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.     

Investigation of the silent period by a poststimulus histogram method

The silent period after isotonic contraction induced by nerve stimulation was investigated in the human hand muscles. By using a method of poststimulus histograms of motor unit potentials and stimuli of submaximal strength for the M-response, after-hyperpolarization of the motoneurons could be excluded from the experiments. The silent period under these conditions appeared not earlier than 60 msec after stimulation; in its parameters it was similar to the silent period observed after stimulation of the nerve at subthreshold strengths for the M-response or stimulation of the skin. The experimental results thus showed that spinal effects of recurrent inhibition and spindle unloading to not occur in the hand muscles. The degree to which autogenous inhibition participates in the silent period is still uncertain. It is concluded that the role of negative feedback closed at the spinal level in the regulation of muscular contraction is not as important as has hitherto been considered on the basis of the study of the silent period.Institute of Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 10, No. 2, pp. 177–185, March–April, 1978.     

Immediate and remote postactivation effects in the human motor system

Postactivation effects consisting of protracted involuntary muscular contraction after 30–60 sec sustained voluntary effort were investigated. It was found that postactivation effects may be observed at the proximal muscles (uninvolved in the voluntary activity) following distal muscle contraction. Testing the state of muscles by the vibration activity of the muscle receptors showed that concealed changes persisting for 15–20 min occur apart from the direct postactivation effects already known. The point is made that postactivation phenomena reflecting the operation of certain central tonogenic structures activated by a voluntary effort or an increased afferent inflow may successfully be used in the study of postural control mechanisms.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 343–351, May–June, 1989.     

Peculiarities of spinal hyperreflexia after combined synchronous transection of the sciatic nerve and chordotomy in rats

Parameters of the reflex discharges evoked by spinal dorsal root stimulation were measured in rats with the sciatic nerve and spinal cord (at low thorasic level) transected five days earlier. Monosynaptic discharges in the ventral roots were found to increase after the operation; the degree of increase was significantly higher as compared with that observed after isolated transections of the spinal cord or the nerve. The combined lesion of the nerve and spinal cord could result in the appearance of high-amplitude reflex discharge components, probably of a polysynaptic nature. We concluded, from the comparison of modifications of reflex discharges, that the mechanisms underlying spinal hyperreflexia after nerve or spinal cord lesions differ considerably from each other.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 197–202, May–June, 1994.     

The Role of Endogenous Calcitonin Gene-Related Peptide in the Neurotransmitter Quantal Size Increase in Mouse Neuromuscular Junctions

Changes in parameters of spontaneous acetylcholine (ACh) quantal secretion caused by prolonged high-frequency burst activity of neuromuscular junctions and possible involvement of endogenous calcitonin gene-related peptide (CGRP) and its receptors in these changes were studied. With this purpose, miniature endplate potentials (MEPPs) were recorded using standard microelectrode technique in isolated neuromuscular preparations of m. EDL–n. peroneus after a prolonged high-frequency nerve stimulation (30 Hz for 2 min). An increase in the MEPP amplitudes and time course was observed in the postactivation period that reached maximum 20–30 min after nerve stimulation and progressively faded in the following 30 min of recording. Inhibition of vesicular ACh transporter with vesamicol (1 μM) fully prevented this “wave” of the MEPP enhancement. This indicates the presynaptic origin of the MEPP amplitude increase, possibly mediated via intensification of synaptic vesicle loading with ACh and subsequent increase of the quantal size. Competitive antagonist of the CGRP receptor, truncated peptide isoform CGRP_8–37 (1 μM), had no effect on spontaneous secretion parameters by itself but was able to prevent the appearance of enhanced MEPPs in the postactivation period. This suggests the involvement of endogenous CGRP and its receptors in the observed MEPP enhancement after an intensive nerve stimulation. Ryanodine in high concentration (1 μM) that blocks ryanodine receptors and stored calcium release did not influence spontaneous ACh secretion but prevented the increase of the MEPP parameters in the postactivation period. Altogether, the data indicate that an intensive nerve stimulation, which activates neuromuscular junctions and muscle contractions, leads to a release of endogenous CGRP into synaptic cleft and this release strongly depends on the efflux of stored calcium. The released endogenous CGRP is able to exert an acute presynaptic effect on nerve terminals, which involves its specific receptor action and intracellular cascades leading to intensification of ACh loading into synaptic vesicles and an increase in the ACh quantal size.     

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.     

Functional organization of mechanisms of presynaptic inhibition induced by stimulation of cutaneous afferents

Changes in the N₁-component and P-phase of the dorsal surface potential (DSP) of the spinal cord evoked by test stimulation of the posterior tibial nerve after conditioning stimulation of the sural nerve were investigated in anesthetized cats. The test responses were inhibited if stimulation was applied at short intervals. They then recovered to some extent, but after 1.8–2.2 msec, a further prolonged period of inhibition began. The initial inhibition was connected with occlusion of synaptic action, and the subsequent prolonged inhibition with the development of presynaptic inhibition. The latent periods of prolonged inhibition of the N₁-component and P-phase of the DSP (2 msec) were almost exactly identical, and the curves showing the diminution of the initial occlusion of these components were very similar. The results demonstrate that presynaptic inhibition of the interneurons generating the N₁-component of the DSP and of cells of the substantia gelatinosa which participate in depolarization of the presynaptic terminals of the cutaneous afferents is due to the action of depolarizing systems with similar temporal characteristics.Dnepropetrovsk State University. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 510–515, September–October, 1972.     

Contribution of homosynaptic depression to stabilization of spinal cord potentials

The following were measured during experiments on spinal anesthetized cats: firstly, variations in the amplitude of dorsal root potentials produced by applying single or regular stimuli in 120–150 trails to hindlimb cutaneous nerves and dorsal surface of the spinal cord and secondly, numbers of extracellular discharges in neurons involved in generating these potentials. A reduction in the variation between these parameters was found when applying stimulation at the rate of 0.1–5.0 Hz. The authors attribute the effect observed to the influence of homosynaptic depression.Institute of Biology, State University Commemorating 300th Anniversary of Russian-Ukrainian Reunion, Dnepropetrovsk. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 180–185, March–April, 1988.     

Distribution of myelinated and nonmyelinated nerve fibers of a cat cutaneous nerve in the spinal roots

The distribution of myelinated and nonmyelinated nerve fibers of the saphenous nerve of cats in the ventral and dorsal roots of the spinal cord was investigated by methods improving the signal—noise ratio in records of evoked responses from the nerve. The fibers of this nerve enter the spinal cord through roots of segments L_4–6. Nerve fibers with conduction velocities of between 80 and 0.38 m/sec were distributed in the dorsal roots of these segments. Four groups of nerve fibers with conduction velocities of 80–60, 40–30, 12.0–3.0, and 1.1–0.51 m/sec, possibly afferent in nature, were found in the ventral roots. The conditions of origin and detection of low-amplitude potentials in the roots of the spinal cord and the probable functional role of the nerve fibers in the ventral roots are discussed.Research Institute of Applied Mathematics and Cybernetics, N. I. Lobachevskii State University, Gor'kii. Translated from Neirofiziologiya, Vol. 7, No. 6, pp. 647–654, November–December, 1975.     

Effects of partial bulbar section on inhibition of jaw-opening reflexes induced by central gray matter stimulation in the cat

The effects of severing the spinal trigeminal tract and its caudal nucleus on high-threshold jaw-opening reflex elicited by tooth pulp stimulation were investigated during experiments on cats under chloralose-Nembutal anesthesia. Low-threshold jaw-opening reflex produced by stimulating the A--infraorbital nerve at an intensity 2–3 thresholds in relation to the most excitable fibers on this nerve was also observed, as well as suppression of these reflexes induced by central gray matter stimulation. It was found that spinal trigeminal tract section produces a 8–52% increase in high-threshold reflex. The amplitude of low-threshold reflex either remained unchanged or showed a slight tendency to rise or fall. Brief stimulation of the central gray matter produced a 100% decrease in high-threshold reflex in intact animals compared with a 40–60% decrease after section of the trigeminal tract. Protracted stimulation of the central gray brought about an 80% decline in high-threshold reflex in intact animals as against 25–30% after section. The degree to which brief stimulation of the central gray produced depression of low-threshold stimulation remained unchanged by trigeminal tract section. Protracted stimulation of the central gray matter brought about a 25–50% reduction in low-threshold reflex in intact animals and a reduction of 75% in three animals and 15–20% in four animals. This implied that the caudal nucleus of the spinal trigeminal tract exerts a more substantial influence on the process of high- than low-threshold reflex inhibition when the central gray matter is stimulated.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 362–368, May–June, 1987.     

Modulation of the Cutaneous Silent Period in the Upper-Limb with Whole-Body Instability

The silent period induced by cutaneous electrical stimulation of the digits has been shown to be task-dependent, at least in the grasping muscles of the hand. However, it is unknown if the cutaneous silent period is adaptable throughout muscles of the entire upper limb, in particular when the task requirements are substantially altered. The purpose of the present study was to examine the characteristics of the cutaneous silent period in several upper limb muscles when introducing increased whole-body instability. The cutaneous silent period was evoked in 10 healthy individuals with electrical stimulation of digit II of the right hand when the subjects were seated, standing, or standing on a wobble board while maintaining a background elbow extension contraction with the triceps brachii of ~5% of maximal voluntary contraction (MVC) strength. The first excitatory response (E1), first inhibitory response (CSP), and second excitatory response (E2) were quantified as the percent change from baseline and by their individual durations. The results showed that the level of CSP suppression was lessened (47.7 ± 7.7% to 33.8 ± 13.2% of baseline, p = 0.019) and the duration of the CSP inhibition decreased (p = 0.021) in the triceps brachii when comparing the seated and wobble board tasks. For the wobble board task the amount of cutaneous afferent inhibition of EMG activity in the triceps brachii decreased; which is proposed to be due to differential weighting of cutaneous feedback relative to the corticospinal drive, most likely due to presynaptic inhibition, to meet the demands of the unstable task.     

Effect of nociceptive stimulation of signal transmission from low-threshold cutaneous afferents in the somatosensory system

In cats anesthetized with chloralose nociceptive heating of the skin of the foot to 44–60°C led to a two- to fourfold increase in amplitude of primary cortical responses to direct stimulation of neurons of the spinocervical tract receiving information from the heated area of skin, but did not affect primary responses evoked by stimulation of axons of these neurons in the dorsolateral funiculus, and actually inhibited the response to stimulation of the nerve innervating the heated area of skin. Inhibition was accompanied by depolarization of central terminal of low-threshold fibers of this nerve: During heating the amplitude of the antidromic discharges evoked in the nerve by stimulation of its presynaptic endings in the spinal cord was increased two- to threefold. After abolition of presynaptic depolarization with picrotoxin (0.2–0.7 mg/kg, intravenously) or as a result of asphyxia, nociceptive heating acquired the ability to facilitate primary responses arising as a result of stimulation of the nerve also. The amplitude of the responses was increased under these circumstances by 3–20 times. It is concluded that acute nociceptive stimulation causes such powerful presynaptic inhibition of impulse transmission from low-threshold fibers of the cutaneous nerve that it virtually abolishes the facilitating effect of nociceptive impulses on sensory neurons of the spinal cord. It is suggested that it is this inhibitory mechanism which prevents the development of hyperalgesia during acute nociceptive stimulation.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 6, pp. 621–627, November–December, 1981.     

Excitation of cat spinal cord dorsal column fibers during stimulation of different fiber groups of cutaneous and somatic nerves

The effects of electrically stimulating different groups of nerve fibers supplying the skin and muscle on evoked potentials in cat spinal cord dorsal columns were studied. Significant differences in the configuration of dorsal column potentials recorded in response to stimulation of these nerves were found. It was shown that cutaneous nerve unmyelinated fibres were connected to unmyelinated dorsal column fibers. In addition, excitation of cutaneous C-fibers lead to activation of dorsal column fibers with the maximum conduction velocity. The somatic nerve was only connected to myelinated dorsal column fibers, and excitation of its non-myelinated fibers did not cause other types of dorsal column fibers to be activated. It is suggested that the acceleration of cutaneous signal transmission in the dorsal column system may be brought about by the necessity for rapid warning of potentially harmful stimuli.Medical Institute, Russian Federation Ministry of Public Health, Nizhny Novgorod. Translated from Neirofiziologiya, Vol. 24, No. 5, pp. 625–635, September–October, 1992.     

Synaptic potentials of motoneurons of the masseter muscle

Postsynaptic potentials of 93 motoneurons of the masseter muscle evoked by stimulation of different branches of the trigeminal nerve were studied. Stimulation of the most excitable afferent fibers of the motor nerve of the masseter muscle evoked monosynaptic EPSPs with a latent period of 1.2–2.0 msec, changing into action potentials when the strength of stimulation was increased. A further increase in the strength of stimulation produced an antidromic action potential in the motoneurons with a latent period of 0.9 msec. In some motoneurons polysynaptic EPSPs and action potentials developed following stimulation of the motor nerve to the masseter muscle. The ascending phase of synaptic and antidromic action potentials was subdivided into IS and SD components, while the descending phase ended with definite depolarization and hyperpolarization after-potentials. Stimulation of cutaneous branches of the trigeminal nerve, and also of the motor nerve of the antagonist muscle (digastric) evoked IPSPs with a latent period of 2.7–3.5 msec in motoneurons of the masseter muscle. These results indicate the existence of functional connections between motoneurons of the masseter muscle and its proprioceptive afferent fibers, and also with proprioceptive afferent fibers of the antagonist muscle and cutaneous afferent fibers.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 262–268, November–December, 1969.     

Analysis of long-latency components of field potentials evoked by stimulation of the cerebral cortex and nerves in the cerebellar paramedian lobule

Field potentials evoked in the graunular layer of the cerebellar paramedian lobule of unanesthetized cats in response to stimulation of the sensomotor cortex and limb nerves contained slow negative waves, appearing after a long latent period, which were generated by granule cells. In the case of nerve stimulation this component was recorded both inside and outside the projection zone of the corresponding limb. Cortical stimulation by single stimuli or series of stimuli not more than 1.8–2.5 times above threshold strength led to the appearance of evoked potentials only inside the corresponding projection zone. The long-latency component of field potentials evoked by cerebral stimulation followed high frequencies of repetitive stimulation and was less sensitive to the action of barbital anesthesia than the analogous component of potentials evoked by nerve stimulation. In the case of combined cerebral and nerve stimulation the long-latency components underwent summation. It is concluded that mossy fibers of slowly-conducting spino- and cerebrocerebellar tracts innervate different granule cells in the cerebellar cortex.Institute of Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 379–385, July–August, 1982.     

Mechanism of inhibition following reflex discharge in spinal cord interneurons

Using the method of microelectrode (intracellular and extracellular) recording, the mechanism of inhibition following reflex discharge in interneurons of the lumbosacral section of the spinal cord of cats on activation of cutaneous and high-threshold muscle afferents was studied. It was shown that the postdischarge depression of the reflex responses 10–20 msec after the moment of activation of the neuron is due to afterprocesses in the same neuron and presynaptic pathways. The depression of spike potentials from the 20th to the 100th msec is produced by inhibitory postsynaptic potentials (IPSP). During the development of IPSP the inhibition of spike potentials can be due to both a decrease of the depolarization of the postsynaptic membrane below the critical threshold and a decrease of sensitivity of the cell membrane to the depolarizing action of the excitatory postsynaptic potential (EPSP). At intervals between the stimuli of 30–100 msec the duration of EPSP after the first stimulus does not differ from that after the second stimulus. Hence, it is suggested that the presynaptic mechanisms do not play an essential part in this type of inhibition of interneurons. The inhibition following the excitation favors the formation of a discrete message to the neurons of higher orders.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 3–9, January–February, 1970.     

EPSPs of masseter motoneurons evoked by stimulation of low-threshold infraorbital nerve afferents in cat

Stimulation of the infraorbital nerve at strengths 1.4–2.5 times higer than the threshold of excitation of A fibers in cats anesthetized with chloralose and pentobarbital evoked EPSPs with an amplitude up to 3.0 mV and a duration of 9–15 msec in 69% of masseter motoneurons after 1.5–3.0 msec. These EPSPs were complex and formed by summation of simpler short-latency and long-latency EPSPs. The short-latency EPSPs appeared in response to infraorbital nerve stimulation at 1.1–1.5 thresholds and had a slow rate of rise (2.5–4.5 msec, mean 3.7±0.4 msec), low amplitude (under 2.0 mV), and short duration (5–6 msec). Their latent period varied from 1.5 to 3.0 msec (mean 2.1±0.2 msec). The shortness of the latent period and its constancy during stimulation of the nerve at increasing strength, and also the character of development of facilitation and inhibition of the EPSP during high-frequency stimulation suggests that these EPSPs are monosynaptic. The slow rate of rise suggested that these EPSPs arise on distal dendrites of the motoneurons. Long-latency EPSPs appeared 7–9 msec after stimulation of the infraorbital nerve at 1.1–1.5 thresholds. Their amplitude reached 1.5–2.0 mV and their duration 7–9 msec. The long duration of the latent period combined with low ability to reproduce high-frequency stimulation (up to 30/sec) points to the polysynaptic origin of these EPSPs.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 6, pp. 583–591, November–December, 1977.     

Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation

Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20–100), 100 (20–120), and 120 (50–200) µA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synaptic components of the thalamic evoked potential was 50–60% (P<0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 467–475, September–October, 1976.     

Histochemically demonstrable catecholamines and cholinesterases in nerve fibres of rat dorsal skin

Summary Histochemically demonstrable cholinesterases of rat skin and cutaneous nerves hydrolyze acetylthiocholine iodide and butyrylthiocholine iodide. Cholinesterase activity of the skin was located in the epidermis, in the hair follicles at the level of the sebaceous glands, in adjacent parts of the sebaceous glands, in erector pili muscles and their nerves, in cutaneous and subcutaneous nerves and nerve trunks, including some nerves accompanying cutaneous blood vessels, and in the membranes of fat cells. No encapsulated nerve endings were found. In the nerves of erector pili muscles there was some neurilemmal non-specific cholinesterase activity, demonstrated in the presence of 10^–5 M BW 284C 51, and specific acetylcholinesterase activity resistant to 10^–5 M iso-OMPA. The cholinesterase activity in other cutaneous nerves was inhibited by 10^–5 M iso-OMPA but was resistant to 10^–5 M BW284 C 51, thus representing mainly non-specifc cholinesterase (nsChE) activity.The adrenergic nerves of the dorsal skin, as revealed by glyoxylic acid-induced fluorescence (GIF), were located in association with erector pili muscles and surrounded arteries and arterioles. Small fluorescent nerves were situated in subcutaneous nsChE-positive nerve trunks.Using GIF and cholinesterase techniques performed either simultaneously or consecutively, it was found that the nsChE-positive, probably sensory, nerves accompanying blood vessels were fewer in number than the fluorescent adrenergic nerves and ran a course independent of them. No cholinesterase reaction was seen in the fluorescent adrenergic nerves when short incubation times were used. When the incubation time was prolonged overnight, the nsChE reaction closely followed the course of fluorescent adrenergic nerves.     

电刺激大鼠脊神经皮支对远距离机械感受单位电活动的影响

实验采用分离神经细束的方法,观察逆行电刺激大鼠脊神经背侧皮支后,在相距较远的神经细束上记录到的Aδ和C类机械感受单位电活动的变化。刺激T9脊神经背侧皮支,在T12神经细束上记录到59.3%（16/27）的Aδ和71.2%(37/52）的C类单位在刺激后90～120s放电显著增加。刺激T8脊神经背侧皮支,在T12神经细束上记录到47.8%(11/23）的Aδ单位和36.6%(15/41）的C类单位在刺激后120～150s放电显著增加。大多数单位（18/23）的机械感受阈值在电刺激远距离脊神经背侧皮支后降低。结果表明,逆行电刺激外周感觉神经,可以使相距较远的Aδ和C类机械感受单位致敏,其传入放电增加。