Effects of peripheral inputs from hindlimb on the monosynaptic reflex of motoneurons innervating tail muscles.

The effects of group II muscle (PBSt, GS) and cutaneous afferent (Sur, SPc, Tib) inputs from the hindlimb on the monosynaptic reflexes of motoneurons innervating tail muscles were studied in lower spinalized cats. Stimulation of the cutaneous nerves at the conditioning-test stimulus interval of about 10-20 ms facilitated and inhibited the monosynaptic reflexes of ipsilateral and contralateral tail muscles, respectively. The effects of the muscle nerve stimulation were not so prominent as those elicited by cutaneous nerve stimulation. The monosynaptic reflex was also inhibited by muscle nerve stimulation at 10-50 ms intervals. The effects of conditioning stimulation of the hindlimb peripheral nerves at short intervals were depressed or blocked by section of the ipsilateral lateral funiculus at S1 spinal segment. These findings show that the neuronal pathway from hindlimb afferents to tail muscle motoneurons passed the lateral funiculus of the spinal cord and modulates the motoneuronal activity of tail muscles.     

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.     

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.     

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.     

Post-tetanic potentiation of polysynaptic reflexes of the spinal cord

The phenomenon of post-tetanic potentiation has been studied in the cat spinal cord with particular reference to polysynaptic responses. Following tetanization of dorsal roots, these reflexes show an increased response, as measured in terms of their voltage-time area, with a predominant change in the earlier reflex pathways. Both of these changes in the reflex discharge have a time course of 15 to 25 seconds. Post-tetanic potentiation is also observed in response to stimulation of a dorsal rootlet following tetanization of another rootlet in the same or in a neighboring segment. This effect can be explained by post-tetanic changes in the terminals of secondary, and possibly higher order, internuncial cells, essentially similar to those changes in the primary afferent terminals which give rise to potentiation of the monosynaptic reflex.     

A comparison of experimental procedures of investigation of the dorsal root evoked ventral root reflex in the frog

Effects of the drug methyl-m-aminobenzoate (MS-222 Sandoz) on the dorsal root evoked ventral root responses were studied by electrophysiological methods in the frog spinal cord. A fairly quick and marked depression of the response was observed from which complete recovery was seen within 60 minutes. Larger doses or repeated injection of small amounts of the drug prolonged the recovery and the monosynaptic discharge component of the ventral root reflex often deteriorated irreversibly. - In further experiments, monosynaptic ventral root discharges were demonstrated in spinal cords isolated from the vertebral canal and kept in Ringer solution. The results are discussed in the light of controversial views about the occurrence of monosynaptic ventral root discharge to stimulation of the primary afferents in the amphibian spinal cord.     

The effects of cold-induced muscle spindle secondary activity on monosynaptic and stretch reflexes in the decerebrate cat.

The effects of muscle spindle secondary ending activity on the stretch reflex were studied in unanesthetized decerebrate cats. Activation of secondary endings was accomplished by reducing the muscle temperature. This has been shown to cause a sustained asynchronous discharge from secondary endings. Cooling of the medial gastrocnemius or lateral gastrocnemius-soleus muscles caused an increase in the phasic and tonic components of their stretch reflexes. Cooling of the relaxed medial gastrocnemius muscle caused similar increases in the components of the stretch reflex of the synergistic lateral gastrocnemius-soleus muscle and an increase in its monosynaptic reflex. It was concluded that the facilitatory autogenetic and synergistic effects of muscle cooling on the stretch and monosynaptic reflexes were brought about by activity in group II afferents from muscle spindle secondary endings and could not be ascribed to any other type of muscle receptor. These results support the concept of an excitatory role for the secondary endings of the muscle spindle in the stretch reflex of the decerebrate cat.     

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

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

Presynaptic mechanisms of changes in segmental responses accompanying the formation of a spinal locomotor generator in the cat

Using unanesthetized and decorticated (or decerebrated at level A 13) cats, it was found that spinalization leads to depolarization of the central terminals of primary afferents and an increase in the N₁ component of dorsal surface potential and dorsal root potential (DRP) produced by stimulating the low-threshold cutaneous and muscle afferents. Other effects include an increase in early polysynaptic responses and DRP produced by stimulation of high-threshold muscle afferents, a reduction in the intensity of interneuron activation in the nucleus interpositus mono- and polysynaptically connected with primary afferents, and a rise in the activity of n. interpositus interneurons di- and oligo-synaptically connected with afferent terminals. Changes in the opposite direction were produced by injecting DOPA into spinal animals. The connection between changes in the state of the segmental neuronal apparatus of the lumbosacral spinal cord and the level of spinal locomotor generator activity is discussed in the light of the findings obtained.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 669–678, September–October, 1986.     

GABA and Prolonged Spinal Inhibition

TWO explanations have been provided for the relatively long latency and prolonged (often exceeding 100 ms) inhibition of firing of spinal motoneurones which is caused by repetitive impulses produced by electrical or natural stimulation^1–4 in muscle and cutaneous afferent fibres. This prolonged inhibitory process is exemplified by the reduction in the amplitude of monosynaptic excitatory synaptic potentials (EPSPs) and reflexes of extensor motoneurones by tetanic stimulation of group I afferents of flexor motoneurones². In contrast with “direct” inhibition, the prolonged inhibition is not reduced by strychnine but is diminished by Picrotoxin^4,6.     

Blockade of ATP-sensitive potassium channels prevents the attenuation of the exercise pressor reflex by tempol in rats with ligated femoral arteries

We reported previously that tempol attenuated the exercise pressor and muscle mechanoreceptor reflexes in rats whose femoral arteries were ligated, whereas tempol did not attenuate these reflexes in rats whose femoral arteries were freely perfused. Although the mechanism whereby tempol attenuated these reflexes in rats whose femoral artery was ligated was independent of its ability to scavenge reactive oxygen species, its nature remains unclear. An alternative explanation for the tempol-induced attenuation of these reflexes involves ATP-sensitive potassium channels (K(ATP)) and calcium-activated potassium channels (BK(Ca)), both of which are opened by tempol. We tested the likelihood of this explanation by measuring the effects of either glibenclamide (0.1 mg/kg), which blocks K(ATP) channels, or iberiotoxin (20 or 40 μg/kg), which blocks BK(Ca) channels, on the tempol-induced attenuation of the exercise pressor and muscle mechanoreceptor reflexes in decerebrated rats whose femoral arteries were ligated. We found that glibenclamide prevented the tempol-induced attenuation of both reflexes, whereas iberiotoxin did not. We also found that the amount of protein comprising the pore of the K(ATP) channel in the dorsal root ganglia innervating hindlimbs whose femoral artery was ligated was significantly greater than that in the dorsal root ganglia innervating hindlimbs whose femoral arteries were freely perfused. In contrast, the amounts of protein comprising the BK(Ca) channel in the dorsal root ganglia innervating the ligated and freely perfused hindlimbs were not different. We conclude that tempol attenuated both reflexes by opening K(ATP) channels, an effect that hyperpolarized muscle afferents stimulated by static contraction or tendon stretch.     

Dorsal root recording relevant for mating reflexes in female rats: identification of receptive fields and effects of peripheral denervation.

Cutaneous receptive fields of dorsal roots T11 through S3 in rats were mapped by recording dorsal root multiple unit activity. The receptive fields, having the shape of transverse bands on the skin, are arranged in order according to their dorsal roots, and there are extensive overlaps between adjacent fields. Routes followed by peripheral sensory innervation of skin were also studied by observing effects of various methods of skin denervation on dorsal root responses to cutaneous stimulation. The results are discussed with respect to the somatosensory control of female rat mating reflexes.     

Role of endogenous opiates and extracellular K+ accumulation in the inhibition of frog spinal reflexes by electrical skin stimulation

Electrical skin stimulation of the hind limb (10-100 Hz, 30 s-5 min) at the intensity which leads only to the excitation of low threshold afferents depressed (for 1-30 min) the flexor reflex evoked in spinal frogs by nociceptive stimuli. The inhibition, which lasted for longer than 5 min was blocked by naloxone. Short-term poststimulation effects were associated with an increase of extracellular K+ concentration (delta [K]e) and were not blocked by naloxone. Enkephalins or morphine applied to the spinal cord surface increased the threshold for flexor reflexes while naloxone decrease their threshold. The stimulation was followed by short-term hyperpolarization of primary afferents (PAH; 1-5 min) and by depression of dorsal root potentials (DPRs) which had a similar time course to the delta [K]e, and were not blocked by naloxone. This period was frequently followed by longlasting PAH and enhancement of DRPs (5-30 min), which were abolished by naloxone. Superfusion of the isolated spinal cord with opioids produced PAH and enhanced DRPs evoked by nociceptive stimuli, while naloxone or increase of [K] in Ringer solution depolarized primary afferents and depressed DRPs. It is suggested that the antinociceptive effects of electrical stimulation of low threshold cutaneous afferents in spinal frogs involves at least two mechanisms. The short-term effect may result from delta [K]e, especially at high stimulus strength and is equally effective against noxious and non-noxious stimuli. The longlasting effects selectively affecting nociceptive transmission appear to be produced by endogenous opioids.     

Specific effects of alpha-D,L-aminoadipic acid on synaptic transmission in frog spinal cord

The sucrose gap technique was employed to investigate both synaptic and amino acid evoked responses from motoneurones or primary afferents of frog spinal cord. alpha-D,L-Aminoadipic acid (alpha-D,L-AAD) selectively antagonized responses to acidic amino acids, especially aspartate. The drug was most effective in antagonizing the polysynaptic components of synaptic potentials evoked by dorsal root or lateral column stimulation but had little effect on their monosynaptic components. The ventral root dorsal root potential which is thought to be mediated by a pathway that does not involve acidic amino acids was insensitive to alpha-D,L-AAD. These data, which were confirmed by intracellular recording from motoneurones, provided further evidence for the role of acidic amino acids in polysynaptic pathways in frog spinal cord.     

Facilitation between extensor carpi radialis and pronator teres in humans: A study using a post-stimulus time histogram method

Group I muscle afferents modulate the excitability of motor neurons through excitatory and inhibitory spinal reflexes. Spinal reflex relationships between various muscle pairs are well described in experimental animals but not in the human upper limb, which exhibits a fine control of movement. In the present study, spinal reflexes between the extensor carpi radialis (ECR) and pronator teres (PT) muscles were examined in healthy human subjects using a post-stimulus time histogram method. Electrical stimulation of low-threshold afferents of ECR nerves increased the motor neuron excitability in 31 of 76 PT motor units (MUs) in all eight subjects tested, while stimulation of low-threshold afferents of PT nerves increased the motor neuron excitability in 36 of 102 ECR MUs in all 10 subjects. The estimated central synaptic delay was almost equivalent to that of homonymous facilitation. Mechanical stimulation (MS) of ECR facilitated 16 of 30 PT MUs in all five subjects tested, while MS of PT facilitated 17 of 30 ECR MUs in all six subjects. These results suggest excitatory reflex (facilitation) between PT and ECR. Group I afferents should mediate the facilitation through a monosynaptic path.     

Reorganization of segmental responses to peripheral stimulation during fictitious scratching in cats

Segmental reflex responses of the lumbosacral region of the spinal cord to stimulation of peripheral afferents were studied in immobilized decerebrate cats before and after application of D-tubocurarine or bicuculline to the superior cervical segments, potentiating the scratch reflex, and also during fictitious scratching evoked by mechanical stimulation of the ear. Application of these substances led to inhibition of the N₁-component of the dorsal cord potential, the dorsal root potential, and polysynaptic responses in efferent nerves. The appearance of fictitious scratching was accompanied by additional tonic inhibition of these responses, against the background of which modulation of the amplitudes of the responses was observed depending on the phase of fictitious scratching. Modulation of amplitudes of monosynaptic reflexes also developed during fictitious scratching. Against the background of these results the mechanisms and physiological role of reorganization of segmental responses during activation of the spinal scratching generator are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 2, pp. 196–203, March–April, 1981.     

Synaptic activation of thoracic spinal interneurons by reticulospinal pathways

Synaptic processes of 119 thoracic spinal interneurons (T10–11) were investigated in anesthetized cats in response to stimulation of the medial and central zones of the gigantocellular nucleus in the medulla and the ventral columns of the spinal cord. Fast (90–130 m/sec) reticulospinal fibers running in the ventral column were found to produce monosynaptic or disynaptic excitation of interneurons of Rexed's layers VII–VIII, which are connected monosynaptically with group I muscle afferents, and interneurons excited both by group I muscle afferents and low-threshold cutaneous afferents. In most neurons of layer IV, connected monosynaptically with low-threshold cutaneous afferents, and in neurons of layers VII–VIII excited by afferents of the flexor reflex no marked postsynaptic processes were observed during stimulation of the reticular formation. Excitatory, inhibitory, and mixed PS Ps during activation of reticulospinal fibers were found in 14 neurons, high-threshold afferents in which evoked predominantly polysynaptic IPSPs. Seventeen neurons activated monosynaptically by reticulospinal fibers and not responding to stimulation of segmental afferents were found in the medial part of the ventral horn (layers VII–VIII).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 4, No. 6, pp. 566–578, November–December, 1972.     

Dorsal root recording relevant for mating reflexes in female rats: Identification of receptive fields and effects of peripheral denervation

Cutaneous receptive fields of dorsal roots T₁₁ through S₃ in rats were mapped by recording dorsal root multiple unit activity. The receptive fields, having the shape of transverse bands on the skin, are arranged in order according to their dorsal roots, and there are extensive overlaps between adjacent fields. Routes followed by peripheral sensory innervation of skin were also studied by observing effects of various methods of skin denervation on dorsal root responses to cutaneous stimulation. The results are discussed with respect to the somatosensory control of female rat mating reflexes.     

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.     

Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.