Gamma Motor Research Articles

Ultrastructural cytochemical localization of carbonic anhydrase activity in rat peripheral sensory and motor nerves, dorsal root ganglia and dorsal column nuclei

Some of the myelinated axons in rat peripheral nerves possess marked axoplasmic carbonic anhydrase activity [Riley, Ellis and Bain (1982) J. Histochem. Cytochem. 30, 1275–1288 ; Riley and Lang (1984) J. Hand Surg. 9A, 112–120] . A mixture of reactive and nonreactive neurons was a general observation in cervical, thoracic and lumbar ganglia. Nonmyelinated axons in lumbar dorsal roots were nonreactive; this was consistent with the lack of carbonic anhydrase in small sensory neurons. The carbonic anhydrase cytochemical method marked the larger afferent or sensory neurons and distinguished them from the smaller sensory neurons which were devoid of carbonic anhydrase activity. Nonmyelinated axons in the lumbar ventral roots were also nonreactive. Examination of muscle spindle innervation revealed staining of the primary sensory and gamma motor endings. This was strongly suggestive that some of the reactive sensory neurons were primary afferents and a portion of the reactive ventral root axons were gamma motor. The reactive central processes of spinal neurons sent collaterals into the grey matter of the spinal cord, entered the dorsal funiculi, and terminated in synaptic glomeruli in the cuneate and gracilis nuclei. Oligodendroglial cells appeared to be the only intrinsic cellular elements of the brain stem and spinal cord that exhibited high carbonic anhydrase activity. Both oligodendroglial and Schwann cells exhibited intense carbonic anhydrase activity in thin pockets of cytoplasm internal to compact myelin. The subcellular distribution of reaction product within sensory neurons and oligodendroglial cells agreed with biochemical reports of cytosol and membrane-bound forms of carbonic anhydrase. A general staining of the cytoplasm was suggestive of soluble carbonic anhydrase fixed in situ by the glutaraldehyde. Clumps of reaction product on the cytoplasmic surface of the endoplasmic reticulum possibly represented membrane-bound enzyme. Most of the membrane-bound carbonic anhydrase was associated with the internal membranes rather than the axolemma or limiting plasma membrane of the axon. In contrast to biochemical reports, a small fraction of neuronal mitochondria exhibited staining in the intracristal spaces. We suggest that the association of carbonic anhydrase with endoplasmic reticulum and mitochondria implicates the enzyme in regulating intracellular calcium because both organelles are known to sequester calcium.

End-plate spikes in electromyography are fusimotor unit potentials.

Spontaneous negative-positive potentials (NPPs) in electromyography were often activated by movement of the needle electrode or by tetanic stimulation. Coactivation of NPPs was sometimes observed in voluntary effort. Circulatory arrest or hyperventilation had no consistent effect. These facts and the differences of firing of NPPs from usual ectopic firing patterns indicate that NPPs are not driven by ectopic activity of motor axons. Instead, the firing of NPPs is similar to activity of muscle spindle afferents during fusimotor drive. We believe that NPPs are action potentials of intrafusal muscle fibers driven by gamma motor neurons.

Reinnervation of the gastrocnemius muscle by the contralateral S1 nerve root

Functional regeneration after transposition of a ventral nerve root was established in the adult cat. Reconstruction of the ventral root, using microsurgical methods, directed the right S1 ventral nerve root to innervate the left gastrocnemius muscle. Stimulus-induced unit responses were recorded from the left gastrocnemius muscle 5 to 8 months after the root cross, demonstrating the reestablishment of neuromuscular connections. The innervation of the left gastrocnemius muscle by neurons in the right vantral horn of the spinal cord was verified by injecting horseradish peroxidase into the muscle. Horseradish peroxidase reaction product was located in alpha and gamma motor neurons in the right S1 segment of the spinal cord. Computer-assisted determination of the soma area of the labeled neurons was compared with a normal S1 innervation of the gastrocnemius muscle. Analysis of the percentage of cells of a given soma area demonstrated an overall decrease in soma area in the operated animals. Because ventral root reconstruction can result in innervation of a foreign muscle, studies such as this may encourage repair or reconstruction of nerve roots to gain some functional recovery after spinal cord or nerve root injuries.

Motoneuronal and motor axonal innervation in the rat hindlimb: a comparative study using horseradish peroxidase.

In order to validate the horseradish peroxidase (HRP) technique as a quantitative method for assessing neuronal pools, we compared counts of labeled motoneurons to numbers of corresponding motor axons. Rat spinal motoneurons were labeled by immersing in HRP either the L4 radicular nerve or the normal or deafferented nerve to the tibialis anterior muscle (TA). The technique slightly under-valued the L4 motoneuronal population estimated by counting ventral root motor fibres, while in deafferented TA, counts of labeled neurons closely reflected numbers of motor axons. Measurements of neuron and nerve fibre diameters revealed good correlations of alpha and gamma motor estimates at spinal cord and nerve levels. Values were considered representative because of the approximation obtained in HRP-estimates between control and deafferented animals, indicating no significant damage from the surgical deafferentation.

Quantitative analyses of neuronal development in the lateral motor column of mouse spinal cord. III. Generation and settling patterns of large and small neurons.

The generation and settling patterns of large and small lateral motor column (LMC) neurons were compared in the spinal cords of three inbred strains of mice by means of tritiated thymidine autoradiography. No significant strain differences were observed for the number of large LMC cells (presumptive alpha motor neurons) that were heavily labeled on each injection day, although there were significant strain variations for this measure with regard to small LMC neurons (presumed gamma motor neurons and interneurons). The generation of both large and small LMC neurons began at the same time, but peak production of large cells preceded that of the small neurons. There were no strain differences observed for this relationship between the large and small cells. These findings indicate that the LMC, from the time of its initial formation, contains cells destined to become large and small neurons. The positions of large and small neurons within the adult LMC relative to their times of origin (settling patterns) were analyzed statistically. A significant ventrodorsal sequence for early-to-late generated cells was observed for both large and small LMC neurons. No significant strain differences were found in the analysis of settling patterns. A ventrodorsal settling pattern also has been described for amphibia (Prestige, '73) and, in conjunction with the proximodistal sequence of limb development described by other investigators, the ventrodorsal sequence could play a key role in the development of motor neuronal somatotopic organization.

Nervous Control of Occlusion

Receptors that convey sensory information about occlusal relationships to the CNS are found in the teeth, periodontal ligaments, muscles of mastication, and the temporomandibular joints. This sensory information enters the CNS largely through the maxillary and mandibular divisions of the trigeminal nerve. Cell bodies of these afferent neurons are found in the trigeminal ganglion (exteroceptive) and mesencephalic nucleus (proprioceptive). Axons of exteroceptive neurons are segregated into those conveying general sensory modalities such as touch, which enter the main sensory nucleus, and those conveying pain and temperature, which descend in the spinal tract of V and enter the spinal nucleus of V. Axons of proprioceptive neurons terminate in the motor nucleus of the trigeminal nerve. Second order neurons of the main sensory and spinal nuclei of the trigeminal nerve project to the thalamus. Third order neurons from the thalamus project bilaterally to the frontal and parietal cortex. The muscles of mastication, responsible for mandibular movement, are innervated by alpha motor neurons from the motor nucleus of V. When these neurons are stimulated, the masticatory muscles contract. The motor nucleus receives fibers from the frontoparietal motor cortex, trigeminal sensory nuclei, cerebellum, contralateral reticular formation, hypothalamus, amygdaloid nucleus, caudate nucleus, tectum of the midbrain, and cranial nerve nuclei (especially VII, which controls the muscles of the mouth and cheek and XII, which controls the musculature of the tongue). Input from all of these areas controls the muscles of mastication through the alpha and gamma motor neurons. Occlusal forces are produced during mastication, swallowing, and other activities. Tooth contacts stimulate sensory neurons. This information is conveyed to the CNS and integrated, and the appropriate adjustment of the mandible is made. Many questions concerning how the nervous system controls occlusion remain unanswered. How do the nervous pathways for the control of occlusal forces differ for individuals with normal occlusion or malocclusion, or for edentulous individuals or those with dentures? If the receptors of the teeth or periodontal ligaments provide the primary sensory input for the muscles of mastication, then clearly the individual with dentures or the edentulous individual must utilize alternative pathways to provide the appropriate control. Why do some people with obvious malocclusion not experience pain and others with minor occlusal problems experience great discomfort in the temporomandibular joint? Perhaps it is genetic, or the pathways used by each of these individuals may differ. What is the effect of repositioning the teeth or the entire jaw on established neuronal pathways? Perhaps the pathways are modified, or they degenerate and other pathways are established.

Effect of diazepam on the gamma motor system indicated by the responses of the muscle spindle of the triceps surae muscle of the decerebrate cat to the muscle stretch.

The experiments were performed on 37 intercollicularly decerebrate cats. The triceps surae muscle was subjected to trapezoidal stretches of 10 mm/s or 2 mm/s over a length of 14 mm. The reflex arc was left partially or fully intact. The effect of diazepam given intravenously on the discharge frequencies of group Ia afferent fibres from muscle spindles in the belly of the triceps surae muscle was studied. Diazepam depressed both the dynamic and the static gamma motor responses. When gamma motor fibres were selectively blocked by procaine a parallel shift of the tension-extension curve was observed. From comparison of the effect of procaine and diazepam on the phasic and static responses of the muscle spindle it was concluded that directly after the injection of diazepam the gamma motor activity was completely abolished at a dose as low as 0.1 mg/kg whereas the alpha motor system was only partly depressed even at higher doses. Differences in the effect of diazepam on the dynamic and static gamma system respectively, could not be found.

Lumbar motoneurons of man II: the number and diameter distribution of large- and intermediate-diameter cytons in "motoneuron columns" of spinal cord of man.

Using a methodology which corrects for split cell error, and for the linear relationship between diameter of nucleolus and of cell body (cyton) and using semi-automatic methods of counting and sizing and programmed calculation and plotting, the number and diameter histograms of cytons of L-3, L-4, and L-5 motoneuron columns of 18 reference spinal cords of man (ages 17 to 82 years) have been evaluated. The number and frequency distribution of diameters (diameter histograms) of myelinated fibers of L-3, L-4 and L-5 ventral spinal roots (VSRs) had been determined in a preceding study as a control to validate the estimated number of alpha and gamma motoneuron cytons determined in this study from the same segment of spinal cord. The diameter histograms of cytons of motoneuron columns consistently contain three discrete peaks: a large-diameter peak (CL), an intermediate-diameter (CI) and small-diameter peak (CS). To illustrate, on the average, there were 4874 ± 585 large cytons and 1700 ± 564 ← intermediate cytons in the L5 segment of spinal cord. A reasonably close concordance was found between the average number of large cytons of spinal cord segments and the number of large-diameter myelinated fibers of ventral spinal roots (VSRs) (0.91, 0.94, and 0.98 for L3, L4 and L5 spinal cord segments and ventral spinal roots, respectively). For the ratio of the number of intermediate cytons to the number of intermediate axons the concordance was not as good (0.77, 0.85, and 1.14 for L3, L4 and L5 segments, respectively). Assuming that a cyton provides only one axon to VSR it is reasonable to infer from our studies that most large-diameter cytons are those of alpha motoneurons and that most of the intermediate-diameter cytons are those of gamma motor neurons. The greater number of axons than of cytons for the intermediate diameter group may be from a spurious inclusion of small-diameter axons (possibly pre-ganglionic autonomic fibers) with the intermediate-diameter group. On the average, the range of diameters of large-diameter cyton population in motoneuron columns was found to be 33 to 59 µm and for intermediate-diameter cytons was 24 to 33 µm. The total number of cytons per L3, L4 and L5 segments fell at a rate of ∽260, 175 and 200 per decade, respectively.

The effect of gallamine triethiodide on the activity of gamma motor neurons in the acute spinal cat.

Gallamine triethiodide, a drug commonly used in neurophysiological experiments, causes statistically significant and inconsistent changes in the information-carrying capacity of trains of action potentials generated by members of a population of gamma motor neurons recorded from the same cat under the same conditions during the same time period.

A possible hybrid mechanism for modification of visual direction associated with eye movements - the paralyzed-eye experiment reconsidered.

Previous work on the paralyzed-eye experiment concerning visual direction can be interpreted by a hybrid mechanism: outflow control of gamma motor fibers determines whether or not muscle spindles respond to changes in muscle length.

Differential blocking of motor fibers by direct current.

Differential blocking of alpha motor fibers was investigated in single fiber recordings when slowly rising direct current was applied to the gastrocnemius nerve in the cat. 18 out of the 26 (69.2%) L7 ventral root filaments, each of which contained 2-5 single alpha, or gamma motor fibers, or both, showed consecutive blocking from thicker to thinner fibers with increase of polarizing current. In the remaining 8 filaments (30.8%) thicker and thinner fibers were blocked almost simultaneously, or the order was reversed. The relation between the strength of the blocking current and conduction velocity is summarized on 30 alpha and 41 gamma fibers. The blocking current of each single fibers was shown to be inversely proportional to 2.01 power of conduction velocity (correlation coefficient -0.71). A regression line was also drawn for alpha fibers alone, its correlation coefficient being -0.60. Concerning prolongation of latencies of 82 single fibers (39 alpha and 43 gamma), it was shown that the conduction velocity, the smaller was the prolongation of latencies. In no experiments did the prolongation of latencies of single alpha fibers exceed the latency range of the mass alpha volley. Moreover, single alpha fibers were blocked earlier than or almost simultaneously with the mass alpha volley.

Modulation of dynamic parameters of muscle reflex by selective activation of its gamma system.

The ability of the gamma system to modify the dynamics of the muscle reflex control system is investigated. The dynamics of the triceps surae muscle in decerebrate cat preparations with intact reflex loops were modulated by contralateral tibial and peroneal nerve stimulation. The parameters of the mathematical models representing the muscle reflex system were estimated by the least squares method. The behaviour of the mathematical models of the system, under various degrees of gamma system stimulation, was then studied in response to disturbance inputs. It is shown that the gamma motor system is an efficient agent for carrying out modifications in the dynamics of the muscle reflex system. The possible functional significance of this phenomenon within the framework of operation of the muscular control system is discussed with reference to optimal adaptive system concepts.

The influence of the gamma motor system on jaw movements during speech: a theoretical framework and some preliminary observations.

A selective anesthesization technique was applied to the mandibular branch of the trigeminal nerve in man, and jaw activity was observed during speech under conditions of gamma motor blockade. The basic procedure involves special application of a conventional nerve block whereby it appears possible to selectively block the gamma efferent fibers of a motor nerve while leaving the alpha fibers unaffected. Measurement and analysis of jaw displacement, velocity, and acceleration under both normal and gamma block conditions revealed systematic effects for two experimental subjects. The experimental changes in jaw activity were interpreted to suggest that the spindle afferent facilitation of alpha motoneurons, thougnt to optimize the initiation of movement under normal conditions, was absent or disrupted. Thus, the jaw musculature was unable to produce adequate opening and closing forces with normal temporal control. Furthermore, from these data, under normal conditions, the spindle motor system would appear to operate most clearly under conditions of movement where large values of acceleration, velocity, and displacement were demanded. Finally, these findings were accepted as support for spindle motor system operation in oral-facial movements during the production of speech.

Depression by amantadine of tremor induced by reserpine and oxotremorine in the rat

Reserpine and oxotremorine tremor as well as the effect of amantadine on the tremor activity produced by both drugs were studied in rats with respect to changes in alpha and gamma motor activity.

Electrophysiology of pelvic and pudendal nerves in the cat

Reflex contraction of the detrusor muscle in decerebrated cats evokes depression of tonic activity in the external urethral and anal sphincter of the cat. This depression of activity may occur via synaptic inhibition of both alpha and gamma motor neuron pathways to these sphincters. The site of these effects is in the sacral spinal cord.

Histochemical and functional correlations in anterior horn neurons of the cat spinal cord.

The histochemical reaction for phosphorylase is completely lost from anterior horn neurons rich in phosphorylase within 72 hours after proximal or distal axonal section. Using this new type of axonal reaction as a marking technique in the anterior horn of the seventh lumbar spinal cord segment of the cat, we demonstrated that (i) alpha motor neurons of slow twitch motor units, like those of fast twitch motor units, are rich in phosphorylase and poor in succinate dehydrogenase, and (ii) interneurons and Renshaw neurons are rich in succinate dehydrogenase and poor in phosphorylase. Gamma motor neurons, because of their small size, are considered to be rich in succinate dehydrogenase and poor in phosphorylase. Thus, anterior horn neurons capable of higher firing frequencies (Renshaw neurons, interneurons, and gamma motor neurons) are richer in mitochondrial oxidative enzyme activity as marked by succinate dehydrogenase. Those firing at lower frequencies (both types of alpha motor neurons) are richer in phosphorylase activity and glycogen content and, thus, apparently better equipped for anaerobic glycolysis.

Histochemical differentiation of motor neurones and interneurones in the anterior horn of the cat spinal cord.

THE neurones of the anterior horn are a heterogeneous population of physiologically different cells. Alpha and gamma motor neurones, Renshaw cells and interneurones are recognized components1. Alpha motor neurones have been divided further into F and S types according to the fast and slow contractile properties of the muscle fibres that they innervate2. Anatomic investigations, largely by retrograde chromatolysis, have shown that the different neurones are intermingled, and that the larger are mainly alpha motor neurones while the smaller are a heterologous group of gamma motor neurones, Renshaw cells and interneurones3,4. Staining techniques selective for the Golgi body differentiate motor neurones from interneurones by the direction of their axons, but standard histological methods result in uniform staining without significant morphological distinction. We have used histochemical staining reactions to attempt neuronal differentiation in the anterior horn.

Response of gamma and alpha motor systems to phasic and tonic vestibular inputs

Responses in alpha and gamma lumbar motoneurons were recorded during quantifiable natural vestibular stimulation, in decerebrated cats, after destruction of the contralateral labyrinth. It was shown that the phasic responses of gamma motoneurons reach a maximum at approximately 0.5 sec after application of the stimulus, their intensity being dependent only on the angular velocity of head rotation. These features are predictable if it is assumed that this phasic response is due to activities originating in the ampullar receptors of the semicircular canals. The intensity of the tonic responses of both alpha and gamma motoneurons was found, on the contrary, to depend on the degree of angular rotation of the head, suggesting therefore their dependence upon macular receptor activity. The alpha and gamma motoneurons exhibited an independent behavior in response to natural vestibular stimulations, as revealed by the following evidence: (a) Responses were consistently present in the gamma but not in the alpha motor system. (b) There was no simple correlation between degree of gamma motor response and the changes in the alpha motor system. (c) Dorsal root section did not abolish alpha motor response to vestibular stimulation.

Motor activity following the silent period in human muscle.

1. When a muscle is unloaded during voluntary contraction, there is normally a silent period in the electromyogram. The silence is terminated by a sudden return of muscle action potentials.2. In order to investigate the mechanism of the terminal motor volley, the unloading reflex was studied in six human subjects. The independent variables were the initial muscular force, the inertia of the limb and the amount of motion permitted. The dependent variables were the size and latency of the terminal volley.3. During isometric contraction, the amplitude of the surface-recorded muscle action potentials increased monotonically with increasing muscular tension.4. The action potentials were significantly larger during the terminal volley than during the period before unloading.5. When acceleration of the limb was reduced by increasing the inertia, the terminal volley was decreased in size, but the latency was not affected.6. When movement was interrupted by a mechanical block, the latency of the terminal volley was reduced, but the size was not affected.7. The results suggest that the terminal motor volley is not the result of a decrease in Renshaw feed-back or in autogenetic inhibition.8. The motor volley must be regulated by proprioceptive feed-back, because it is affected by the velocity and displacement of the limb.9. The muscle frequently responded within 20 msec after motion of the limb was blocked. Hence it appears that the mechanism involves a spinal reflex.10. Because the motor discharge occurs while the muscle is shortening, it cannot be an ordinary stretch reflex. If the discharge is attributed to spindle afferent driving, one must assume that the gamma motor neurones are active during the silent period.11. The authors postulate a fusimotor reflex, which is driven by afferent impulses from the moving limb and excites the alpha motoneurones by way of the ;gamma loop'.

The effect of morphine on the discharge of muscle spindles with intact motor innervation

The action of morphine and pethidine upon the activity of the gamma motor system was studied by means of indicator spindles of the gastrocnemius and soleus muscle in spinalized, intercollicularly decerebrated or intact cats. Discharge frequency of the muscle spindles was determined before, during, and at the end of stretch of the muscles. In spinal animals, morphine (in doses up to 5.0 mg/kg) was ineffective; in decerebrate and intact animals it caused depression in about half of the cases. The gamma motor system proved to be more sensitive to morphine in intact cats than in decerebrate preparations: doses of 0.1 – 0.2 mg/kg reduced the impulse discharge in intact animals, while 1.0 – 2.0 mg/kg had to be given in decerebrate preparations to produce inhibition. The number of spindles responding to morphine was not markedly greater. Pentobarbital given previous to morphine did not enhance the sensitivity of the gamma motor system in the decerebrate preparation. Pethidine (3.0 and 5.0 mg/kg) had no effect upon gamma activity.