Reflex depression in rhythmically active monosynaptic reflex pathways

A study has been made of the depression that occurs when a monosynaptic reflex pathway is subjected to repetitive stimulation. Reflex depression has a dual origin. High frequency or early depression is postsynaptic in origin and results from subnormality in the motoneurons. Low frequency, late, or enduring depression is presynaptic in origin. The conditioning volley-test volley technique and the frequency-mean monosynaptic reflex amplitude relation yield similar information concerning reflex depression. Each method has its advantages and for some purposes one or the other of the methods necessarily must be employed. The results of a variety of experiments are consistent with the proposition that reflex depression in the monosynaptic reflex pathway originates by action in the group IA afferent fibers of muscle origin that are responsible for monosynaptic reflex transmission. Depression is present at a frequency of 0.1 per second (6 per minute) and absent at a frequency of 0.05 per second (3 per minute). Thus it is impractical for most purposes to employ repetition rates that satisfy the requirement for designation as "single shock" stimulations. The temporal course of enduring depression has been determined. It is identical with that for a number of other phenomena observable in monosynaptic reflex pathways, which suggests a common origin. The mechanism of low frequency or enduring depression is discussed in the light of this suggestion.     

Post-tetanic potentiation of response in monosynaptic reflex pathways of the spinal cord

Following tetanic afferent stimulation of a monosynaptic reflex pathway, the transmission through that pathway of isolated reflex volleys is enhanced for some minutes. Post-tetanic potentiation is comparable in the monosynaptic reflex arcs of flexor and extensor muscles. The facilitator and inhibitor actions of monosynaptic reflex afferent fibers, as well as the transmitter action, are potentiated following tetanization. Little post-tetanic change attends reflex transmission through plurisynaptic reflex arcs. Various tests for excitability change made independently of the tetanized afferent fibers reveal none or a slight depression. Hence the potentiating influence of a tetanus is limited to subsequent action on the part of the recently tetanized fibers themselves. Increase in the size of the individual impulses comprising an afferent volley such as might occur during positive after-potential, would accommodate the requirement for a limited process and provide for increased synaptic action. The proposed association between post-tetanic potentiation and positive after-potential (i.e. hyperpolarization) is supported by the following lines of evidence:- 1. Changes in intensity and duration of potentiation with change in frequency and duration of tetanic stimulation are characteristic of, and parallel to, the changes of positive after-potential in similar circumstances. 2. Afferent impulses are increased following a tetanus, and in a fashion that parallels the course of monosynaptic reflex potentiation. Post-tetanic potentiation, as here described, and after-discharge, whatever may be its mechanism, are unrelated phenomena.     

Posttetanic changes in the afferent and efferent activity of monosynaptic reflex in kittens

Both the afferent volleys from the dorsal root and the monosynaptic reflex discharges from the corresponding ventral root were recorded with hook electrodes during stimulation of the nerves innervating the triceps surae muscles. The effects of conditioning high frequency tetanus on the magnitudes of these afferents and reflex volleys were examined in kittens of postnatal age 1-90 days and in adult cats. In young kittens under barbiturate anaesthesia, large-amplitude monosynaptic reflex discharge can be evoked without prior conditioning. The amplitude of this reflex discharge decreased with increasing age of the animal. Application of conditioning tetanic stimuli to the muscle nerves resulted in posttetanic depression followed by posttetanic potentiation of the monosynaptic reflex. The magnitude of posttetanic depression was much higher than that of potentiation in the first postnatal week. As the age increased, the magnitude of depression decreased while the magnitude of potentiation increased. The afferent volley showed a considerable posttetanic potentiation in older kittens and cats. No significant potentiation or depression was observed in the younger animals. Possible mechanisms contributing to posttetanic depression and potentiation are discussed.     

Early post-tetanic potentiation and low frequency depression of some group I reflex actions

Group I reflex functions, namely monosynaptic reflex transmission, facilitation of synergists, and direct and disynaptic inhibition, show early post-tetanic potentiation following conditioning with a brief, high frequency, tetanus. Of these reflex functions, monosynaptic transmission always shows low frequency depression. Direct inhibitory pathways, and therefore inhibitory junctions, are insensitive to low frequency depression. The fact that direct inhibition can be potentiated shows it to be sufficiently labile that a decrease in efficacy at inhibitory junctions during repetitive activity should be revealed. Disynaptic inhibition often shows low frequency depression. As it is likely that inhibitory junctions in the direct and disynaptic pathways are similar, the low frequency depression of disynaptic inhibition is probably due to the properties of the excitatory relay between afferent fibers and interneurons in that pathway. Facilitation between synergists is often more depressed when the conditioning and testing volleys are nearly simultaneous than when they are separated by 1 to 1.5 msec. This result indicates that an early and rapid phase of action, responsible for homonymous and heteronymous transmission, is more sensitive to low frequency depression than is residual facilitation. In general, reflex transmission is more sensitive than are other aspects of action by group I fibers to events concurrent with and following repetitive activation.     

Mono-synaptic reflex responses of individual motoneurons

Individual motoneuron responses to a variety of afferent inputs have been examined. At a given input some motoneurons respond to every trial, some to no trial, and some respond to a certain percentage of trials that is characteristic for the motoneuron at that input. The performance of a motoneuron is expressed by means of a firing index that relates the number of responses to the number of trials. In a representative assemblage of individual motoneurons some 20 to 30 per cent display intermediate firing indices. This number, comprising an "intermediate zone" remains fairly constant at different levels of input although the individuals within it may be entirely different at two different levels of input. Frequency distribution of individuals with respect to firing indices is U-shaped. Intermediacy of firing indices depends upon temporal fluctuation of excitability which, in the first approximation, is normal. The individual motoneurons are approximately equally frequently distributed with respect to transmitter potentiality of their monosynaptic reflex afferent connections. The distribution of motoneurons with respect to transmitter potentiality of their monosynaptic reflex connections is considered representative of a natural pool in that the sum of their individual post-tetanic response behaviors accurately reproduces the course of post-tetanic potentiation in a natural pool.     

Inhibition of spinal reflex responses in the last period of embryogenesis

Some characteristics of spinal reflex reaction inhibition were studied in cat fetuses during the last three weeks of antenatal development. The experiments were conducted on fetuses with intact placental circulation. Restoration of the excitability of the spinal reflex arcs was very slow after stimulation of the dorsal root by a single stimulus. In embryos studied 20 days before birth the full inhibition of reflex responses lasted about 500 msec. Even 2–3 sec after a single stimulation of the afferent fibers the amplitude of the reflex response to the second stimulus was only 30–40% of the control value. It was determined that such long postactivation depression is unrelated to refractoriness or antidromic inhibition. The presence of a prolonged intense depolarization of afferent terminal fibers at these stages suggests a presynaptic inhibition as one of the most probable reasons for the prolonged postactivation depression. Another important factor in the appearance of postactivation depression is probably the morphologic and functional immaturity of synaptic structures. A reciprocal inhibition was observed in cat fetuses on the 10–12th antenatal day. On the basis of these data it is suggested that in embryogenesis presynaptic inhibition considerably precedes that of postsynaptic fibers.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 68–75, January–February, 1971.     

The effect of stimulation of Golgi tendon organs and spindle receptors from hindlimb extensor muscles on supraspinal descending inhibitory mechanisms

Experiments were performed in precollicular decerebrate cats to investigate whether proprioceptive volleys originating from Golgi tendon organs and muscle spindles may activate supraspinal descending inhibitory mechanisms. Conditioning stimulation of the distal stump of ventral root filaments of L7 or S1 leading to isometric contraction of the gastrocnemius-soleus (GS) muscle inhibited the monosynaptic reflex elicited by stimulation of the ipsilateral plantaris-flexor digitorum and hallucis longus (Pl-FDHL) nerve. The amount and the time course of this Golgi inhibition were greatly increased by direct cross-excitation of the intramuscular branches of the group Ia afferents due to ephaptic stimulation of the sensory fibers, which occurred when a large number of a fibers had been synchronously activated. The postsynaptic and the presynaptic nature of these inhibitory effects, as well as their segmental origin, have been discussed. In no instance, however, did the stimulation of Golgi tendon organs elicit any late inhibition of the test monosynaptic reflex, which could be attributed to a spino-bulbo-spinal (SBS) reflex. Conditioning stimulation of both primary and secondary endings of muscle spindles, induced by dynamic stretch of the lateral gastrocnemius-soleus (LGS) muscle, was unable to elicit any late inhibition of the medial gastrocnemius (MG) monosynaptic reflex. The only changes observed in this experimental condition were a facilitation of the test reflex during the dynamic stretch of the LGS, followed at the end of the stimulus by a prolonged depression. These effects however were due to segmental interactions, since they persisted after postbrachial section of the spinal cord. Intravenous injection of an anticholinesterase, at a dose which greatly potentiated the SBS reflex inhibition produced by conditioning stimulation of the dorsal root L6, did not alter the changes in time course of the test reflex induced either by muscle contraction or by dynamic muscle stretch. Conditioning stimulation of a muscle nerve activated the supraspinal descending mechanism responsible for the inhibitory phase of the SBS reflex only when the high threshold group III muscle afferents (innervating pressure-pain receptors) had been recruited by the electric stimulus. This finding contrasts with the great availability of the system to the low threshold cutaneous afferents. The proprioceptive afferent volleys originating from Golgi tendon organs as well as from both primary and secondary endings of muscle spindles, contrary to the cutaneous and the high threshold muscle afferent volleys, were apparently unable to elicit not only a SBS reflex inhibition, but also any delayed facilitation of monosynaptic extensor reflexes attributable to inhibition of the cerebellar Purkinje cells.     

Input-output relation in a flexor reflex

Observations have been made upon a typical flexor reflex with the aim of disclosing the changes in amount, latency, and temporal configuration of reflex discharge that take place as afferent input is varied from zero to maximal for the band of cutaneous myelinated afferent fibers that extends upward from approximately 6 µ in diameter (group II fibers). Reflex threshold is reached at 6 to 12 per cent maximal afferent input. From threshold to maximal input the relation between input and amount of output is essentially linear, latency on the average decreases, the shorter central paths in general gain preference, but the known minimum pathway, one of three neurons, does not transmit unless aided by convergent activity. Flexor reflex discharge may occur in several bursts suggesting the existence of closed chain connections in the internuncial pools of the spinal cord. At any given input there is, in successively elicited reflexes, little correlation between latency and amount of discharge, at first sight a surprising result for each variable can be taken as a measure of excitability status of the motoneuron population. However, latency of discharge indicates excitability at the beginning of the reflex event whereas amount of discharge is an expression of excitability over the entire period of discharge. Given a constantly and rapidly fluctuating excitability absence of correlation between these variables would be an anticipated result.     

Functional organization in the terminal segments of the spinal cord with a consideration of central excitatory and inhibitory latencies in monosynaptic reflex systems

Prominent monosynaptic and disynaptic reflex discharges characterize ipsilateral reflex transmission in the third sacral segment. Convergence upon the motoneurons from the two sides of the body is inhibitory, that through disynaptic paths excitatory. The relative latencies of excitation and inhibition of reflex responses, of excitatory and inhibitory synaptic potentials, and of various aspects of impulse discharge in motoneurons are considered. It is concluded: (1) that a direct (i.e. monosynaptic) action of primary afferent collaterals upon motoneurons is responsible for inhibition of monosynaptic reflex discharge of antagonist motoneurons within a myotatic unit; (2) that the inhibitory postsynaptic potential as described is not the primary agency for monosynaptic reflex inhibition of monosynaptic reflex discharge; (3) that, however, a common causal agent may be responsible for inhibition of reflex discharge and for generation of an inhibitory postsynaptic potential; and (4) that the inhibitory post-synaptic potential may be linked with, or be the agent for, inhibition of soma response.     

Convergence in Reflex Pathways from Multiple Cutaneous Nerves Innervating the Foot Depends upon the Number of Rhythmically Active Limbs during Locomotion

Neural output from the locomotor system for each arm and leg influences the spinal motoneuronal pools directly and indirectly through interneuronal (IN) reflex networks. While well documented in other species, less is known about the functions and features of convergence in common IN reflex system from cutaneous afferents innervating different foot regions during remote arm and leg movement in humans. The purpose of the present study was to use spatial facilitation to examine possible convergence in common reflex pathways during rhythmic locomotor limb movements. Cutaneous reflexes were evoked in ipsilateral tibialis anterior muscle by stimulating (in random order) the sural nerve (SUR), the distal tibial nerve (TIB), and combined simultaneous stimulation of both nerves (TIB&SUR). Reflexes were evoked while participants performed rhythmic stepping and arm swinging movement with both arms and the leg contralateral to stimulation (ARM&LEG), with just arm movement (ARM) and with just contralateral leg movement (LEG). Stimulation intensities were just below threshold for evoking early latency (<80 ms to peak) reflexes. For each stimulus condition, rectified EMG signals were averaged while participants held static contractions in the stationary (stimulated) leg. During ARM&LEG movement, amplitudes of cutaneous reflexes evoked by combined TIB&SUR stimulation were significantly larger than simple mathematical summation of the amplitudes evoked by SUR or TIB alone. Interestingly, this extra facilitation seen during combined nerve stimulation was significantly reduced when performing ARM or LEG compared to ARM&LEG. We conclude that locomotor rhythmic limb movement induces excitation of common IN reflex pathways from cutaneous afferents innervating different foot regions. Importantly, activity in this pathway is most facilitated during ARM&LEG movement. These results suggest that transmission in IN reflex pathways is weighted according to the number of limbs directly engaged in human locomotor activity and underscores the importance of arm swing to support neuronal excitability in leg muscles.     

Contour of auto- and cross-correlation histograms of the spike flows of monosynaptically connected neurons

By methods of neuronal interaction modelling--biomathematical (computer controlled experiment on molluscs neurones) and mathematical--in wide physiological ranges of parameters values, characterizing properties and conditions of neurones and synapses functioning, the forms were studied of auto- and cross-correlation histograms of impulse flows of neurones at forward and backward monosynaptic connections between them. Specific form is established of cross-correlation histogram of impulse flows of interconnected neurones in conditions typical of CNS of mammals, when the neurones are subjected to intensive random afferent synaptic bombardment and do not reveal any pace-maker properties. It is also shown that random afferent synaptic bombardment prevents the appearance of excitation reverberation in closed neuronal circuits.     

Monosynaptic reflexes of the cat spinal cord during the development of insulin hypoglycemia]

Insulin-induced hypoglycemia caused depression of rhythmic monosynaptic EPSP motoneurons of the lumbar cord in acute experiments on narcotized and spinal cats. It was demonstrated that growing depression of monosynaptic transmission was associated with the exhaustion of mediator operative fraction and not with any pre- or postsynaptic delay or inhibition over a period of initial hypoglycemia when the sugar content in the blood fell to the level of 50--60 mg%. The function disturbance of postsynaptic formations of monosynaptic reflex arc of spinal cord occured in more advanced hypoglycemia.     

Action of ammonium acetate on central primary afferent depolarization

Experiments on anesthetized spinal cats showed that ammonium acetate, injected intravenously (2–4 mmoles/kg) inhibits the depolarization of the central endings of primary afferent fibers activated by stimulation of afferent nerves. Inhibition of primary afferent depolarization is transient in character and develops parallel with depression of postsynaptic inhibition of monosynaptic reflexes. The depression produced by the action of ammonium was not due to blocking of negative postsynaptic potentials of the dorsal surface of the spinal cord or blocking of reflex electrical discharges in the ventral spinal roots. It is suggested that depression of primary afferent depolarization is due to a decrease in the emf for synaptic ion currents producing depolarization.Allergologic Research Laboratory, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 9, No. 1, pp. 52–60, January–February, 1977.     

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.     

Changes in the efficacy of transmission at synapses of the dorsal horn of the cat spinal cord observed during repetitive activation of cutaneous afferents

Inhibitory patterns in monosynaptic components of field potentials and potentials in the dorsal spinal cord surface were investigated during acute experiments on cats involving low-frequency stimulation of cutaneous peripheral nerves. Approximation of experimental data obtained from a theoretical plot was performed adopting a standard model of transmitter storage and release. Parameters of fractional release and replenishment of transmitter depleted from synaptic junctions were determined. Processes of replenishing supplies of transmitter for release were seen to intensify under rhythmic stimulation. A comparison between these experimental findings on the character of synapses of the monosynaptic reflex arc and others found in the literature indicated a similarity between the parameters of the mechanism underlying transmitter mobilization and release at different synaptic junctions formed by primary afferent fibers.Dnepropetrovsk State University Commemorating the 300th Aniversary of Ukraine-Russian Reunion, Dnepropetrovsk. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 491–497, July–August, 1987.     

Temporal fluctuation in excitability of spinal motoneurons and its influence on monosynaptic reflex response

Observations on temporal variation in monosynaptic reflex response in the acutely decapitate cat indicate the following: 1. Frequency distribution of response amplitude has a nearly normal form often with some degree of negative skewness. Response variation differs only moderately in form and magnitude from one preparation to another. 2. Temporal variation remains essentially constant at different levels of drive above that level required to complete the zone of variation. 3. The role of response variation in the determination of mean response amplitude is considered. 4. One of the major sources of excitability fluctuation in the "resting" cord is variation in background activity of interneurons.     

Phantom reflexes: muscle contractions at a frequency not physically present in the input stimuli

In the motor system, the periodic stimulation of one Ia-afferent input produces reflex muscle contractions at the input frequency. However, we observed that when two Ia monosynaptic reflex-afferent inputs are involved the periodic muscle contractions may occur at a frequency physically not present in the afferent inputs even when these inputs are sub-threshold. How can the muscles respond with such phantom reflex contractions at a frequency physically absent in the sub-threshold Ia-afferent input stimuli? Here we provide an explanation for this phenomenon in the cat spinal cord, that we termed “ghost motor response”. We recorded monosynaptic reflexes in the L7 ventral root, intracellular potentials in the motoneurons, and the associated muscular contractions elicited by stimulation of the lateral and medial gastrocnemius nerves. By stimulating with periodic pulses of sub-threshold intensities and distinct frequencies of 2 and 3 Hz the lateral and medial gastrocnemius nerves, respectively, we observed monosynaptic responses and phantom reflex muscle contractions occurring at the fundamental frequency (1 Hz), which was absent in the input stimuli. Thus we observed a reflex ghost motor response at a frequency not physically present in the inputs. We additionally studied the inharmonic case for sub-threshold stimuli and observed muscular contractions occurring at much lower frequencies, which were also conspicuously absent in the inputs. This is the first experimental evidence of a phantom reflex response in the nervous system. The observed behavior was modeled by numerical simulations of a pool of neurons subjected to two different input pulses.     

Monosynaptic reflex response of spinal motoneurons to graded afferent stimulation

Monosynaptic reflex response of spinal motoneurons to graded afferent volleys has been studied in natural populations and in a representative sample of individual motoneurons. By analysis of input-response relations certain of the requirements for initiation of reflex discharge have been defined. Initation of motoneuron discharge by monosynaptic afferent excitatory volleys results from the development of transmitter potentiality among members of a pool. Transmitter potentiality is considered to have the following characteristics: 1. It is a function of the number of active excitatory synaptic knobs, the degree to which such knobs are aggregated on the motoneuron soma, and the intensity of action per knob. 2. It has an appreciable spatial decrement and rapid temporal decay. 3. While transmitter potentiality has considerable dependence on number of active excitatory knobs, proximity of such knobs is an important variable. Total activation of a discrete zone does not appear to be necessary for initiation of discharge. In addition to initiation of discharge, volleys in monosynaptic afferent excitatory fibers facilitate response otherwise engendered. Such facilitation depends upon the production of an increment in transmitter potentiality. Facilitator potentiality has the following characteristics: 1. It depends principally on number of active excitatory synaptic knobs and intensity of action per knob. 2. Facilitatory action may result from synchronous activity in knobs interspersed among aggregations of knobs otherwise activated, thus fulfilling spatial requirements for transmitter potentiality. Alternatively a residual facilitation may result from a generalized action. 3. Residual facilitation has a slow temporal decay in comparison with transmitter potentiality.     

Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system

Animal experiments have shown that the nociceptive reflex can be used as an indicator of central temporal integration in the nociceptive system. The aim of the present study on humans was to investigate whether the nociceptive reflex, evoked by repetitive strong electrical sural nerve stimuli, increased when summation was reported by the volunteers. The reflexes were recorded from the biceps femoris and rectus femoris muscles in eight volunteers following a series of stimulations at 0.1, 1, 2, and 3 Hz. Each series consisted of five consecutive stimuli. Using 0.1- and 1-Hz stimulation, the reflex was not facilitated in the course of the five consecutive stimuli. Following 2- and 3-Hz stimulation, the reflex size (root mean square amplitude) increased significantly during the course of the fifth stimulus. This reflex facilitation was followed by a significant increase (summation) in the pain magnitude when compared with 1- and 0.1-Hz stimulation. Furthermore, the threshold for psychophysical summation could be determined. This threshold (stimulus intensity) decreased when the stimulus frequency (1–5 Hz) of the five consecutive stimuli was increased. The nociceptive reflex and the psychophysical summation threshold might be used to clarify and quantify aspects of temporal summation within the human nociceptive system.