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.     

Neuronal organization of coeruleo-spinal connections in cats

Experiments on cats showed that electrical stimulation of the locus coeruleus leads to diminution of the inhibitory action of flexor reflex afferents (FRA) on the extensor monosynaptic reflex and to a decrease in amplitude of the IPSP evoked by FRA in extensor motoneurons. Injection of microdoses of aspartic acid and chlorpromazine into the locus coeruleus depresses the inhibitory effects of FRA, whereas injections of procaine and noradrenalin potentiate the inhibitory action of FRA. Data are given on the character of the descending influence of the locus coeruleus on different groups of spinal interneurons. It is concluded that depression of the inhibitory action of FRA is effected at the level of the final inhibitory interneurons of the "FRA system."A. A. Bogolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 362–374, May–June, 1984.     

Changes in postsynaptic responses in spinal motoneurons during repetitive stimulation of the locus coeruleus

Experiments on cats anesthetized with chloralose showed that repetitive stimulation of the locus coeruleus is accompanied by a decrease in IPSPs evoked by stimulation of flexor reflex afferents in extensor motoneurons. The effect appeared 600 msec after the beginning of stimulation and reached its maximum after 1500–2000 msec. Repetitive stimulation of the locus coeruleus did not change the membrane potential and did not affect EPSPs or IPSPs evoked by stimulation of low-threshold muscle afferents; EPSPs due to activation of high-threshold cutaneous and muscle afferents likewise remained unchanged. Repetitive stimulation of more central regions of the brain stem was accompanied not only by a decrease in IPSPs evoked by stimulation of flexor reflex afferents in extensor motoneurons, but also by a decrease in amplitude of EPSPs arising in response to stimulation of these same afferents in flexor motoneurons. These effects were not connected with activation of monoaminergic structures, for unlike effects arising during stimulation of the locus coeruleus, they were also found in previously reserpinized animals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 1, pp. 51–59, January–February, 1982.     

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.     

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.     

Late long-lasting discharges in hind limb motor nerves and their connection with the locomotor rhythm in thalamic immobilized cats

Effects of stimulation of flexor reflex afferents were studied in decerebrate immobilized cats. Stimulation of ipsilateral afferents evoked late long-lasting discharges in the nerves to the flexors, whereas stimulation of contralateral afferents led to similar discharges in nerves to both extensors and flexors. Compared with spinal animals, early segmental reflexes in thalamic cats were tonically depressed. Similar tonic inhibition of segmental reflexes took place in spinal animals after injection of dopa. Segmental reflexes were clearly modulated during late or rhythmic discharges. The possible central mechanisms of these changes in the segmental reflexes are discussed on the basis of data in the literature.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 2, pp. 137–145, March–April, 1979.     

Segmental inhibitory response in the frog spinal cord during orthodromic motoneuron activation

Different types of reflex discharges were produced in various preparations by stimulating the dorsal root of isolated frog spinal cord. These ranged from multiphasic low-amplitude waves to distinctly synchronized monosynaptic response. The discharges were followed by facilitation in the former and deep, protracted inhibition of response to test dorsal root stimulation in the latter. When interstimulus intervals measured 40–50 msec, inhibitory action was less pronounced than at shorter (15–30 msec) or longer (60–100 msec) intervals, thus indicating that at least two types of inhibition were at work, one at an earlier and the other at a later stage. Strychnine at a concentration of 10^–5 M effectively reinforced the former and blocked the latter, while 10^–4 M d-tubocurarine attenuated both types of inhibition substantially. It is concluded that inhibition of response occurs mainly as a result of recurrent activation of inhibitory systems via recurrent motoneuron axon collaterals when frog spinal cord afferents are excited. Intensity of the later (presynaptic) and earlier (postsynaptic) inhibition of reflex transmission is determined by the degree of synchrony in motoneuronal discharge in response to orthodromic stimulation.Institute of Medical Radiology, Academy of Medical Sciences of the USSR, Obninsk, Kaluga Oblast. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 343–350, May–June, 1987.     

Altered excitability of and synaptic effects of motoneurons during the establishing of a locomotor generation in the cat

Research was performed on spinal cats injected with DOPA and decorticate (decerebrated at level A 13) and spinal cats. It was found that formation (activation) of the spinal locomotor generator is accompanied by heightened excitability in the extensor and the reverse trend in the flexor motoneurons, by an increase in the efficacy of recurrent and reciprocal Ia inhibition of -motoneurons, and by a weakening of the influence of Ib afferents and extensor reflex afferents on these same motoneurons. The likely functional role of these changes in tuning of the spinal segmental apparatus in the generation of locomotor rhythm is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 679–687, September–October, 1986.     

Coerulospinal enhancement of repetitive firing with correlative changes in postspike afterhyperpolarization of cat spinal motoneurons

The present study was aimed at determining if inputs from the locus coeruleus (LC) have any effect on repetitive firing of ventral horn motoneurons in cats. In hindlimb flexor and extensor motoneurons stimulated intrasomatically with current below the threshold for repetitive discharges, added LC-evoked excitatory post-synaptic potentials (EPSPs) were consistently found to produce repetitive firing, suggesting a lowering in the repetitive firing threshold attributable to excitatory LC inputs. With those extensor motoneurons showing episodic, self-sustained firing, LC-EPSPs introduced during the quiescent period were capable of starting a continuous discharge with rhythmic frequencies higher than the spontaneous activity. In some of these cells, intracellularly applied hyperpolarizing current was able to stop the spontaneous discharges. Subsequently, LC stimuli were found to reinitiate repetitive discharges, thus counteracting the ongoing suppression of the motoneurons. Quantitative analysis of the single-spike afterhyperpolarization (AHP) indicated a consistent reduction in its amplitude and time course (duration, time-to-peak, half-decay time) for flexor and extensor motoneurons in response to LC conditioning stimuli. Present results suggest an excitatory LC action on the repetitive discharges of cat motoneurons accompanied by a concurrent decrease in the amplitude and time course of the single-spike AHPs.     

Convergence of synaptic influences of contralateral somatic afferents on interneurons in segmental inhibitory pathways to motoneurons

Convergence of contralateral somatic afferent synaptic influences on segmental inhibitory neurons was investigated by intracellular recording of postsynaptic potentials of -motoneurons in experiments on cats. Excitatory synaptic influences of afferents of the contralateral flexor reflex were shown to converge on interneurons of both segmental inhibitory systems studied: afferents of flexor reflex and group Ia muscle afferents. Interneurons of inhibitory systems are exposed not only to excitatory but also to inhibitory contralateral influences. Contralateral inhibitory PSPs of montoneurons are produced through ipsilateral inhibitory systems; a leading role is played by inhibitory neurons of the flexor reflex system of afferents. Inhibitory neurons of the Ia system as a rule do not make an important contribution to generation of contralateral IPSPs.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 5, pp. 476–484, September–October, 1973.     

Reflex mechanisms of fore-hindlimb relations demonstrable in lumbar flexor centers of the cat spinal cord

The dynamics of interaction between segmental, propriospinal, and spino-bulbo-spinal components of reflex responses of lumbar flexor centers was investigated during activation of forelimb and hindlimb afferents in cats. The monosynaptic flexor reflex to activation of hindlimb afferents is facilitated up to 300% when it coincides in time with the reflex discharge evoked by activation of forelimb afferents, and it remains increased up to 120–140% for 40–50 msec during the aftereffect of such activation. Polysynaptic flexor reflexes of segmental, propriospinal, and spino-bulbo-spinal origin have both facilitatory and inhibitory effects on each other. Facilitation is observed only while the interacting responses coincide in time, inhibition when they do not coincide. Three type of inhibitory effects with durations of 7–15, 40–150, and 300–500 msec are observed. The possible neuronal mechanisms of interaction between these reflexes and their role in functional relations between the fore- and hindlimbs are discussed.     

Pyramidal influences on interneurons of spinal segmentary reflector arcs in cat

Microelectrode discharges of potentials have been realized from segmentary interneurons of the dorsal horn and intermediate nucleus of the spinal cord in cat at the L₆–L₇ level by electrical stimulation of the sensorimotor region of the brain cortex. It has been established that corticifugal influences on segmentary interneurons of the system of the flexor reflex and on neurons activated by high threshold muscle afferents (groups Ib, II, and III), or high threshold cutaneous afferents are predominantly excitatory. Interneurons activated by muscle afferents of group Ia or by the lowest threshold cutaneous fibers are weakly subjected to pyramidal influences. The mean latencies of excitatory postsynaptic potentials (EPSP's) and discharges evoked under the influence of pyramidal volley, for the neurons under study in the system of afferents of the flexor reflex are equal to 11.8±2.6 and 20.1±1.8 msec, respectively; for interneurons, excited only by high threshold muscle afferents, they are equal to 15.5±3.6 and 16.3±2.2 msec, respectively; and for interneurons, excited by high threshold cutaneous fibers they are equal to 11.8±2.6 and 18.3±1.4 msec, respectively. Possible pathways of activating segmentary interneurons from the lateral sensorimotor region of the brain cortex have been discussed.The A. A. Bogomolets Institute of Physiology, Academy of Sciences, Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 17–25, January–February, 1970.     

Influence of forelimb afferents on the activity of lumbar spinal-cord motoneurons

Experiments were conducted on anesthetized cats with microelectrode recording to study the synaptic responses that develop in the lumbar motoneurons on stimulation of the afferent fibers of groups II and III in the nerves of the ipsilateral and contralateral forelegs. Stimulation of these afferents evoked predominantly inhibitory postsynaptic potentials (IPSP) in the extensor motoneurons and excitatory postsynaptic potentials (EPSP) in the flexor motoneurons. A basically inhibitory change in the rhythmic background activity developed under the influence of descending impulsation. The duration of the total inhibition of "spontaneous" motoneuron activity corresponded to the duration of the inhibitory influences exerted by the forelimb flexor-reflex afferents (FRA) on the interneurons. The interaction of the descending and segmental PSP resulted in inhibition and facilitation of the segmental responses in the motoneurons. The ultimate result of this interaction was determined by the shifts in the membrane potential of the motoneuron and by the effects created in the interneurons.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 58–67, January–February, 1971.     

Changes in the excitability of and synaptic effects on motoneurons during formation of the scratch motion generator in the cat

Studies on immobilized decerebrate (at intracollicular level) cats in which the scratch generator had been set up following bicuculline application to the upper cervical segments of the spinal cord, showed that the state of the segmental apparatus of the lumbosacral section of the spinal cord differs substantially from that seen in the spinal animal. Direct excitability of motoneurons of the "aiming" and "scratching" muscles rises, while recurrent and reciprocal Ia inhibition of motoneurons intensifies and the influence of Ib afferents on motoneurons declines. Afferents of the flexor reflex exert a primarily inhibitory influence on motoneurons of the "aiming" muscles. This influence becomes predominantly excitatory following spinalization, while the inhibitory effects of these afferents on motoneurons of the "scratch" muscles declines. The functional significance of the changes discovered in generation of scratch routine is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 2, pp. 244–250, March–April, 1987.     

Synaptic effects of contralateral somatic afferents on spinal motoneurons

Electrical activity of flexor and extensor alpha-motoneurons of the lumbar segments of cat's spinal cord as recorded intracellularly during electric stimulation of afferents of the contralateral posterior limb. Contralateral postsynaptic potentials (PSP) were shown to be evoked by activation of cutaneous and high-threshold muscle afferents. The high-threshold afferents of various muscle nerves participate to varying degrees in the generation of contralateral PSP. Contralateral inhibitory postsynaptic potentials (IPSP) were recorded in both flexor and extensor motoneurons along with contralateral excitatory postsynaptic potentials (EPSP). There are no fundamental differences in their distribution between flexor and extensor neurons. Inhibitory influences as a rule are predominant in both during the first 20 msec, and EPSP are predominant in the interval between 20 and 100 msec. The balance of excitatory and inhibitory pathway activity was found to be not as stable as that of the homolateral pathways.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 418–425, July–August, 1971.     

Inhibition of jaw opening reflexes by stimulation of the central gray matter and raphe nuclei in cats

The effect of stimulation of the mesencephalic central gray matter and raphe nuclei on jaw opening reflexes evoked by excitation of high-threshold (dental pulp) and low-threshold (A-alpha) fibers of the infraorbital nerve afferents was studied in cats anesthetized with chloralose and pentobarbital. The jaw opening reflex evoked by stimulation of the dental pulp was shown to be effectively suppressed by conditioning stimulation of the central gray matter and raphe nuclei. The reflex evoked by stimulation of low-threshold infraorbital nerve afferents also was depressed (but less deeply and for a shorter period than the reflex evoked by stimulation of the dental pulp) during stimulation of the raphe nuclei and caudal zone of the central gray matter, but was unchanged after stimulation of the points located in the rostral zone of the central gray matter. Application of single stimuli or bursts of five stimuli with a frequency of 100 Hz had no effect on the reflexes studied. Short-term stimulation with a burst of 10–20 stimuli with a following frequency of 200–400 Hz led to inhibition of the reflexes, which lasted 450–1000 msec. Long-term stimulation of the central gray matter and raphe nuclei for 30 sec with a frequency of 50 Hz caused inhibition of jaw opening reflexes evoked by stimulation of both high- and low-threshold afferents for 60 min. Impulses from the central gray matter and raphe nuclei thus have a mainly inhibitory action on the jaw opening reflex evoked by stimulation of high-threshold afferents, but they act less effectively on the reflex evoked by stimulation of low-thres-hold afferents. The duration of inhibition depends essentially on the parameters of stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 374–387, May–June, 1984.     

Hypothalamic influences on unit activity in the cat superior colliculus

Experiments on immobilized unanesthetized cats showed that hypothalamic stimulation effectively modified spontaneous unit activity and activity evoked by photic stimulation in the superior colliculus. Long-latency responses, often with a tonic type of formation, were predominant. Meanwhile, definite differences were found in the character of influences from different regions of the hypothalamus. Stimulation of the anterior hypothalamic region and lateral hypothalamus led more frequently to inhibition of spontaneous activity, often expressed as the development of initial inhibition, especially during stimulation of the lateral hypothalamus. Definite modulation of spontaneous activity of cyclic type also developed. Influences from these structures on activity evoked by photic stimulation were chiefly facilitatory and modulating in character. Stimulation of the ventromedial nucleus could produce inhibitory and facilitatory effects equally on activity of tectal neurons, with a tendency for the frequency of manifestation of facilitation to increase when a series of stimuli was used. The mechanisms of triggering and realization of hypothalamic influences on activity in the superior colliculus are discussed.Ivano-Frankovsk State Medical Institute, Ministry of Health of the Ukrainian SSR. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 560–568, November–December, 1979.     

Effect of noradrenalin and serotonin on synaptic transmission in the rat spinal cord

Experiments on superfused isolated spinal cord preparations from rats aged 8–13 days showed that noradrenal in and serotonin have only a weak effect on monosynaptic reflex discharges but a substantial effect on polysynaptic motoneuronal discharges: noradrenalin potentiates whereas serotonin inhibits them. Both amines inhibit dorsal root potentials evoked by stimulation of high-threshold afferents. Potentiation of polysynaptic motoneuronal discharges induced by noradrenalin is connected with hyperpolarization of high-threshold afferents due to inhibition of the function of neurons in the substantia gelatinosa, and with increased excitability of interneurons participating in the generation of motoneuronal discharges. Serotonin inhibits polysynaptic motoneuronal discharges through its direct depolarizing effect on terminals of high-threshold afferents and depression of interneuron activity responsible for these discharges. Adrenergic and serotonin receptors, mediating these effects of noradrenalin and serotonin, were subjected to pharmacologic analysis.A. M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 241–247, May–June, 1982.     

Transmission of descending activity evoked by prolonged stimulation of the pyramids and red nucleus by groups of spinal interneurons

Responses of two groups of spinal interneurons to prolonged stimulation of the medullary pyramids and the red nucleus by repetitive and random sequences of stimuli were investigated in cats anesthetized with pentobarbital. Interneurons specialized for transmission of descending, but not peripheral, effects were excited by impulses from both higher structures; the evoked activity was stable and stationary in character in response to stimulation within the range from 20–30 to 75–100/sec. The response of interneurons activated by flexor reflex afferents was more complex and, as a rule, it was not stationary. Prolonged pyramidal stimulation led to an increase in the mean spontaneous firing rate, while stimulation of the red nucleus inhibited spontaneous activity. Statistical analysis of the records of unit activity on the "Dnepr'-1" computer was used to study some possible mechanisms of the transformation of activity in the lateral descending systems by these groups of interneurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 6, pp. 644–653, November–December, 1973.     

Role of tonic motor units in flexor reflex evoked by impulsation from a focus of inflammation

The reactions of single motor units (MU) of the flexor muscles (musculus tibialis anterior and musculus biceps femoris) to tactile (light touch), nociceptive (strong compression), and electrical stimulation of the skin of the same extremity were investigated in unanesthetized spinal rats and cats. These reactions were compared with the reactions of the same MU to impulsation from a focus of inflammation evoked on the same extremity. It is shown that the smaller the motor units (judging by the amplitude of its action potential), the higher its sensitivity to exciting and the lower its sensitivity to inhibitory effects from the flexor reflex afferents (FRA), the longer its after-discharges and the more pronounced its capacity for prolonged discharges in response to prolonged stimulation of the FRA. These functional properties of the small MU are characteristic of the tonic motor neurons and the slow muscle fibers innervated by them. It is shown that prolonged impulsation from a focus of inflammation evokes the continuous activity of precisely these (tonic) MU. The activity of the large (phasic) MU ceases 2–3 min after injury which causes a focus of inflammation. Such selective activation of only some of the tonic MU is evidently due to the fact that the prolonged exciting synaptic effect of impulsation from the focus of inflammation causes accommodation of the phasic motor neurons.Institute of Normal and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 3, pp. 308–315, May–June 1971.