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Recruitment of postmitotic neurons into the regenerating spinal cord of urodeles.

By using fluorescent tracers, we have investigated the origin of the cells that form the regenerating spinal cord after tail amputation in urodele amphibians. We show that spinal cord cells immediately adjacent to the amputation plane die and are removed by phagocytic cells. Spinal cells just anterior to these dying cells are destined to make the majority of the regenerating cord. The largest contribution is likely to come from the radial ependymal cells, but we also demonstrate that postmitotic neurons in this location can translocate into the regenerating cord. These neurons integrate into the regenerate structure and survive for at least 4 weeks. We find no evidence that these translocated neurons dedifferentiate and divide during this regeneration process. We discuss the possibility that these neurons survive long term in the regenerate cord and become part of the functional neuronal circuitry.

Ambystoma↗

Hippocampal activation during transitive inference in humans.

Studies in rodents have demonstrated that the integration and flexible expression of memories, necessary for transitive inference, depend on an intact hippocampus. To test this hypothesis in humans, we studied brain activation during the discrimination of a series of overlapping and non-overlapping arbitrary visual stimulus pairs. We report that transitive inference about overlapping pairs is associated with right anterior hippocampal activation, whereas recognition of non-overlapping stimulus pairs is associated with bilateral medial temporal lobe activation centered in the anterior parahippocampal gyrus. We conclude that immediate access to simple stimulus-stimulus relationships is mediated via the parahippocampal gyrus, whereas the flexible representation of memory requires the recruitment of the hippocampus.

Adult↗

Emergence and propagation of interictal spikes in the subcortically denervated hippocampus.

Spontaneous and evoked field potentials and cellular discharges of the subcortically denervated dorsal hippocampus were studied by multisite recordings in the freely behaving rat. Characteristic short-duration (< 100 ms), large-amplitude (up to 10 mV) transients, termed interictal spikes (IIS), were seen after fimbria-fornix (FF) lesion. Both pyramidal cells and putative interneurons fired maximally during IIS, with some interneurons sustaining long bursts (up to 400 ms) of high-frequency discharges (400-600 Hz) after the IIS. The speed of propagation of IIS along the longitudinal axis of the hippocampus varied from 0.2 m/s to > 3 m/s. The majority of IIS (type 1) could be accounted for by an enhanced activity of the intrahippocampal associational systems; a second class of IIS (type 2) had positive polarities in the stratum radiatum of CA1 and CA3 and propagated very rapidly (> 1.5 m/s). The authors propose that type 2 IIS reflect somatic depolarization and discharge of pyramidal neurons due to nonsynaptic (probably ephaptic) effects. Ephaptic interactions may also explain the longitudinal propagation of IIS at speeds higher than the conduction velocities (0.5 m/s) of hippocampal fiber systems. IIS emerged during the first 3 weeks after fimbria-fornix lesion, their incidence reaching a plateau of 2/min thereafter. During the same time period, paired-pulse suppression increased in the dentate gyrus. The amplitude of test responses to angular bundle stimulation was potentiated by small-amplitude IIS but suppressed by large-amplitude IIS. The incidence of IIS was significantly suppressed during walking relative to standing still. Tetanic stimulation of the angular bundle or handling-induced stress resulted in a 10- to 20-fold increase in the incidence of IIS that lasted for about 30 minutes. There was a negative correlation between evoked field PSP slope and population spike amplitude in the dentate gyrus of FF-lesioned rats; this correlation was positive in intact rats. The authors attribute the above pathophysiological changes to sprouting of both excitatory and inhibitory GABAergic pathways as a result of denervation of the intrahippocampal circuitry. They hypothesize that the majority of the observed physiological alterations can be traced to a weakening of feedforward inhibition coupled with an enhancement of feedback inhibition and excitation.

Animals↗

Neuritic growth from a new subline of PC12 pheochromocytoma cells: cyclic AMP mimics the action of nerve growth factor.

We have identified a new subline of PC12 pheochromocytoma cells (PC12D cells) in which neurites are extended within 24 hr in response to cAMP-enhancing reagents as well as in response to nerve growth factor (NGF), but not in response to epidermal growth factor or phorbol diester. Anti-NGF antiserum did not affect forskolin (FRK)-induced neuritic recruitment. FRK-induced neurites exhibited growth cones and contained secretion granules and many parallel arrays of microtubules as was the case with NGF-induced neurites. FRK, but not NGF, increased the levels of intracellular cAMP and activated adenylate cyclase in the membrane fraction. Both NGF and FRK enhanced the activities of tyrosine hydroxylase (TH), acetylcholinesterase (AchE), and ornithine decarboxylase (ODC), but not the levels of neuron-specific enolase. Enhanced levels of intracellular cAMP mimicked the effects of NGF on neuritic growth, TH, AchE, and ODC activities in PC12D cells, even though NGF does not act through elevation of levels of cAMP.

Adenylyl Cyclases↗

Strains and forces in selected carpal ligaments during in vitro flexion and deviation movements of the hand.

The forces induced in tiny wrist joint ligaments must be estimated in order to understand their role in the mechanism of the joint. We estimated forces in a number of selected ligaments in seven human wrist joint specimens, using a noninvasive method. The method is based on the rationale that the force generated in a ligament depends on its change of length with the joint under load. In vitro length changes of the ligaments were determined during flexion and deviation movements of the hand, using a roentgenstereophotogrammetric analysis technique. Subsequently, bone-ligament-bone (BLB) preparations were dissected from the specimens. From these BLB preparations the zero-force length and the force-elongation relationship were determined in a material testing machine. The forces generated in the ligaments during flexion and deviation were calculated by combining results on the in vitro ligament length changes, the zero-force length, and the force-elongation relationship. Large interspecimen variations of the force patterns were found. Due to this variability, it is not possible to obtain quantitative models for the kinetic behavior of the ligaments. However, qualitative trends could be distilled from the strain and force patterns. It is clear that for most ligaments, the zero-force lengths were not equal to the lengths they possessed in the neutral position of the hand. Furthermore, it could be shown which motions of the hand would most likely strain a particular ligament. It could be shown that the variations in the force patterns originate mainly from variations in the zero-force lengths, and from variations in the force-strain relationship between specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effects of selected drugs on an auditory or thalamic conditioned stimulus eliciting recruitment in the cat.

Minimally effective oral doses of chlorpromazine, imipramine, and pentobarbital necessary to block a discrete trial (bar-press) conditioned avoidance response were compared in cats chronically implanted with electrodes over the cerebral cortex and in the nucleus centralis medialis of the thalamus. Three conditioned stimulus contingencies consisting of tone and low or high voltage thalamic stimulation were presented. Minimal conditioned response blocking doses of these agents produced only slight qualitative changes in cortically recorded recruitment. Drug treatment affected the conditioned stimulus contingencies differentially, and the rank order in terms of ease of disruption of the conditioned avoidance response was high voltage thalamic conditioned stimulus greater than low voltage thalamic conditioned stimulus greater than auditory conditioned stimulus. The differential effect of these drugs might have been due to the additive inhibition of these agents and the thalamic conditioned stimulus on performance. With the exception of chlorpromazine, the behavioral effects of these drugs and their effects on recruitment were dissociated.

Acoustic Stimulation↗

Pure stimulus-sensitive truncal myoclonus of propriospinal origin.

The clinical and electrophysiological features of stimulus-sensitive truncal myoclonus are described in a 49-year-old woman. Touching the skin of the back and abdomen would evoke jerks in both ipsilateral and contralateral axial muscles; there was no spontaneous jerking. Multichannel EMG recordings showed bilateral short-latency muscle bursts at truncal recording sites both rostral and caudal to stimulus sites. The short latencies of muscle bursts in adjacent segments give evidence of a spinal origin of myoclonus; the pattern of recruitment and the velocity of spread suggest the involvement of propriospinal pathways. The presence of intrathecal IgG synthesis and of oligoclonal bands in the CSF point towards an inflammatory process which may underly the unusual type of myoclonus in this patient.

Abdominal Muscles↗

Muscle relaxation in Parkinson's disease: a reaction time study.

We tested the hypothesis that the relaxation reaction time in Parkinson's disease (PD) is delayed, as a sign of disorder in the control of voluntary motoneuron derecruitment. We compared, in the triceps brachii muscle, the reaction times (RTs) of the onset (O-RT) of electromyographic (EMG) activity during initiation of a contraction with the RTs of the termination of EMG tonic activity during full relaxation (R-RTs). Fourteen patients with idiopathic PD and 10 normal controls were examined. Mean R-RTs for all controls were 30 ms shorter than mean O-RTs. Mean R-RTs for all patients were approximately 70 ms longer than mean O-RTs. In two untreated patients levodopa therapy improved both O-RT and R-RT, but the difference between the two was unchanged. There was no correlation between EMG level and R-RT or between peak force and O-RT in either controls or patients. O-RT and R-RT were correlated with the bradykinesia score. In some patients, bursts of late activity were recorded after the R-RT; the duration of this activity was correlated with the duration and staging of the disease and with bradykinesia and rigidity scores. The reversed latency of onset and termination of muscle contraction in PD suggests an abnormality in the inhibitory spinal mechanisms, possibly stemming from a defect in the pathways descending to the spinal cord.

Aged↗

Mechanomyographic and electromyographic responses to eccentric muscle contractions.

Little is known regarding the modulation of torque during eccentric muscle actions. Mechanomyographic (MMG) and electromyographic (EMG) signals have been used to examine motor control strategies. The purpose of this study was to examine the MMG and EMG amplitude and frequency in relation to torque during eccentric muscle contractions. Eight women performed eccentric leg extension muscle contractions at 10-100% of peak torque (PT). A piezoelectric crystal contact sensor and bipolar surface electrodes were placed on the vastus medialis to detect the MMG and EMG signals. Polynomial regression analyses indicated that EMG amplitude (r(2)=0.994) and MMG wavelet center frequency (CF) (r(2)=0.846) increased linearly to 100% eccentric PT, whereas there were no significant relationships for EMG wavelet CF or MMG amplitude and eccentric torque. These results suggested that eccentric torque is primarily modulated through changes in motor unit firing rate.

Adult↗

Electrodiagnostic findings in acute porphyric neuropathy.

Of 115 patients with acute intermittent porphyria seen during a 20-year period, 11 had experienced an acute episode of quadriparesis. Nerve conduction studies performed on 8 of these 11 patients showed low-amplitude compound action potentials and normal velocity measurements. Needle electromyography demonstrated prominent fibrillation potentials, especially in proximal muscles. The changes in these findings with time confirm that this disorder is an acute axonal neuropathy.

Action Potentials↗

The effect of anticholinesterases on motor unit potentials in myasthenia gravis.

In most patients with myasthenia gravis, the mean duration and amplitude of motor unit potentials sampled in the extensor digitorum communis muscle, as well as the amplitude of the pattern of activity during full effort, increased after application of anticholinesterase. This appears to be a sensitive test for early detection of failure in neuromuscular transmission. In a series of 12 patients, the mean amplitude of motor unit potentials increased 30%-130% in 9, and the mean duration increased 10%-25% in 7. In 3 patients who failed to show an increase in amplitude in the extensor digitorum communis muscle, the amplitude of motor unit potentials increased in a facial or extraocular muscle after intravenous application of edrophonium. This increase in the amplitude or duration of motor unit potentials was even evident in 4 patients who failed to show a decrement in response of the opponens pollicis muscle to repetitive stimuli delivered to the median nerve at 3/sec and 5/sec. In 5 patients, responses evoked by stimuli delivered at 15/sec showed marked facilitation.

Acetylcholine↗

Effect of exercise on the motor unit.

The motoneuron part of this review deals with the changes in recruitment and firing rates of the motor unit types upon changes from a physically inactive life to endurance or strength training. The muscle fibers react to prolonged exercise by adaptation to a higher level of performance. A matter of discussion is the prerequisites for a transformation between the basic muscle fiber types, slow twitch and fast twitch, during voluntary (transsynaptic) activity, which is demonstrated after artificial nerve stimulation. The review includes current knowledge of muscle fiber transformation as an adaptive response to increased usage either by electrical stimulation or by transsynaptic neuronal activity. The metabolic adaptation related to increased endurance is reviewed with special reference to effects on muscle fibers. The increase in strength as a result of high resistance training is mainly the result of increased muscle cross-section. Whether this is solely the result of an increase in size of individual fibers or an increased fiber number is a controversial matter.

Action Potentials↗

Nonlinear force addition of newly recruited motor units in the cat hindlimb.

The present experiments were designed to examine the interaction of simultaneously active motor units. Pairs of medial gastrocnemius (MG) or soleus (Sol) units were stimulated individually and then together with constant frequency trains of 5-40 pulses per second. Stimulating two units asynchronously produced a smoother contraction than synchronous stimulation, but rarely a force increase. This contrasts with similar experiments on whole muscle bundles. A force increase may require that adjacent muscle fibers be active. The combined force of two motor units exceeded the algebraic sum of their separate forces by 12% in MG and 5% in Sol on average. The force a unit could sustain after a second unit fell silent was greater than the force the unit produced alone (21% in MG and 8% in Sol). We conclude that motor units produce more force when interacting than alone. During derecruitment the units remaining active produce more force than when recruited.

Animals↗

Antigravity posture for analysis of motor unit recruitment: the "45 degree test".

The maximum number of different motor unit action potentials (MUAPs), their firing rates, and total MUAP spikes/second recorded by monopolar needle electrode were determined for the biceps brachii muscle during 45-degree elbow flexion. There were 4.2 +/- 1.6 different MUAPs exceeding 100 microV. Mean firing rate was 10.0 +/- 1.7 Hz, and total MUAP spikes/second were 40.3 +/- 18. Recordings from 16 patients with neurogenic atrophy (NA) and just detectable weakness revealed corresponding values of 3.1 +/- 1.7 different MUAPs, a mean rate of 10.2 +/- 1.5 Hz and 30.6 +/- 19 total MUAP spikes/second, not different from normal. In these patients, increased force of muscle contraction was required to activate high threshold motor units firing at high rates. In each of 4 patients just able to hold the arm against gravity, 1 or 2 "overdriven" motor units firing at a mean rate greater than 20 Hz were recorded. In 8 patients with myopathy and just detectable weakness, greater than 100 total MUAP spikes/second were recorded. Antigravity posture as a reference level of innervation has the advantage that motor unit firing rate is set about that of physiologic tremor (10-13 Hz). Its application was helpful in quantifying recruitment.

Action Potentials↗

Quantitative electromyography in polymyositis: a reappraisal.

Manual analysis of motor unit action potentials (MUAPs) was performed in 33 patients with polymyositis of whom 16 were studied in the acute stage and 17 in the chronic stage. Contrary to common description of "myopathic potentials" as being of low amplitude, short duration, and polyphasic shape, the quantitated study revealed no difference as to amplitude of short duration MUAPs in patients and normal subjects though short-duration MUAP and short duration polyphasic potentials were 4 and 3 times, respectively, more common in patients than in controls. Although the mean duration of MUAPs usually was significantly shorter in polymyositis than in controls, the average scatter of MUAPs duration was the same in the 2 groups. The average incidence of polyphasic MUAPs was 4 times higher in patients than in controls, as was the incidence of those of long duration. To avoid misinterpretation of EMG findings due to an excess of polyphasic MUAPs, a greater number of individual potentials than usually recommended should be collected allowing a valid estimate of the mean duration of MUAPs of simple configuration.

Action Potentials↗

AAEM minimonograph #3: motor unit recruitment.

Motor unit recruitment is the process by which different motor units are activated to produce a given level and type of muscle contraction. At minimal levels of muscle contraction (innervation), muscle force is graded by changes in firing rate (rate coding) of individual motoneurons (MNs). At higher levels of innervation, recruitment is accomplished by the addition of different motor units firing at or above physiologic tremor rate. During slowly graded and ballistic increases in force, motor units are recruited in rank order of their size. In addition to MN soma diameter, other factors contribute to the selectivity of MN activation. For la afferent MN activation in the cat, synaptic density and efficacy as well as specific membrane resistance are also rank ordered for slow, fatigue resistant, and fast fatigue motor units with slow motor units recruited first. The central drive for motor unit activation is distributed to all the MNs of the pool serving a given muscle. Size-structure organization of the MN pool determines the order of recruitment and how MNs interact with each other. Disorders of the motor unit affect recruitment. A method for the clinical electromyographic assessment of recruitment is suggested. Assessment is made at three levels of innervation: minimal contraction for onset and recruitment firing rates; moderate contraction required to maintain the limb against gravity for the maximum number of motor units, their firing rates, and motor unit spikes/s; maximal voluntary contraction (MVC) for detection of high threshold enlarged motor units characteristic of reinnervation and completeness of the interference pattern (IP). Loss of muscle fibers results in early and excessive recruitment at minimal and moderate levels of innervation. Loss of motor units can result in both an increased rate and range of single motor unit firing at all levels of innervation. With reinnervation and enlargement of motor units, firing rates increase significantly and the interference pattern during MVC is incomplete.

Action Potentials↗

Turns-amplitude analysis of the electromyographic recruitment pattern disregarding force measurement. I. Method and reference values in healthy subjects.

We used turns-amplitude analysis to characterize the EMG recruitment pattern disregarding force measurement. The electrical muscle pattern of the brachial biceps (BB), abductor pollicis brevis (APB), medial vastus (MV), and anterior tibial (AT) muscles was analyzed during progressive increase in force from rest to maximum using the mean amplitude as an indicator of the force of the muscle. The following parameters were obtained on-line: the maximal ratio of turns to mean amplitude (peak-ratio, PR), the mean amplitude, and the number of time intervals (TI) between turns at PR and at near maximum force (NMF). The highest PR values were obtained in BB, the lowest in MV. Analysis of the distribution of the TI between turns at different degrees of voluntary contraction showed fewer spikes with short duration and small amplitude at high force compared with low force.

Adolescent↗

Motor unit recruitment pattern during low-level static and dynamic contractions.

Motor unit (MU) recruitment patterns were studied during dynamic and static contractions at workloads corresponding to 10% of maximal voluntary contraction force. The dynamic contraction consisted of a 20 degrees flexion and extension of the elbow performed with a velocity of 10 degrees/s. Motor unit potential trains were recorded from the brachial biceps muscle of 6 healthy females using a quadripolar needle electrode and a computerized decomposition program. Properties of the identified MUs were derived from concentric needle EMG. A total of 119 MUs were identified during dynamic contractions, 107 MUs during static anisotonic contractions, and 96 MUs during static isotonic contractions. The main result was that MUs recruited during different contractions showed similar properties and may belong to the same part of the motoneuron pool. This indicates that MU recruitment patterns during dynamic contractions may be almost as stereotypical as during static contractions and may even activate the same MUs.

Action Potentials↗