Intrafusal Research Articles

Distinctive patterns of static and dynamic gamma motor activity during locomotion in the decerebrate cat.

Simultaneous recordings were made from gamma (gamma) motor axons and from muscle spindle afferents of the medial gastrocnemius (MG) muscle during locomotion in decerebrate cats. The gamma-neurons were identified as static or dynamic (gammas or gammad) by correlating their behaviour during midbrain stimulation with changes in muscle spindle afferent responses to muscle stretch. On the basis of their behaviour during locomotion, gammas neurons could be divided into two groups. One group (type-1) showed strongly and smoothly modulated discharge increasing in parallel with the active muscle shortening in ankle extension, but with phase advance. The other group (type-2) also showed a modulated pattern, but with increased firing centred on the flexion phase. The proportions of the two were 13 type-1 and 7 type-2. The type-1 firing pattern accurately predicted the difference in firing frequency for secondary afferents obtained by subtracting from the recordings made during active movements the response of the same units to the movements repeated passively in the absence of fusimotor activity. The type-2 pattern also became consistent with the difference signal, when operated on by a phase lag appropriate to the effects of bag2 intrafusal fibres. These results suggest that there may be some degree of separate control of chain and bag2 intrafusal fibres. The discharge of gammad axons was also found to fluctuate with the locomotor cycle, with a pattern very distinct from that of the gammas records. The gammad firing frequency rose very suddenly from zero to a maximum at the onset of muscle shortening and continued into the beginning of lengthening. The term 'interrupted' discharge is suggested as a useful description. The timing of this discharge was shown to be appropriate for sensitising the primary afferents to detect the onset of stretch.

On electromyographic (EMG) gradients and movement-related brain activity: significance for motor control, cognitive functions, and certain psychopathologies

Electromyographic (EMG) voltage that rises continuously during motor performance or mental activity and falls precipitately at the end is known as an EMG gradient. Our review is based on 55 studies of EMG gradients, which were published during the period 1937–1994. The extremely wide diversity of situations yielding EMG gradients suggests the possibility that these gradients may be universal accompaniments of organized goal-directed behavioral sequences, overt and covert. Motor tasks and cognitive tasks (without any requirements for motor output) were found to have this in common: they both produced EMG gradients. EMG gradients were not observed during simple, repetitive exercises. On the efferent side, we propose a dual model for the production of EMG gradients, which is based on empirical findings. This model is discussed in relation to current views on central and peripheral neural control of muscle contractions, and on the electrical properties of extrafusal and intrafusal muscle fibers, with particular reference to surface electromyography. The complex relations between EMG gradient steepness and mental effort seemed well represented by the dual model, which was also useful in the interpretation of certain EMG gradients that were found in patients with anxiety disorders, tension-type headaches, and auditory hallucinations, respectively. On the afferent side, drawing on data from human and animal studies, we consider the evidence for movement-related brain activity generated by proprioceptive input, in relation to different types of feedback to the central nervous system during tasks that produce EMG gradients. On electromyographic (EMG) gradients and movement-related brain activity: significance for motor control, cognitive functions, and certain psychopathologies.

Effects of calcium on the discharge pattern of primary and secondary endings of isolated cat muscle spindles recorded under a ramp-and-hold stretch

The impulse activity of muscle spindles isolated from the cat tenuissimus muscle was investigated under varying concentrations of external calcium (Ca 2+). The outer capsule of the muscle spindle represents an effective diffusion barrier for Ca 2+ ions since activity changes were strong and rapid only if the capsule was partly removed from the sensory region of the receptor. The impulse activity of both primary and secondary muscle spindle endings was lowered by an increase in the external Ca 2+ concentration from 1.8 mM (normal Ringer’s solution) to 2.7 mM and raised by a decrease in the Ca 2+ concentration from 1.8 to 0.9 mM. Primary endings were generally more strongly affected than secondary endings. With primary endings the firing rate changed by 23–52% when the external Ca 2+ concentration was altered by 0.9 mM. With secondary endings the discharge frequency changed by 15–24%. The afferent discharge patterns were obtained under repetitive ramp-and-hold stretches and were analyzed with regard to influences of external Ca 2+ ions on the static and dynamic components of the endings’ responses. The stretch sensitivity and the adaptive response of both types of ending increased in the low Ca 2+ solution and decreased in the high Ca 2+ solution, but a specific effect on a single component of the responses to stretch was not observed. These findings indicate an overall change in excitability when the external Ca 2+ concentration was varied. The mechanical properties of the receptor were probably not affected since changes in the Ca 2+ concentration did not elicit a contraction or relaxation of the intrafusal muscle fibers. On the one hand, the observed effects can be explained according to the surface potential theory by an indirect influence of extracellular Ca 2+ ions on ion channels of the sensory nerve terminals, with Ca 2+ ions binding to negative charged sites at the endings’ outer membrane. On the other hand, the results are consistent with the supposition that Ca 2+ ions act directly on ion channels of the sensory membrane of muscle spindle endings.

Morphological variability and specializations in bovine extraocular muscle spindles

Bovine extraocular muscles were examined to determine whether the structure of their muscle spindles was notably different from those commonly encountered in mammalian limb muscles. Extraocular muscle spindles on the whole were shorter, and intrafusal fiber counts/spindle were more variable than in somatic muscles. No pronounced nuclear bags were seen in intrafusal fibers. Based on cross-sectional areas, intrafusal fibers in extraocular muscles could be loosely categorized as small or large types. Small fibers expressed more neonatal/fast myosin heavy chain and less embryonic myosin heavy chain than large fibers. When incubated for myosin ATPase, about 70% of the large fibers and 15% of the small fibers in spindles presented profiles that were characteristic of type I extrafusal fibers, and not of nuclear bag or nuclear chain fibers. The ratio of number of small intrafusal fibers to number of large intrafusal fibers in extraocular spindles was on average greater than the ratio of nuclear chain fibers to nuclear bag fibers that is typical for limb spindles of rodents and cats. Structural modifications at muscle spindle sensory regions, extrafusal-like fibers and intrafusal-like fibers with few equatorial nuclei and many myofibrils, may produce distinct afferent signals that are appropriate for sensorimotor integration in the specialized extraocular muscles.

Ultrastructure of Type 2A Extrafusal Muscle Fibers and Muscle Spindle Intrafusal Fibers of Adult Rats after Prolonged Swimming

We compared the ultrastructure of type 2A extrafusal muscle fibers, the nuclear chain, and other intrafusal fibers of muscle spindle (muscle stretch mechanoreceptor) in adult rats after prolonged swimming (5–10 h/day, 10 days). The Golgi apparatus was expressed moderately in type 2A extrafusal fibers and hypertrophied in the motor B zone of nuclear chain intrafusal fibers. Intense development of the Golgi apparatus in the nuclear chain intrafusal fiber appears to be related to glycogenolysis in the autophagous vacuoles, involvement in the lysosome activity, and plasma membrane renewal. “Recapitulation” of the mechanism of glycogen autophagy, which is observed in newborn rats during mobilization of glycogen from the liver and muscle, was demonstrated in adult rats under the influence of physical load in the nuclear chain and nuclear bag2 intrafusal fibers and in type 2A extrafusal fibers. This is accounted for by a weak differentiation of the intrafusal muscle fibers: structurally, they are similar to myotubes and have specific features of blood supply and innervation. Individual features of experimental adult rats may also play a certain role.

Effect of Intertrial Delay on Whole Nerve Cuff Recordings of Muscle Afferents in Rabbits

Objective. The effect of the stationary period on the muscle afferent responsiveness to passive stretch was studied to determine if muscle afferent activity might be suitable as feedback in motor-neural prostheses control. Methods. Muscle afferent activity was recorded using nerve cuff electrodes applied individually to the tibial and peroneal components of the sciatic nerve in five rabbit preparations. The ankle joint was rotated using a servomotor. The delay between trapezoidal movements was varied (excursion = 30°, velocity = 20°/s) and the duration was increased stepwise in successive trials(2 s, 5 s, 10 s, 20 s, 30 s, and 180 s). Results. An increase in amplitude of the afferent activity with increasing intertrial delay was observed. The afferent responses following a 2-s delay were subtracted from the responses following each of the remaining intervals (5 s-2 s, 10 s-2 s, 20 s-2 s, 30 s-2 s and 180 s-2 s) and were then compared. During the ramp phase a statistically significant difference was found in 85% and 76% of the cases for the tibial and peroneal nerve responses. Significant differences were below 21% for both nerves during four other phases examined. Conclusions. It is suggested that the enhancement in afferent responses caused by the increased intertrial delay may be explained by the change in the mechanical properties of the intrafusal and extrafusal muscle fibers. The consequences of this, when applying muscle afferent activity in motor-neuro prostheses, are discussed.

Proportions of slow myosin heavy chain-positive fibers in muscle spindles and adjoining extrafusal fascicles, and the positioning of spindles relative to these fascicles

Chicken leg muscles were examined to calculate the percentages of slow myosin heavy chain (MHC)-positive fibers in spindles and in adjacent extrafusal fascicles, and to clarify how the encapsulated portions of muscle spindles are positioned relative to these fascicles. Unlike mammals, in chicken leg muscles slow-twitch MHC and slow-tonic MHC are expressed in intrafusal fibers and in extrafusal fibers, suggesting a close developmental connection between the two fiber populations. In 8-week-old muscles the proportions of slow MHC-positive extrafusal fibers that ringed muscle spindles ranged from 0-100%. In contrast, proportions of slow MHC-positive intrafusal fibers in spindles ranged from 0-57%. Similar proportions in fiber type composition between intrafusal fibers and surrounding extrafusal fibers were apparent at embryonic days 15 and 16, demonstrating early divergence of extrafusal and intrafusal fibers. Muscle spindles were rarely located within single fascicles. Instead, they were commonly placed where several fascicles converged. The frequent extrafascicular location of spindles suggests migration of intrafusal myoblasts from developing clusters of extrafusal fibers toward the interstitium, perhaps along a neurotrophic gradient established by sensory axons that are advancing in the connective tissue matrix that separates adjoining fascicles.

The period of latency before a muscle receptor generates an action potential as a response to a muscle stretch

Six primary (Ia) and seven secondary (II) muscle spindle afferents and eight Golgi tendon organ afferents (Ib) from the tibial anterior muscle of the cat, recorded at the dorsal roots, were subjected to a sinusoidal stretch of the host muscle, the frequency of which increased linearly from 2 to 80 Hz over four different lengths of time. Both the amplitude of the sinusoidal stretch and the prestretch of the muscle were varied. The phase of the action potentials was determined. The phase of the action potential, driven 1:1, increased linearly with frequency. From the gradient of the phase of this action potential the muscle–muscle receptor latency was determined, i.e., the period of latency between the stretch of the muscle and the occurrence of the action potential at the muscle nerve where it enters the muscle. The muscle–muscle receptor latency had values lying between 3 and 8 ms: it was dependent on the experimental parameters and became shorter as the conduction velocity of the afferent fiber increased. In three experiments the muscle latency was determined, i.e., the period of latency before the stretch was transferred from the tendon of the muscle to the proximal third of the muscle belly. The muscle was stretched sinusoidally under the same varying parameters as given above. The length changes occurring in the proximal third of the muscle were measured with a piezo element. The muscle latency was determined from the slope of the phase of the zero points of the sinusoidal piezo length changes; the phase increases linearly with frequency. The muscle latency had values lying between 6 and 15 ms: it was dependent on the experimental parameters. The muscle spindle latency, i.e., the period of latency between the stretch of the polar parts of the intrafusal muscle fibers and the recording of the action potentials from the spindle nerve near the spindle capsule, was determined from 5 Ia fibers and 1 II fiber of isolated muscle spindles. The isolated muscle spindle was stretched under the same varying parameters as given above. The muscle spindle latency was determined from the slope of the phase of the phase-locked action potential. The muscle spindle latency as measured by our method proved to be 0 ms. The latencies of the three elements and their dependence on the experimental parameters are discussed in the light of the transfer properties of the muscle and the muscle receptors.

Observations on the number, distribution and morphological peculiarities of muscle spindles in the tensor tympani and stapedius muscle of man

Although the middle ear muscles have been described for the first time more than four hundred years ago their role in modulation and transmission of sound is not yet fully understood. Surprisingly very little is known about proprioceptors in these muscles, especially in man, although this seems to be the key to the understanding of their various functions. Therefore, the question for proprioceptive sensory organs in these muscles is still relevant. The tensor tympani and stapedius muscles of four women who had donated their bodies to our institute were taken. Complete serial sections of these muscles were made which were either impregnated with silver, stained with ferric oxide for acidic polysaccharides or incubated with antibodies against S-100 protein. Thereby four to eight (mean five) muscle spindles distributed along the whole muscle could be detected in the tensor tympani muscles. These spindles contain one to three intrafusal muscle fibres and their length ranges from 140 to 4270 μm (mean 1492.8 μm). Furthermore, in three stapedius muscles one to two (mean 1.7) muscle spindles were found. They were from 350 to 500 μm (mean 482 μm) long and contained only one intrafusal muscle fiber. Regarding the diameter of intrafusal muscle fibers in both, the tensor tympani as well as the stapedius muscle, no difference to extrafusal muscle fibers of these muscles could be detected. The structure of these spindles differs considerably from those found in skeletal muscles. The morphological findings presented strongly suggest that muscle spindles occur regularly in both middle ear muscles. The results presented herein are consistent with clinical findings obtained from electromyographic studies and may help to elucidate all functions the middle ear muscles might serve in man.

Testing the classification of static gamma axons using different patterns of random stimulation.

The possibility of using randomly generated stimulus intervals (with a Poisson distribution) to identify the type(s) of intrafusal fiber activated by the stimulation of single static gamma axons was tested in Peroneus tertius muscle spindles of anesthetized cats. Three patterns of random stimulation with different values of mean intervals [20 +/- 4. 47, 30 +/- 8.94, and 40 +/- 8.94 (SD) ms] were used. Single static gamma axons activating, in single spindles, either the bag2 fiber alone or the chain fibers alone or both types of intrafusal fiber were prepared. Responses of spindle primary endings elicited by the stimulation of gamma axons were recorded from Ia fibers in cut dorsal root filaments. Cross-correlograms between stimuli and spikes of the primary ending responses, autocorrelograms, interval histograms of responses, and stimulations were built. The characteristics of cross-correlograms were found to be related not only to the type of intrafusal muscle fibers activated but also to the parameters of the stimulation. Moreover some cross-correlograms with similar characteristics were produced by the activation of different intrafusal muscle fibers. It also was observed that, whatever the type of intrafusal muscle fiber activated, cross-correlograms could exhibit oscillations after an initial peak, provided the extent in frequency of the primary ending response was small; these oscillations arise in part from the autocorrelation of the primary ending responses. Therefore, cross-correlograms obtained during random stimulation of static gamma axons cannot be used for unequivocally identifying the type(s) of intrafusal muscle fiber these axons supply.

Evidence for fusimotor drive in stroke patients based on muscle spindle thixotropy

To study fusimotor function in stroke patients, we compared the amplitude of stretch reflexes elicited in flexor carpi radialis (FCR) after contraction of FCR with the wrist held flexed (`hold-short') or extended (`hold-long'). Seven subjects with impaired hand function and spasticity due to stroke, and seven healthy subjects were investigated. Surface electrodes recorded electromyographic activity of wrist flexors and extensors while subjects performed isometric wrist flexions with the wrist alternately in 15° of flexion or extension. After contractions the wrist was moved passively to the mid-position, and stretch reflexes were elicited via controlled mechanical taps delivered over the FCR tendon. For both groups, the amplitude of the stretch reflex was greater after `hold-short' than `hold-long' contractions. This finding is consistent with the `after-effects' of intrafusal fibre activation, and suggests that fusimotor neurones are activated during voluntary contractions of the paretic limb, just as in the limb of a healthy subject.

Extraocular muscle proprioceptors and proprioception.

Uncertainty of the roles of proprioception and efference copy in visual spatial perception persists. Proprioception has won back some support recently mainly on the evidence gained from physiological experiments in man, and rather than being mutually exclusive, the two mechanisms have been presented as collaborating. Another view supported by human and animal experiments states that current visual spatial perception may be served by efference copy whereas proprioception is responsible for temporal adaptations of the system. Certain characteristics of visuomotor cells of the monkey cortex can be explained assuming an efference copy input. Anatomical data from different sources are not easily reconciled. Disagreement about the nerve pathway of muscle afferents weakens arguments based on the results of open loop experiments involving nerve lesions in monkeys. The assumed presence of Golgi tendon organs in human extraocular muscles is no longer tenable and instead, palisade endings similar to those of cats and monkeys and other, irregular nerve endings are described. But man differs in having a limited and patchy distribution of neurotendonous endings and moreover, they may develop only after infancy. The allocation of a sensory function to palisade endings in myotendinous cylinders appears secure, at least in cats. Detailed examination of muscle spindles in man reveals anomalies of structure sufficient to question their capacity to provide useful proprioceptive information. One of the anomalies is the atrophy of intrafusal muscle fibres, present in both infant and adult muscles, and it is proposed that the redundant sensory endings, which do not appear to degenerate, search for new targets and may account for the random presence of tendon nerve endings. These observations place the role of proprioception in human extraocular muscles in jeopardy; they are unsupportive of the recent physiological studies and favour efference copy.

Vibration sensitivity of cat muscle spindles at short muscle lengths.

Experiments are described in which the vibration sensitivity was tested for primary and secondary endings of soleus muscle spindles of the anaesthetised cat. The vibratory stimulus was applied longitudinally to the muscle tendon and, after locating the site of the spindle in the muscle, applied transversely to muscle fibres directly overlying the spindle. All measurements were made with the muscle slack, at 20 mm shorter than its maximum physiological length (Lm-20 mm). Spindles were separated into two groups: spontaneous spindles, which maintained background activity at this length, and silent spindles, which did not. Two forms of muscle conditioning were used: hold-long, in which the muscle was stretched by 5 mm, contracted and then returned to the test length, and hold-test, in which a conditioning contraction was given at the test length. After hold-test, most spindles responded to longitudinal vibration; after hold-long, most did not. This difference in responsiveness was attributed to the presence or absence of slack in intrafusal and extrafusal fibres, due to the muscle's thixotropic property. When the vibration was applied transversely, at a site directly overlying the spindle, responses of silent spindles continued to show thixotropic behaviour, whereas responses of spontaneous spindles were almost independent of the form of muscle conditioning. It is proposed that the ability of spontaneous spindles to maintain background activity at short muscle lengths is due to connective tissue or elastic fibre links between the sensory ending and the spindle capsule. The vibratory stimulus, applied transversely, reaches the sensory ending via these strands which, as non-muscle tissue, do not alter their mechanical state as a result of muscle conditioning.

Chapter 10 Why are there Three Types of Intrafusal Muscle Fibers?

Publisher Summary This chapter describes a working scheme for the use of the three intrafusal fiber types. The bag 1 fibers provide control of the stretch sensitivity of primary afferents. Rapid changes in dynamic fusimotor output would be pointless because of the relative slowness of response of the bag 1 fibers and their inability to effectively oppose unloading. The bias levels of primary and secondary afferents could be set by bag 2 activity, but the slowness of bag 2 fiber contraction means that quick changes could not be made in this way. Gamma axons supplying bag 2 fibers alone can be expected, therefore, like dynamic axons, to fire tonically rather than phasically. Finally, the γ motoneurons that would be expected to show rapid modulation during movements should be those jointly supplying bag and chain fibers. The proposed function for the dynamic system is already well supported by spindle recordings in natural movements, but the crucial test for a dual function within the static system is to look for two distinct patterns of natural activity among γ s axons. The prediction is that one group, directed mainly to bag fibers, will fire tonically while the other, directed to chain or to bag 2 and chain fibers, will be modulated roughly in parallel with the active muscle contractions.

End plate spikes in the human electromyogram. Revision of the fusimotor theory

‘End plate spike’ (EPS) is a spontaneous action potential of a normal striated muscle. EPSs are found in local ‘active spots’ of the muscle. The prevailing hypothesis about the origin of EPSs states that when a needle electrode affects a motor nerve branch near the neuromuscular junction at the end plate zone, an increased leakage of acetylcholine to the synaptic cleft ensues. This elicits postsynaptic action potentials of the muscle fibre which can be recorded as EPSs with the same needle electrode. Thus EPSs are thought to be caused by needle injury or irritation of the motor axon. We suggest that EPSs are action potentials of intrafusal muscle fibres and that ‘active spots’ are in fact muscle spindles. Waveform analysis reveals three types of EPSs: small EPSs, not propagated outside the active spot either: i) with negative onset; or ii) with short positive initial deflection; and iii) large EPSs resembling propagated motor unit potentials (MUPs) but with a typical EPS firing pattern, distinctly different from that of the MUPs. Study of EPS activation in different manoeuvres associates small EPSs with intrafusal gamma motor units and large MUP-like EPSs with beta motor units.

Alpha-cardiac-like myosin heavy chain MHCI alpha is not upregulated in transforming rat muscle.

The expression of MHCI alpha, an alpha-cardiac-like myosin heavy chain isoform, was studied in extensor digitorum longus (EDL) and tibialis anterior (TA) rat muscles undergoing fast-to-slow transition by chronic low-frequency stimulation (CLFS), a condition inducing a transient upregulation of MHCI alpha in rabbit muscle. In order to enhance the transformation process, CLFS was applied to hypothyroid rats. mRNA analyses were performed by RT-PCR, and studies at the protein level by immunoblotting and immunohistochemistry, using the F88 antibody (F88 12F8,1) demonstrated in the accompanying paper to be specific for MHCI alpha. In total RNA preparations from slow- and fast-twitch muscles, MHCI alpha mRNA was present at minute levels, at least three orders of magnitude lower than in cardiac atrium. As verified immunohistochemically, MHCI alpha is present only in intrafusal fibres of rat muscle. Moreover, MHCI alpha is not expressed in extrafusal fibres and, contrary to the rabbit, was not upregulated at both the mRNA and protein levels by CLFS. These results support our notion of species-specific responses to CLFS. Another antibody reported to be specific to MHCI alpha, BA-G5, was also investigated by immunoblot and immunohistochemical analyses. Its specificity could not be validated for skeletal muscles of the rat. BG-A5 was shown to cross-react with MHCIIb and MHCI beta. These results question an upregulation of MHCI alpha in transforming rat muscles as reported in studies based on the use of this antibody.

Neurocalcin-immunopositive nerve terminals in the muscle spindle, Golgi tendon organ and motor endplate

The present study revealed the immunohistochemical distribution of neurocalcin, a three EF-hand calcium-binding protein, in the rat muscles and tendons. In the muscle spindles, annulospiral endings, which made spirals around the intrafusal muscles, showed intense neurocalcin-immunoreactivity. In the Golgi tendon organs, immunopositive thick nerve fibers entered the collagenous fibers resulting in the projection of many swelling terminals. In all examined muscles, nerve terminals in the motor endplates showed neurocalcin-immunoreactivity associated with the membranes of synaptic vesicles and mitochondria. These findings suggest that neurocalcin is distributed and regulates calcium signaling in both afferent and efferent nerve terminals in the muscles and tendons.

Correlated histological and physiological observations on a case of common sensory output and motor input of the bag1 fibre and a chain fibre in a cat tenuissimus spindle.

In muscle spindles of the cat, independent control of dynamic and static components of the response of the primary sensory ending to stretch is provided by separate motor inputs to the various kinds of intrafusal muscle fibre: dynamic axons (gamma or beta) to the bag1 fibres and static axons to the bag2 (typically gamma only) and chain (gamma or beta) fibres. Nonlinear summation of separately evoked effects during combined stimulation of dynamic and static motor axons appears to be due to mutual resetting by antidromic invasion of separate encoding sites, leading to partial occlusion of the momentarily lesser response by the greater. The encoding sites are thought to be located within the primary ending's preterminal branches which from first-order level are normally segregated to the bag1 fibre and to the bag2 and chain fibres. Here we describe the analysis of a special case that arose in a histophysiological study which had shown that the degree of occlusion was related to the minimum number of nodes between the putative encoding sites. Three-dimensional reconstruction of the primary ending revealed that the terminals of one chain fibre were derived entirely from the first-order branch that supplied the bag1 fibre, including one terminal that was shared directly with the bag1 (sensory cross-terminal). The other first-order branch supplied the bag2 and remaining chain fibres as normal. The degree of occlusion seen during simultaneous stimulation of a dynamic beta axon and a static gamma axon indicated that the encoding sites were separated by both first-order branches. Schematic reconstruction of the motor innervation revealed that the static gamma axon was most unlikely to have supplied the chain fibre which shared sensory terminals with the bag1, but that these fibres also shared a motor input with histological characteristics of beta type. Ramp-frequency stimulation of the dynamic beta axon at constant length evoked a driving effect which persisted after fatiguing the extrafusal component and was therefore explicable on the basis of the observed pattern of motor innervation, though the identity of the axon could not be conclusively proved. Individually, instances of shared sensory terminals and motor input of bag1 and chain fibres are rare in the cat; their combination in a single spindle with correlated physiology is described here for the first time. The observation is considered in relation to the importance of dynamic and static segregation in motor control, since it may imply that there is a lower limit to the degree of segregation that the developmental programme can provide.

Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3.

Muscle spindles are skeletal muscle sensory organs that provide axial and limb position information (proprioception) to the central nervous system. Spindles consist of encapsulated muscle fibers (intrafusal fibers) that are innervated by specialized motor and sensory axons. Although the molecular mechanisms involved in spindle ontogeny are poorly understood, the innervation of a subset of developing myotubes (type I) by peripheral sensory afferents (group Ia) is a critical event for inducing intrafusal fiber differentiation and subsequent spindle formation. The Egr family of zinc-finger transcription factors, whose members include Egr1 (NGFI-A), Egr2 (Krox-20), Egr3 and Egr4 (NGFI-C), are thought to regulate critical genetic programs involved in cellular growth and differentiation (refs 4-8, and W.G.T. et al., manuscript submitted). Mice deficient in Egr3 were generated by gene targeting and had gait ataxia, increased frequency of perinatal mortality, scoliosis, resting tremors and ptosis. Although extrafusal skeletal muscle fibers appeared normal, Egr3-deficient animals lacked muscle spindles, a finding that is consistent with their profound gait ataxia. Egr3 was highly expressed in developing muscle spindles, but not in Ia afferent neurons or their terminals during developmental periods that coincided with the induction of spindle morphogenesis by sensory afferent axons. These results indicate that type I myotubes are dependent upon Egr3-mediated transcription for proper spindle development.

Physiological signs of the activation of bag2 and chain intrafusal muscle fibers of gastrocnemius muscle spindles in the cat.

A method is described for identifying the effect of single gamma static (gamma(s)) axons on bag2 or chain intrafusal fibers using random (Poisson-distributed) stimuli. The cross-correlogram of the stimuli with the firing of spindle primary afferents took one of three forms. A large, simple, brief response was taken to indicate pure chain fiber activation and a small, prolonged response to indicate pure bag2 activation. A compound response with brief and prolonged components was taken to be a sign of mixed innervation. The correlogram components could be well fitted with lognormal curves. They could also be transformed into curves of gain as a function of frequency, which were convenient for estimating the strength of the effects. In 68 effects of gammas axons on Ia afferents, 16 were pure chain, 17 pure bag2, and 35 mixed. This distribution was significantly different (P < 0. 05) from that expected from chance nonspecific innervation of chain and bag2 fibers. Making use of the estimates of the strength of chain and bag2 effects derived from the gain curves, the classification was modified by treating mixed responses that had one effect more than five times stronger than the other as belonging to the dominant type. The distribution was then as follows: chain 16, bag2 28, and mixed 24. This differed very significantly from the prediction of chance distribution (P < 0.001). This evidence for some degree of specific innervation of chain and bag2 fibers is discussed in relation to previous work and with regard to the ways in which the two fiber types might be used in natural movements.