Modulation of Short-Latency Afferent Inhibition Depends on Digit and Task-Relevance

Short-latency afferent inhibition (SAI) occurs when a single transcranial magnetic stimulation (TMS) pulse delivered over the primary motor cortex is preceded by peripheral electrical nerve stimulation at a short inter-stimulus interval (∼20–28 ms). SAI has been extensively examined at rest, but few studies have examined how this circuit functions in the context of performing a motor task and if this circuit may contribute to surround inhibition. The present study investigated SAI in a muscle involved versus uninvolved in a motor task and specifically during three pre-movement phases; two movement preparation phases between a “warning” and “go” cue and one movement initiation phase between a “go” cue and EMG onset. SAI was tested in the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles in twelve individuals. In a second experiment, the origin of SAI modulation was investigated by measuring H-reflex amplitudes from FDI and ADM during the motor task. The data indicate that changes in SAI occurred predominantly in the movement initiation phase during which SAI modulation depended on the specific digit involved. Specifically, the greatest reduction in SAI occurred when FDI was involved in the task. In contrast, these effects were not present in ADM. Changes in SAI were primarily mediated via supraspinal mechanisms during movement preparation, while both supraspinal and spinal mechanisms contributed to SAI reduction during movement initiation.     

Spinal cord sensory systems after neonatal capsaicin

Animals with a severe reduction in the number of afferent C-fibres as a consequence of neonatal administration of capsaicin, exhibit a number of neurological and behavioral deficits including increased nociceptive thresholds, altered somato-visceral and viscero-visceral reflexes, depressed cardiovascular and respiratory reflexes and changes in the organisation of spinal cord sensory systems. The reduction in the number of C-fibres produced by neonatal capsaicin does not cause a decrease of similar magnitude in the number of dorsal horn cells driven by the surviving C-fibres. Twenty-two per cent of dorsal horn neurones in capsaicin treated animals respond to electrical stimulation of the surviving afferent C-fibres: a reduction of only 50% from control values. Inhibitory controls on afferent C-fibre evoked responses of dorsal horn neurones are weaker in capsaicin treated rate than in control animals. The cutaneous receptive fields of some dorsal horn neurones can increase in size following stimulation of afferent C-fibres. Tonic descending inhibition on C-fibre evoked responses of dorsal horn neurones is reduced in capsaicin treated rats: fewer neurones show tonic descending inhibition in these animals and those that do are subjected to less powerful inhibitions than similar neurones from control animals. However, some central inhibitory mechanism are unchanged after neonatal capsaicin treatment, specially those that do not involve afferent C-fibres. We suggest that the nervous system develops central inhibition in response to and directed towards the excitations mediated by its afferent drives. Therefore reduced central inhibition in response to a decreased number of afferent C-fibres can compensate for the lost capacity in the signalling of peripheral noxious events.     

Neurogenic contractions of the rat tail artery under isobaric conditions: effect of transmural pressure and function of the endothelium]

In stimulation of the rat nerve with a modulated sine pattern, an increase in the modulating frequency from 0.03 to 0.15 Hz diminished the latency between the stimulating signals and changes in the vessel resistance as well as the amplitude of the flow oscillations, but did not affect tonic contractions of the vessel. A reduction of transmural pressure from 80 to 40 mm Hg increased both the tonic and the phasic components of the vessel contraction. Following the endothelium removal no change in the response latency occurred. The data obtained suggest that, during a rhythmic neurogenic influence, the vascular endothelium may work as an "amplifier" of the vessel's phasic contractions.     

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。     

Dissociation induced by voluntary movement between two different components of the centro-parietal P40 SEP to tibial nerve stimulation

Whether the two earliest cortical somatosensory evoked potentials (SEPs) to tibial nerve stimulation (N37 and P40) are generated by the same dipolar source or, instead, originate from different neuronal populations is still a debated problem. We recorded the early scalp SEPs to tibial nerve stimulation in 10 healthy subjects at rest and during voluntary movement of the stimulated foot. We found that the P40, which reached its highest amplitude on the vertex at rest, changed its topography during movement, since its amplitude was reduced much more in the central than in the parietal traces. These findings suggest that two different components contribute to the centro-parietal positivity at rest: (1) the P37 response, which is parietally distributed and is not modified by movement, and (2) the `real' P40 SEP, which is focused on the vertex and is reduced in amplitude during voluntary movement. Since, also, the N37 response did not vary its amplitude under interference condition, it is possible that the N37 and P37 potentials are generated by the same dipolar source. Other later components, namely P50 and N50, were significantly reduced in amplitude during foot movement. Lastly, the subcortical P30 far-field remained unchanged and this suggests that the phenomenon of amplitude reduction during movement (i.e. gating) occurs above the cervico-medullary junction.     

Polarization of primary afferent terminals in the lumbar spinal cord during fictitious locomotion

Changes in electrical polarization of primary afferent terminals in the lumbosacral portion of the spinal cord were investigated during fictitious locomotion in immobilized decorticated and spinal cats. Fictitious locomotion was accompanied by stable hyperpolarization of the afferent terminals, against the background of which they were periodically depolarized in rhythm with efferent activity. These tonic and phasic changes were observed in terminals of all groups of afferent fibers tested: cutaneous and muscular (Ia and Ib). Periodic in-phase depolarization was carried out in different ipsilateral segments of the lumbosacral enlargement. During ficitious galloping changes in depolarization of the primary efferents were in phase on different sides; during fictitious walking, these periodic changes were out of phase. On the basis of these results the physiological importance of changes in electrical polarization of primary afferent terminals of the spinal locomotor generator is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 481–489, September–October, 1980.     

Mechanism of hypothalamic control of cardiac component of sinus nerve reflex.

The modulatory influence of hypothalamic structures on sinus nerve induced bradycardia was investigated in anaesthetized cats. Stimulation of the hypothalamic defence area inhibits the bradycardia produced by sinus nerve stimulation both in intact animals and also in animals with the spinal cord sectioned at C1 or C6. This inhibition was accompanied in the normal animal by an increased sympathetic discharge and by a sustained inspiration or tachypnoea. The same respiratory effects were noted in a spontaneously breathing C6 spinal animal, while an artificially ventilated C1 spinal animal still displayed a powerful central inspiratory drive in its recurrent laryngeal electroneurogram. The presence of central inspiratory activity was found to be an absolute impediment to the development of bradycardia. If this activity was eliminated by simultaneous stimulation of the superior laryngeal nerve, it was possible to obtain bradycardia during combined sinus nerve and hypothalamic defence area stimulation, though this bradycardia was modified by the presence of sympathetic discharge. The level of sympathetic neural discharge affects the magnitude of the bradycardia produced by sinus nerve stimulation. The bradycardia was less with normal or augmented level of sympathetic activity and was greater if this activity was reduced or absent. A lesion just caudal to the mammillary bodies disclosed a tonic hypothalamic influence both on respiration and on sympathetic discharge; stimulation of the sinus nerve produced a much more powerful bradycardia after the lesion. The existence of a respiratory "gate" through which afferent stimuli pass on their way to the nucleus ambiguus, and which can be operated by the hypothalamic defence and depressor areas, is postulated and discussed.     

Active selection of afferent information as the basic principle of peripheral correction of the activity of spinal rhythmic movement generators

This paper summarizes information obtained in the experimental study of the dynamics of polarization of central primary afferent endings and modifications of segmental responses to afferent stimuli during fictitious locomotion and fictitious scratching in immobilized, decorticated, decerebrate, and spinal cats. Fictitious locomotion was accompanied by tonic hyperpolarization, fictitious scratching by tonic depolarization of central primary afferent endings. Against the background of these long-lasting changes in primary afferent depolarization, it exhibited periodic changes in the rhythm of efferent activity. Periodic changes of depolarization were virtually in phase in different ipsilateral segments of the lumbosacral enlargement. Data on groups of afferent fibers in whose central endings tonic and phasic changes of polarization took place. The appearance of fictitious locomotion was accompanied by a tonic increase, and of fictitious scratching by tonic inhibition of several evoked segmental responses. These tonic changes were a background against which segmental responses were modulated in step with the working rhythm of the locomotion and scratching generators. Many of the changes in evoked segmental responses were shown to be based on modulation of polarization of central endings of primary afferents by locomotion and scratching generators. It is concluded that active tonic and phase-dependent selection of incoming afferent information is effected through modulation of presynaptic inhibition of the generator. The role of this selection in peripheral collection of activity of locomotion and scratching generators is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 343–353, May–June, 1984.     

Local,exendin-(9-39)-insensitive,site of action of GLP-1 in canine ileum

Glucagon-like peptide-1 (GLP-1) modulates glucose levels following a meal, including by inhibition of gastric emptying and intestinal transport. Intra-arterial injection of GLP-1 into the gastric corpus, antrum, or pylorus of anesthetized dogs had no effect on the contractile activity of the resting or neurally activated stomach. GLP-1 injected intra-arterially inhibited intestinal segments when activated by enteric nerve stimulation but not by acetylcholine. Isolated ileum segments were perfused intra-arterially, instrumented with strain gauges to record circular muscle activity and with subserosal electrodes to stimulate enteric nerves. GLP-1 caused concentration-dependent inhibition of nerve-stimulated phasic but not tonic activity. This was absent during TTX-induced activity and partly prevented by N(G)-nitro-L-arginine. Exendin-(9-39), the GLP-1 antagonist, had no intrinsic activity and did not affect the actions of GLP-1. Capsaicin mimicked the effects of GLP-1 and may have reduced the effect of subsequent GLP-1. GLP-1 may mediate paracrine action on afferent nerves in the canine ileal mucosa using an unusual receptor.     

Certain functional connections of neurons control the walking of the cockroach Periplaneta americana

On isolated abdominal nervous chain of the cockroach studies have been made of the responses of motoneurones of the thoracic ganglion to electrical stimulation of afferent axons of the leg nerve under normal conditions and during application of an anticholinesterase drug, GD-7. Depending on the type of stimulated axons, monosynaptic response, as well as polysynaptic phasic and tonic responses of motoneurones were recorded. A scheme of activation of motoneurones is suggested which evokes slow contractions of muscles in cockroach extremities.     

Participation of nonsegmentary neurons of the spinal cord in execution of presynaptic control

Experiments were carried out on cats six days after complete transection of the spinal cord. Cord dorsum potentials (CDP) were recorded in the vicinity of the third lumbar segment during stimulation of the isolated dorsolateral funiculus (DLF). The CDP consist of a rapid monophasic potential (which apparently reflects antidromic excitation of the cells of Clarke's column) and two subsequent slow negative waves, which are replaced by a long positive oscillation. In form, time characteristics, and behavior during thythmic stimulation, this potential differs considerably from the CDP recorded during stimulation of the afferent nerves. The presence of a positive phase of the CDP indicates that stimulation of the DLF evokes primary afferent depolarization (PAD). Stimulation of the DLF causes inhibition of the CDP evoked by stimulation of the afferent nerve. The time course of this inhibition corresponds to the time course of presynaptic inhibition. It is demonstrated that stimulation of the afferent nerve (n. femoralis) inhibits slow components of the CDP evoked by stimulation of the DLF. This inhibition reaches a maximum at the 16th millisecond; its duration exceeds 300 msec. Stronger and more prolonged inhibition of the same components is observed when both the conditioning and the testing stimuli are administered to the DLF. Since primary afferents do not take part in CDP emergence during stimulation of the DLF, it may be hypothesized that the observed inhibition develops as a result of depolarization of interneuron axon terminals.Dnepropetrovsk State University. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 520–527, September–October, 1970.     

Tonic-to-phasic shift of lumbo-pelvic muscle activity during 8 weeks of bed rest and 6-months follow up.

Prior motor control studies in unloading have shown a tonic-to-phasic shift in muscle activation, particularly in the short extensors. Tonic muscle activity is considered critical for normal musculoskeletal function. The shift from tonic-to-phasic muscle activity has not been systematically studied in humans in unloading nor at the lumbo-pelvic (LP) region. Ten healthy young male subjects underwent 8 wk of bed rest with 6-mo follow up as part of the "Berlin Bed-Rest Study." A repetitive knee movement model performed in the prone position is used to stimulate tonic holding LP muscle activity, as measured by superficial EMG. Tonic and phasic activation patterns were quantified by relative height of burst vs. baseline electromyographic linear-envelope signal components. Statistical analysis shows a shift toward greater phasic activity during bed rest and follow up (P < 0.001) with a significant interaction across muscles (P < 0.001) specifically affecting the short lumbar extensors. These changes appear unrelated to skill acquisition over time (P all > or = 0.196). This change of a shift from tonic LP muscle activation to phasic is in line with prior research on the effects of reduced weight bearing on motor control.     

Effects of a new analgesic agent, D57, on sodium currents in afferent neurons of the rat ganglia

We studied the effects of a new analgesic agent, D57 (a pyrrolimidazol derivative), on sodium currents in isolated afferent neurons of the trigeminal and spinal ganglia of rats. It is demonstrated that D57 exerts both tonic and phasic effects on sodium currents. In the neurons of a nociceptive system influenced by D57, phasic blocking provides suppression of more than 50% of the currents that persisted after the development of tonic blocking. At the same time, in the neurons supposedly belonging to other afferent systems, the contribution of phasic blocking was only about 20%. We hypothesize that high intensity of phasic blocking of sodium ion currents in the neurons of the nociceptive system represents a factor responsible for analgesic properties of D57.     

Responses of caudate neurons to clicks in chronic experiments on cats

Spontaneous and evoked unit activity in response to repeated application of clicks at a frequency of 0.3–2.0 Hz in the caudate nucleus was studied by an extracellular recording technique in chronic experiments on cats. Four types of spontaneous unit activity in the caudate nucleus were distinguished. Altogether 44% of neurons tested responded by changes in spontaneous activity to clicks. Five types of responses of caudate neurons to clicks were discovered: phasic excitation, phasic inhibition, tonic activation, tonic inhibition, and mixed tonic responses; the commonest type was tonic activation. During prolonged stimulation by clicks extinction of the phasic responses was not observed. Complete or partial extinction of tonic responses in the course of frequent repetition of stimulation was observed in 33% of responding neurons. The question of possible convergence of specific and nonspecific influences on caudate neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 28–35, January–February, 1980.     

Participation of interoceptive afferent impulses in polymodal responses of superior collicular neurons in the cat

Experiments on immobilized, unanesthetized cats showed that interoceptive afferent impulses reaching the brain via the vagus nerves evoke marked responses in, on average, 43% of superior collicular neurons. Both excitatory and inhibitory effects were observed. The latter were found more often during single stimulation of the vagus nerve. In half of the cases the inhibitory responses were characterized by the development of initial inhibition, clearly limited in time to between 180 and 1700 msec. Changes in spike activity of 60% of units were tonic in character. The onset of phasic responses with an initial period of activation was observed in only 9–11% of neurons. The number of these cells and also the total number of responding neurons were greater than when series of stimuli were applied to the vagus nerve. In individual cells during prolonged repetitive stimulation of the nerve gradual weakening of the responses took place. Somatic stimulation evoked mainly the development of phasic responses of excitatory type. Most of the neurons tested were bimodal and often the temporal structure of their responses was determined by the modality of the stimulus applied. The functional role of the changes discovered in spontaneous activity of superior collicular neurons under interoceptive influences and the central mechanisms of realization of such influences on the activity of the neuronal system in this brain structure are discussed.Ivano-Frankovsk Medical Institute, Ministry of Health of the Ukrainian SSR. Translated from Neirofiziologiya, Vol. 10, No. 6, pp. 590–596, November–December, 1978.     

Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

Cholinergic mechanisms related to REM sleep. III. Tonic and phasic inhibition of monosynaptic reflexes induced by an anticholinesterase in the decerebrate cat

The depression of the postural activity induced by intravenous injection of eserine sulphate (0.1 mg/kg), an anticholinesterase, has been studied in precollicular decerebrate cats. The extensor and flexor monosynaptic reflexes elicited by single shock stimulation of the GS, P1-FDHL and DP nerves are tonically depressed during the episodes of postural atonia induced by the anticholinesterase. A further phasic depression of the monosynaptic reflexes occurs during the bursts of rapid eye movements (REM) typical of these episodes. These changes in spinal reflex activity closely resemble the tonic depression of the spinal reflexes described in the unrestrained cats during the desynchronized sleep as well as the phasic depression of the spinal reflexes characteristic of the hypnic bursts of REM. Results obtained after spinal cord section indicate that both the tonic and the phasic depression of the spinal reflexes induced by eserine are due to active inhibitory influences originating from supraspinal structures. A complete bilateral destruction of the vestibular nuclei or limited to the medial and descending vestibular nuclei abolishes not only the cholinergically induced bursts of REM, as reported in a previous paper, but also the related phasic depression of the monosynaptic reflexes. These findings can be related with previous observations showing that a bilateral lesion of the vestibular nuclei abolishes the REM bursts of desynchronized sleep, as well as the related phasic inhibition of the spinal reflexes. The tonic depression of the monosynaptic reflexes induced by the anticholinesterase, on the other hand, remains unmodified by this vestibular lesion. This depression, therefore, can be attributed to supraspinal descending inhibitory volleys originating from extravestibular structures.     

刺猬胸前神经传入活动的来源及皮层代表区分布

为探讨冬眠刺猬皮肌的紧张性控制,本工作研究了支配皮肌的胸前神经(VTN)的传入活动的来源和皮层代表区的分布。VTN的传入冲动来自皮肌本体感受器,传入纤维径C_6—T_2背根入脊髓,与同部位的皮肤感觉相分离,后者经相应节段的皮神经传入。电刺激VTN引起的皮层诱发电位反应位于新皮层外侧面的中间部,相当于Woolsey的S-Ⅱ区内,与桡神经和坐骨神经的代表区有重叠,而在S-Ⅰ区没有记录到反应。     

Changes in presynaptic processes during tonic sub-threshold activation of spinal scratch generator in the cat

It was found during experiments on immobilized decerebrate (at intracollicular level) cats that tonic sub-threshold activation of the spinal generator of scratching action (following application of tubocurarine or bicuculline to segments C₁-C₂) was accompanied by depolarization of primary afferent terminals, a reduction in the N₁ component of dorsal surface potential produced by stimulating the cutaneous afferents, and a reduction in the amplitude of dorsal root potentials and lead-phase polysynaptic response produced in motoneurons by stimulating the cutaneous and muscle afferents. A rise or a reduction in the activity of interneurons belonging to the interstitial nucleus connected respectively mono- and di-(oligo)synaptically with the afferents occurred in parallel with this. Spinalization produced the same changes in reverse in the animal. By administering DOPA to the spinal animal, a comparison could be made of changes occurring in the state of the segmental apparatus of the lumbar section of the spinal cord during tonic sub-threshold activation of spinal scratch generators and locomotor movements.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 2, pp. 236–243, March–April, 1987.     

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.