Effects of repetitive stimulation of the locus coeruleus on spinal inhibitory responses to suprasegmental stimulation in cats

Effects of repetitive stimulation of the locus coeruleus on spinal responses to activation of cortico-, reticulo-, and vestibulospinal tracts were studied in decerebellate cats anesthetized with chloralose. Descending influences of these structures were assessed from changes in amplitude of extensor and flexor monosynaptic discharges or from the magnitude of postsynaptic potentials recorded from the corresponding motoneurons. Stimulation of the motor cortex or modullary reticular formation as a rule evoked two-component inhibitory responses in extensor motoneurons and excitatory-inhibitory responses in flexor motoneurons. Stimulation of locus coeruleus effectively depressed the amplitude of the late component and, to a lesser degree, that of the early component of inhibition arising after stimulation of the cerebral cortex or reticular formation. During stimulation of the locus coeruleus no marked changes were found in inhibitory responses evoked by vestibulospinal influences in flexor motoneurons, and also in excitatory responses arising after stimulation of the above-mentioned descending pathways in both groups of motoneurons.     

Changes in segmental reflex responses during stimulation of locus coeruleus and potentiation of the action of catecholamines

Repetitive stimulation of the locus coeruleus (up to 150 µA in strength) was accompanied by marked weakening of the inhibitory action of flexor reflex afferents and of the reciprocal inhibitory action on extensor motoneurons. Meanwhile stimulation of this sort had no significant effect on direct inhibition of flexor and extensor motoneurons, on the facilitatory action of flexor reflex afferents and the reciprocal inhibitory action on flexor motoneurons and also on dorsal root potentials. Intravenously injected pyrogallol had a similar action, but its effect was much weaker after spinalization of the animals or blocking of spinal cord conduction by cold. Enhancement of the monosynaptic reflex, which also was observed after injection of pyrogallol, was characterized by different temporal parameters; the intensity of this effect was unaffected both by spinalization and by cold block. These data, and also the results of experiments with partial divisions of the spinal cord, suggest that the effects of stimulation of the locus coeruleus are the result of activity of a descending coerulo-spinal tract, running in the ventral quadrant of the spinal cord.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 1, pp. 39–47, January–February, 1981.     

Effect of repetitive stimulation of the locus coeruleus on spinal inhibition evoked in cats by activation of flexor reflex afferents

Repetitive stimulation of the locus coeruleus with a frequency of 40 Hz and strength of 50–150 µA in decerebellated cats anesthetized with chloralose was accompanied by a decrease in the inhibitory action of flexor reflex afferents (FRA) on the extensor monosynaptic reflex. This effect, which appeared after 600 msec, reached a maximum 1500–1700 msec after the beginning of repetitive stimulation. A minimum of 7–10 stimuli was needed to evoke the effect. After the end of stimulation the inhibitory action of FRA was not fully restored until after 2–3 sec. During application of a single stimulus or a short high-frequency series of stimuli of the same strength to the locus coeruleus no such effect was found. An increase in the strength of stimulation in that case was accompanied by activation of adjacent more rapidly conducting structures. The advantage of repetitive stimulation for detecting effects of slowly-conducting brain structures is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 2, pp. 187–195, March–April, 1981.     

Admissibility of simplifications when modeling the neurotransmitter spillover and postsynaptic responses evoked by repetitive stimulation

It is shown that some assumptions used in a number of studies dealing with the modeling of neurotransmitter spillover (in particular concerning geometry of the space that surrounds synapses, the number of neighboring active zones or synapses, and their space distribution) may markedly distort an estimation of the contribution of currents arising from distant release sites to evoked postsynaptic currents. In the case of experimental measurements of these currents, some unknown quantities may not be estimated entirely correctly with the help of simplified models. Transition from a stochastic model of generation of postsynaptic responses evoked by trains of stimuli to a simpler deterministic model usually does not lead to identical results. Neirofiziologiya/Neurophysiology, Vol. 39, No. 1, pp. 126–132, March–April, 2007.     

After-effects of repetitive stimulation in spinal neurons

Spontaneous activity of interneurons before and after repetitive stimulation at 0.1–0.5/sec was recorded in acute experiments on spinal cats and kittens. Using the dynamic selective correlation method a search was made for areas of spontaneous activity with the same distribution of action potentials in time as in the averaged evoked response to a single stimulus. In the case of some neurons portions of the background which correlate reliably in structure with the evoked response repeated at an interval equal to or a multiple of the interval of stimulation. Reproduction of the rhythm of stimulation in the spontaneous activity is intensified with an increase in the total duration of preceding stimulation with the same input and shows positive correlation with the degree of posttetanic potentiation. The facts obtained are evidence of prolonged after-processes in spinal neurons.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 272–280, May–June, 1973.     

ATP-敏感钾通道和内源性腺苷参与刺激蓝斑引起的脊髓抗痛作用

根据蓝斑刺激可以通过脊髓下行性去甲肾上腺素能纤维阻断由背角上传到束旁核神经元的伤害性放电的事实,本实验用脊髓鞘内给予相应工具药的方法,进一步分析了上述下行性抑制作用在脊髓背角中阻止伤害性传入信号向上传递的可能机制,结果发现：（1）鞘内注入ATP-敏感钾通道阻断剂格列苯脲或腺苷受体拮抗剂氨茶碱,均可以阻断或取消刺激蓝斑引起的对束旁核伤害性放电的抑制作用;（2）鞘内注入ATP-钾通道激动剂nic-orandil或腺苷受体激动剂5‘-N-ethylcarboxamido-adenosine(NECA）,都可抑制束旁核神经元的伤害性放电;（3）鞘内注入氨茶碱可阻断鞘内注入nicorandil引起的束旁核痛放电的抑制,再鞘内注入格列苯脲不能阻断鞘内注入NE-CA引致的束旁核痛放电的抑制。这些结果提示：（1）蓝斑刺激在脊髓背角中抑制痛信号的上传,要有ATP-敏感钾通道的激活和内源性腺苷的释放为中介;（2）ATP-敏感钾通道的激活发生在腺苷的释放之前。     

蓝斑对迷走—心血管反射的影响

实验用家兔３６只,采用低频和高频电流刺激颈部迷走神经中枢端,建立迷走－减压和迷走－升压反射,两种频率电刺激均导致肾交感神经传出活动减少。以迷走－血压反射和迷走－交感反射为指标,连续电流刺激蓝斑或ＬＣ微量注射谷氨酸钠均抑制迷走－血压反射和迷走－交感反射。     

Differentiated pressor and sympathetic responses to dual brain stimulation: ventromedial hypothalamus versus locus coeruleus

Sensitivity of the ventromedial hypothalamus (VMH) to electrical stimulation was compared with that of the locus coeruleus (LC) in urethane-anesthetized rats. Based not only on current strengths required to elicit threshold effects, but also on magnitude of pressor responses to suprathreshold stimulation, the LC was consistently more sensitive than the VMH. Despite this greater pressor sensitivity, splanchnic nerve firing increased almost equally upon stimulation of either brain area. Similar comparisons made in other rats following bilateral adrenalectomy or pretreatment with a vasopressin antagonist showed no significant alteration of pressor and sympathetic responsiveness to stimulation of either the LC or the VMH. When frequency of neural firing was recorded from a lumbar sympathetic trunk instead of the splanchnic nerve, increases in sympathetic nerve activity produced by LC stimulation were significantly larger than those produced from the VMH. The results suggest that greater pressor sensitivity of the LC is due, at least in part, to stronger constriction in vascular beds innervated by the lumbar sympathetic chains.     

Influence of asphyxia upon the responses of spinal motoneurons

Observations have been made upon asphyxial and postasphyxial changes in the electrical responses of motoneurons to antidromic stimulation. Analysis has been aided by the use of a simple method for locating conduction blocks in the circumstances of volume conduction. Asphyxiation has been produced by suspending artificial ventilation. Regular practice has been to restore ventilation immediately after complete conduction block is established. This has permitted study of the postasphyxial state, but not of the effects of prolonged asphyxiation with the latter of which this paper is not concerned. With asphyxiation produced in the manner outlined a latent period of approximately 1 minute precedes the onset of asphyxial change. The initial change, to judge by the work of others (6, 7), is beginning central depolarization. At the same time there is a severe loss of somatic after-potential (Fig. 1). Through this loss the dendrites acquire the ability to carry two volleys in rapid succession (Fig. 13). These changes appear to reach completion within approximately 30 seconds. There follows a period of convulsive activity during which reciprocal amplitude changes in the response of axons and dendrites prove that a fluctuation in somatic responsivity is taking place (Fig. 11). Intermittent impulse discharge in ventral roots is seen (Fig. 1). Conduction block may be developing slowly throughout the period of convulsive activity (Fig. 11). Frequently there is a rather definite instant at which convulsive activity ceases and a rapid development of block begins. Usually the recorded amplitude of the dendritic response then increases to a peak (the preterminal increment) before final disappearance (Figs. 9 to 11, 13 to 15). A variety of reasons has been advanced to show that this preterminal increment represents not increased response, but rather a developing block (Figs. 11 to 13). When fully established, asphyxial block is located at the junction of the initial and myelinated axon segments (Figs. 5 to 7). It is a depolarization or cathodal block. On restoring ventilation a latency of less than 20 seconds antecedes the onset of postasphyxial change. Within the span of a few seconds membrane potential recovers and overshoots the normal level. At a critical stage of repolarization motoneurons are capable of conducting impulses, but again lapse into block (Figs. 9, 10, 14, and 15). The newly established block is due to hyperpolarization and is anodal in type. It is a somatic rather than an axonal block. Final recovery from the postasphyxial block requires some 20 minutes. As soon as motoneurons perform the rapid transition from asphyxial block through normal to postasphyxial block they will, upon reasphyxiation, pass through a new and complete asphyxial cycle with the one difference that a marked phase of incrementing response is experienced due to asphyxial mitigation of the postasphyxial block (Fig. 14). Barbiturate narcosis depresses the response of dendrites in a manner that resembles anodal depression for it is relieved rather than reinforced by asphyxial depolarization (Fig. 15). Asphyxial augmentation of response may acquire spectacular dimensions when written upon a state of barbiturate depression. Blocking time of the spinal motoneurons is on the average about 3.5 minutes. It may be shortened by prior asphyxiation (Fig. 14) and is lengthened by cooling of the preparation. Narcotization has not been observed to alter survival time significantly (Fig. 15).     

Changes in late components of somatosensory evoked potentials in humans during repetitive stimulation

Human evoked potentials to somatosensory stimuli of non-painful and painful intensity recorded from the vertex have been studied. The indices of variability of N150 and P250 components registered in the same subject as well as indices of interrelationship between spontaneous changes of these components decreased when stimulus intensity increased. A supposition is advanced that the role of general source responsible for generations N150 and P250 components diminished when stimulus intensity increased, accordingly participation of autonomic sources became more prominent.     

Altered mechanical responses of malignant hyperthermic skeletal muscle during repetitive stimulation.

This investigation examined the mechanical responses of malignant hyperthermic (MH) and normal porcine skeletal muscle to repetitive stimulation. Twitch and maximal tetanic tensions were not significantly different between muscle types. Tensions produced during stimulation at 20-80 Hz were significantly less in MH muscle than in normal muscle. In addition, MH muscle showed significantly greater force decline (tetanic fade) at the end of contractions evoked by 20-80 Hz stimulation. When stimulated to fatigue, both normal and MH muscle exhibited similar rates of tension decline during the initial minutes. Further stimulation caused additional decline in normal muscle, but a tension plateau in MH muscle. In all cases, normal muscle had greater magnitudes of fatigue than did MH muscle. Results show that there are marked differences between MH and normal muscle in the mechanical responses to repetitive stimulation. Due to its inability to properly regulate intracellular Ca2+ exchange, it is possible that MH muscle might be a useful tool for identifying the mechanisms of muscle fatigue in normal muscle.     

Generators of synchronous activity of the locus coeruleus during development

The locus coeruleus is thought to play an important role in the development of the central nervous system through a coordinated release of noradrenaline. The influence of the locus coeruleus on its diverse targets is strongly synchronized by the existence of electrical and chemical coupling between neurones, afferent supply of the nucleus from restricted sources and diffuse innervation of target areas. Extensive coupling between neonatal locus coeruleus neurones produces rhythmic synchronized electrical activity and distributes afferent synaptic activity throughout the entire nucleus. The strength of electrical coupling declines with age but appears to persist to a limited extent in the adult.     

Endogenous adenosine involved in the mediation of spinal antinociception produced by stimulating locus coeruleus.

The focus of this study was to investigate whether spinal adenosine is involved in mediating descending nociceptive modulation by the locus coeruleus (LC). Nociceptive evoked responses in parafascicular (PF) neurons were studied before and after electrical stimulation of the LC as well as before and after intrathecal (i.t.) administration of phentolamine (Ph) or aminophylline (Aph), an adenosine receptor antagonist, and 5'ethylcarboxamidoadenosine (NECA), an adenosine agonist. The main results were as follows: (1) the nociceptive evoked responses recorded in PF neurons were suppressed by LC stimulation; (2) pretreatment with i.t., Ph (40 nmol) reversed the LC effects, i.e., the suppressive effect of LC stimulation on the PF nociceptive evoked responses was reversed in the presence of Ph; (3) smaller doses of i.t. Aph (120 nmol) blocked only the suppressive effect produced by LC stimulation, while larger doses (240 nmol) reversed the LC stimulation, i.e., the LC stimulation exerted a facilatatory effect; and (4) i.t. application of NECA, an adenosine agonist, suppressed the nociceptive discharges in PF neurons. The results suggest that spinal adenosine may be involved in the mediation of the spinal antinociceptive effect produced by LC stimulation.