terminals in the presumptive biceps muscle. Between stages 30 and 35, however, the axon terminals arising from segments 12, 13, 16 and 17 are lost, leaving the mature innervation from segments 14 and 15. We have also observed the loss of innervation of the biceps muscle by segment 16 using electrophysiological recording of compound action potentials in the biceps nerve and by measurement of the local contraction of the biceps muscle in response to stimulation of the segmental nerves. Similar changes in the innervation of the triceps, extensor metacarpi radialis, flexor carpi ulnaris and flexor digitorum profundus muscles have also been observed. These results are discussed in relation to the hypothesis that (i) the motoneuron pools and muscles in the developing spinal cord and forelimb are matched, (ii) that some axons which arrive in a particular muscle during early development are unable to form a stable connexion and (iii) that the inability of an axon terminal to form a stable connexion in a muscle results in the death of the motoneuron. Intracellular recording from muscle cells at stage 35 shows that the synaptic site on each cell is innervated by about three separate axons. Over the next few stages, however, all but one of the innervating axons is lost. From our contraction studies it is clear that the removal of the excess axon terminals after stage 35 is not associated with the establishment of the mature segmental innervation pattern of the muscle.

Action Potentials↗

The effects of thalidomide and two analogues on the regenerating forelimb of the newt.

Oral administration (3 mg/day) of thalidomide during the dedifferentiation and early limb-bud stages of newt forelimb regeneration produced a variety of specific limb deformities. Proximal and preaxial skeletal elements were the most severely malformed, e.g. preaxial hemimelia, severe proximal deformities, and preaxial polydactyly. Likewise, oral, daily doses (3 mg) of the teratogenic analogue, EM12, on days 7 and 8 following bilateral amputation caused the same incidence and type of forelimb abnormalities as did thalidomide. Conversely, the non-teratogenic analogue, EM87, when orally administered (3 mg/day) on days 7 and 8 post-amputation resulted in a low rate of limb deformities, similar in type to those seen in control regenerates. The type of limb deformities observed in the regenerating newt forelimb following thalidomide treatment nearly mimic those seen in the human and monkey syndromes. Therefore, the newt represents a possible model for investigating some of the problems associated with thalidomide teratogenesis.

Amputation, Surgical↗

Effect of endotoxin on glucose uptake by the isolated forelimb of the dog.

Recent research has demonstrated that an increase in glucose utilization by skeletal muscle occurs in hemorrhagic shock. It is conceivable that the hypoglycemia of gram-negative septic shock is, in part, due to increased glucose utilization by peripheral tissues. The hypothesis tested in this study was that there is an increase in glucose uptake by the isolated innervated and/or denervated forelimb of the dog subjected to endotoxin shock. Results indicate that endotoxin does not affect a net increase of glucose uptake by the isolated forelimb. No increase in uptake occurred when blood glucose concentration was normal. However, when endotoxin hypotension induced a significant hyperglycemia or when arterial glucose concentration was elevated by glucose administration an apparent increase in forelimb glucose uptake occurred. It is concluded that endotoxin does not increase the uptake of glucose by skin and muscle except that it causes hyperglycemia secondary to increased sympathoadrenal discharge in the shock state. Thus, if the dog becomes sufficiently hyperglycemic, an apparent increase in glucose uptake occurs, probably because of accumulation of glucose in the interstititial space of skin and muscle.

Animals↗

Effects of radius--ulna removal on forelimb regeneration in Xenopus laevis froglets.

Regeneration of boneless amputated forearms of adult newts was found to progress at a rate and to a degree comparable to amputated control limbs in which stump bones were not removed. In contrast, regeneration of boneless amputated Xenopus froglet forearms was significantly delayed and did not occur until two to three weeks following amputation. This is in comparison with the initiation of distal cartilage formation observed one week postamputation in control forelimbs of Xenopus froglets. The regeneration of cartilage in boneless forearms of adult newts was found to occur distal to the amputation level. In contrast, distal as well as proximal (centripetal) regeneration of cartilage was observed in the amputated boneless forearms of Xenopus. In froglets and newts, unamputated forelimbs in which forearm bones were extirpated did not initiate cartilage regeneration. Our findings support the hypothesis that forelimb regeneration in Xenopus froglets is primarily a tissue response. In comparison, limb regeneration in the adult newt is predominantly an epimorphic response.

Animals↗

Inhibition of vestibular and neck reflexes in forelimb extensor muscles during the episodes of postural atonia induced by an anticholinesterase in decerebrate cat.

In precollicular decerebrate cats, the multiunit EMG activity of forelimb extensor muscles (e.g. the triceps brachii) was recorded during sinusoidal stimulation of labyrinth and neck receptors at the frequencies of 0.026-0.15 Hz, +/- 10 degrees and the resulting responses were tested during tonic activation of a cholinergic mechanism. In agreement with previous findings, the first harmonic component of the EMG responses to roll tilt of the animal leading to selective stimulation of labyrinth receptors was characterized by an increased activity during side-down tilt and a decreased activity during side-up tilt (labyrinth responses); on the other hand just the opposite changes were elicited for the same directions of neck rotation (neck responses). For the parameters of stimulation reported above, the responses were always related to position and not to velocity of displacement. Intravenous injection of an anticholinesterase (eserine sulphate, 0.10-0.15 mg/kg) which produced a state of postural atonia, associated with bursts of rapid eye movements (REM), similar to that occurring spontaneously in unrestrained cats during desynchronized sleep or REM sleep, also decreased the tonic activity of the triceps brachii and abolished the EMG responses of this muscle to sinusoidal stimulation of labyrinth and neck receptors. This suppression persisted throughout the episode of postural atonia associated with REM bursts. The abolition of the labyrinth and neck reflexes acting on forelimb muscles was not only dependent on the dose of anticholinesterase, but also on the state of the animal. In fact, somatosensory or acoustic stimuli applied during the REM episodes abolished the rhythmic oculomotor activity and determined the prompt recovery of both the decerebrate rigidity and the EMG responses of the triceps brachii to labyrinth and neck stimulation. The postural atonia as well as the tonic depression of the vestibular and neck reflexes acting on forelimb extensor muscles can in part at least be attributed to cholinergic activation of medullary reticulospinal neurons exerting a postsynaptic inhibitory influence on extensor motoneurons. However, since these inhibitory reticulospinal neurons collaborate with excitatory vestibulospinal neurons to the motoneuronal responses during stimulation of labyrinth and neck receptors, we cannot exclude that the suppression of the vestibular and neck reflexes may also depend on occlusion of the unit responses at reticular level.

Animals↗

[Descending long-loop reflexes in the human spinal cord I. Facilitation of the triceps surae H reflex following stimulation of forelimb afferences (author's transl)].

The H reflex in the triceps surae muscle was elicited by just supraliminal stimulation of the tibial nerve. It was conditioned by paired impulses to the brachial plexus or the forelimb nerves and in some cases to other sites of the body. With a conditioning test interval of 32-47 msec a facilitation occurred which reached its maximum at about 80 msec and lasted for about 400 msec. The facilitation evoked by ipsilateral conditioning had a shorter latency than that from contralateral (ipsilateral: 32-42 msec, contralateral; 37-47 msec). The facilitation at the optimum interval (about 80 msec) ranged between 1;5 and 11.3 times of the control values. Ipsilateral conditioning was slightly more effective than the contralateral one (Fig. 1, 2). Stimulation of different forelimb nerves at an interval of 80 msec showed only insignificant differences in the amount of facilitation but was more effective than skin stimulation in the most cases (Fig. 3). Varying the intensity of the conditioning stimulus showed that facilitation occurred with just perceptable stimuli but it became more pronounced as soon as pain threshold (2-3 time of perception threshold) was exceeded (Fig. 3). This suggests that facilitation was mainly due to activation of nociceptor afferents. From the onset of facilitation and the conduction velocities of the respective forelimb and hindlimb afferents (cf. 6) a central reflex lantency of about 43 msec was calculated. To get further insight into the central connections of the reflex loop the H reflex was conditioned by paravertebral stimulation at C5 and L1 level. Both stimuli caused a distinct facilitation. However, the latency of the onset was 10-15 msec shorter with lumbar stimulation than with cervical stimulation. This and the similar time course of facilitation seen in animal experiments (12) suggest that an early part of facilitation is mediated via a descending propriospinal pathway. The major part, however, is supposed to be mediated via supraspinal pathways and seems to be related to a startle response.

Animals↗

Loss of lever press-related firing of rat striatal forelimb neurons after repeated sessions in a lever pressing task.

Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from the floor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive days. All animals acquired the task, evidenced by gradual improvements across sessions and eventual asymptotic levels in tone discrimination, reaction time, and efficiency of the lever press. Forelimb neurons fired in relation to the lever press during early sessions of acquisition but not after repeated sessions on the task. This difference in firing could not be attributed to differences in forelimb movements during lever pressing or to sampling from different populations of neurons in early versus late sessions. In view of evidence that striatal damage impairs acquisition of motor skills, the change in firing suggests that the striatal activity present in early sessions may be necessary for the acquisition of, but not the automatic performance of, learned motor responses.

Acoustic Stimulation↗

Organization of ascending pathways to the forelimb area of the dorsal accessory olive in the cat.

The purpose of these experiments was to define the topography of cuneate and spinal projections to the forelimb representation in the rostral dorsal accessory olive (rDAO). We were interested in determining whether the spinal and cuneate inputs constitute a homogeneous afferent source, and whether there is evidence that they serve different functional roles. We were also interested in determining whether the somatotopy of rDAO is the result of a point-to-point projection from its afferent sources, or whether the projection suggests a reorganization of afferents at the olive. Single unit recording was used to identify specific regions of rDAO, and the topography of inputs to the identified regions was determined by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a tracer. The results from retrograde tracing were confirmed by using WGA-HRP as an anterograde tracer from input sources. The cuneate and spinal neurons providing input to rDAO constitute two distinct neural populations. One consists of cells in the caudal cuneate nucleus and lamina VI of the rostral two cervical segments, the other consists of cells in the rostral cuneate nucleus. The cells in the caudal cuneate nucleus and the rostral cervical segments are large, multipolar neurons that form a single column of rDAO input cells. The column of cells projects to the contralateral rDAO in a topographic fashion with rostral regions of the column projecting to rostral rDAO, which contains cells that respond to somatosensory stimulation of the contralateral shoulder, trunk, and proximal forelimb. Caudal regions of the column project to caudal rDAO, which contains cells that respond to stimulation of the distal forelimb. Despite this topography, there is a large degree of overlap in the terminations from neighboring regions of the input column, indicating that a major reorganization occurs at the rDAO. The projection from the rostral cuneate nucleus arises from small neurons that project bilaterally to rDAO, and the input from the rostral cuneate nucleus lacks a clear topography. We propose that input from the cell column is responsible for the somatosensory sensitivity of rDAO neurons, whereas input from rostral cuneate is most likely modulatory, probably inhibitory, in nature.

Animals↗

Forelimb anatomy of New World monkeys: myology and the interpretation of primitive anthropoid models.

The forelimbs of 12 genera of New World monkeys, two genera of Old World monkeys, and a gibbon were dissected. Of the 54 muscles examined, 19 exhibited significant intergeneric variation. We present arguments for which morphologies are primitive and which are derived within platyrrhines and within anthropoids. We conclude that the forelimbs of Cebus apella and Callicebus moloch represent good models of the ancestral anthropoid morphology. Thus among living anthropoids they are most appropriate for comparisons with early fossil anthropoids. They are also useful for determining whether myological anomalies of human aneuploids are atavistic. Wagner tree analyses were conducted to assess the value of these myological characters in phylogenetic studies of platyrrhines. In most respects the Wagner trees were consonant with phylogenies previously proposed, although some hypothesized trees are less parsimonious than others in explaining our data. There is an unexpected number of derived features shared by Aotus and the Atelines. There are marked dissimilarities in forelimb musculature between Aotus and Callicebus.

Alouatta↗

Growth of axons into developing muscles of the chick forelimb is preceded by cells that stain with Schwann cell antibodies.

A study has been made of the development of limb and muscle nerves in relation to the first appearance of Schwann cells in the flexor digitorum profundus (fdp) and flexor carpi ulnaris (fcu) muscles of the avian forelimb. Schwann cells were identified by immunofluorescent techniques with antibodies to the glycoprotein HNK-1. Myotubes and nerves were identified by using antibodies to myosin and to neurofilament, respectively. At stage 24/25 the brachialis longus inferior (Bli n) and superior (Bls n) nerve trunks within proximal regions of the forelimb were surrounded by Schwann cells. These cells extended in a column for a distance of approximately 100 microns beyond the growing ends of nerves. At stage 26 both interosseus nerve (in n) and the medial-ulnar nerve (m-u n) had formed from the Bli n; each of these branches was surrounded by Schwann cells, which again extended approximately 100 microns beyond the growing ends of the nerves. By stage 26/27 the fdp and fcu muscles were clearly delineated by groups of myotubes. No nerves were detected within these groups; however, Schwann cells were observed between the myotubes. At stage 27 axons had left the in n and m-u n and grown into the fdp and fcu muscles, respectively. These axons were surrounded by Schwann cells. The present observations show that Schwann cells are located ahead of the main limb and muscle nerves as they grow into the fdp and fcu muscles of the limb. It is possible that these Schwann cells play a role in guiding nerves to their correct muscles in the developing chick forelimb.

Animals↗

Ontogenesis of learning: V. Variation in associative and nonassociative control of an operant forelimb response in infant rats.

To study ontogenetic variation in the mechanisms that control operant responding, infant rats 4-16 days old were trained to lift a forelimb in order to receive an infusion of a sucrose-milk solution (reinforcer). Although the learning processes that contribute to this behavior were to some extent functional in pups 5-6 days old (Experiment V), there were major age-related constraints on the performance of this response. We were unable to observe selective responding with the reinforced forelimb until pups were 9 days old (Experiment I). This was in part because pups tested when 7, but not 9 days old, were highly activated (as measured by responding with both forelimbs) by both the reinforcer (Experiment II) and cues associated with the reinforcer during training (Experiment IV). Implications of these findings are discussed.

Age Factors↗

Effects of an augmented nerve supply on forelimb regeneration in the adult mud frog, Rana rugosa.

Forelimbs of the adult mud frog Rana rugosa, when amputated midway through the zeugopodium, regenerate heteromorphically. The resulting regenerative outgrowths were mostly rod shaped and consisted of a cartilaginous core, in which the base was ossified, and muscle elongated distally along the cartilage, the whole being covered by connective tissue and skin. The tip of the regenerating muscle reached a point distally about one third of the length of the regenerative outgrowths. When the innervation of forelimb stumps was augmented by surgical diversion of the ipsilateral sciatic nerve, the amputated limbs regenerated mostly as spatula-shaped outgrowths, which were longer than those of normally innervated forelimbs. Such hyperinnervated regenerates exhibited less ossification of cartilage, or sometimes none at all. However, the regeneration of muscle was more extensive. That is, it reached more than half way along the regenerative outgrowth. Furthermore, denervation resulted in the absence of regeneration in all cases examined. These results clearly indicate that limb regeneration in Rana rugosa is dependent upon the degree of innervation, not only for the early stages of regeneration, but also for the growth and differentiation of the regenerative outgrowth.

Animals↗

Expansion of the Central Hindpaw Representation Following Fetal Forelimb Removal in the Rat.

We provide evidence that prenatal removal of a rat forelimb results in both a disruption of the anatomical representation which would normally correspond to the forepaw and in an enlargement of the adjacent hindpaw representation in the brainstem and cortex. This enlargement, which in some cases is as much as 100%, only occurs following complete forelimb amputation on embryonic day 17 (E17) or earlier. This coincides with the age at which forepaw afferents first arrive in the brainstem, suggesting to us that the expansion is permitted in part because ingrowing hindpaw afferents are in the presence of cuneate cells which have never been previously innervated; in animals older than E17, the expansion is prohibited by either an intrinsic age-dependent change in the cuneate cells, or a change imposed upon them by forelimb afferents. The number of cells in dorsal root ganglia subserving the expanded hindpaw areas does not differ from normal suggesting that the expansion of hindpaw territory within the brainstem reflects an increased terminal arborization by a normal complement of primary hindpaw afferents. We interpret the cortical enlargement to be an upstream reflection of the brainstem events. In cortex, the enlargement seems to result from an invasion of the dysgranular cortex by thalamic afferents arising from the ventral posterior nucleus.

Journal Article↗

The thalamic relay and cortical projection of group I muscle afferents from the forelimb of the cat.

1. Stimulation of Group I muscle afferents in contralateral forelimb nerves evoked a response in nucleus ventralis posterolateralis (VPL) in the thalamus of the cat. This response was located in the rostral two-thirds of VPL in a narrow zone near the dorsomedial border of the nucleus.2. Group I afferents in nerves from more than one of the muscles in the contralateral forelimb often excited the same thalamic relay cell. In addition these cells were often discharged by skin afferents from the contralateral forelimb. They were not affected by electrical stimulation of the dorsal column-lemniscal or the spino-cervico-lemniscal paths from the contralateral hind limb.3. In experiments with peripheral conduction paths of similar length, the latency of the thalamic focal potential evoked by stimulation of Group I muscle afferents in the nerve to m. extensor carpi radialis was 3.8 S.E. +/- 0.1 msec, and that of the focal potential evoked by skin afferents (n. radialis superficialis) in the centromedial part of VPL was 4.3 +/- 0.1 msec.4. The majority of the thalamic neurones discharged by Group I muscle afferents responded with a latency shorter than 1 msec to electrical stimulation of the cerebral cortex in the region of the post-cruciate dimple. A considerable number of the thalamic Group I relay cells were also discharged with a similar short latency from another cortical focus located on either side of the anterior suprasylvian sulcus near the S II hind limb areas. These responses were considered to be antidromic in nature, and the findings were interpreted as indicating two separate cortical projection areas for the Group I path. The second projection area was assumed to be located in the cortical fold formed by the anterior suprasylvian sulcus.5. Cortical stimulation also excited the thalamic Group I relay cells trans-synaptically. Trans-synaptic excitation with short (1-2 msec) and longer (2-7 msec) latency was observed. The cortical focus near the S II area was particularly potent in evoking trans-synaptic excitation in the thalamic region where the Group I relays were located.

Animals↗

Arterial blood pressure control during hindlimb and forelimb contraction in the dog.

This study examined the differential reflex cardiovascular responses evoked by separate contractions of the right hindlimb and forelimb and established the mechanism of a regional reflex vasodilation associated with hindlimb skeletal muscle contraction. The two groups of skeletal muscle were contracted separately by electrical stimulation (2-48 Hz) of the peripheral motor nerves. The left nonexercising hindlimb was perfused at constant flow. All blood pressure-regulating mechanisms were intact. Arterial blood pressure (ABP), left nonexercising hindlimb perfusion pressure (HLPP), and heart rate (HR) were recorded. HR was increased by skeletal muscle contraction. This response was independent of muscle group and contraction frequency. Increases in both ABP and HLPP were produced by high-frequency contractions (greater than 16 Hz) of either the hindlimb or forelimb. Decreases were evoked only by hindlimb contractions (greater than 8 Hz). The nonexercising skeletal muscle vascular bed contributed to this systemic depressor response by vasodilating. The mechanism involved a contraction-induced withdrawal of sympathetic nerve activity to that vascular bed. Concomitant with this response was an increase in heart rate that was blocked with propranolol. Similar heart rate changes evoked by forelimb contractions also were blocked with propranolol. These data indicate that sympathetic outflow to resting skeletal muscle depends on the origin and magnitude of the afferent signal from the contracting skeletal muscle.

Animals↗