Inhibitory effect of dopamine on the transmission of excitation in isolated rat spinal cord

The effects of dopamine on ventral root potential produced by a single supramaximal dorsal root stimulation of the dorsal root was investigated during experiments on isolated superfused spinal cord segments from 10–16-day old rats. A reciprocal dose-dependent inhibition of the mono- and polysynaptic components of reflex response was also observed. Minimum effective concentration was 1×10^–8 M dopamine. Extent of reflex response increased in step with dopamine concentration, so that the amplitude of the monosynaptic component of ventral root potential was decreased by 20% and 87% of baseline level by the action of 10^–4 and 10^–3 M dopamine respectively on the cord. The amplitude of the polysynaptic component was thereby decreased by an average of 18% and 87%. Findings indicate that dopaminergic brainstem-spinal pathways contribute to the governing of impulse transmission in the segmental reflex arcs. Inhibition of dopaminergic synaptic transmission probably underlies the increase in latency already described in the literature, as well as the increase observed in the threshold of reflex motor response to nociceptive action following either stimulation of the dopaminergic brainstem structures or intravenous administration of dopamine agonists.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 616–621, September–October, 1986.     

Depolarizing effects of dopamine on the primary afferent fibers of a segment isolated from the spinal cord of newborn rats

Effects of dopamine on dorsal root potentials were investigated during experiments on a segment of spinal cord isolated from 12- to 18-day-old rats. Applying dopamine to the brain was found to produce a slow, reversible, dose-dependent depolarization at primary afferent fiber terminals. This dopamine-induced depolarization was retained during complete blockade of synaptic transmission brought about by exchanging calcium ions in the perfusing fluid by magnesium or manganese ions. Minimum dopamine concentration required to produce this effect was 1·10^–10–1·10^–9 M. Peak amplitude of depolarization equaled 1.5 mV. Duration of this reaction ranged from 5.5 to 36.7 min, depending on the duration and concentration of dopamine application. Depolarizing response to dopamine differed considerably from GABA-induced dorsal root depolarization in amplitude and rate of rise. Haloperidol, a dopamine antagonist, reduced dopamine-induced dorsal root depolarization. Findings indicate that dopamine acts directly on the membrane of primary afferent fiber terminals, shifting membrane potential toward depolarization. This raises the possibility that dopaminergic brainstem-spinal pathways may exert an effect on sensory information transmission in segmental reflex arcs already traveling to the spinal cord.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 741–748, November–December, 1987.     

Evoked activity of spinal neurons in the early period after sciatic nerve division

The character of dorsal horn motoneurons and interneurons evoked by stimulation of the dorsal root, and activity of Renshaw cells in response to stimulation of the ventral root were studied in albino rats in the lower lumbar segments of the spinal cord 5 days after sciatic nerve division. A significant increase in the mean amplitude of excitatory postsynaptic potentials of motoneurons was observed on the side of division of the nerve. No significant change in membrane potential and in the threshold of appearance of the action potential of these motoneurons took place. The mean number of action potentials and the duration of discharge of the Renshaw cells and dorsal horn interneurons likewise were not significantly changed.Dnepropetrovsk Medical Institute, Ukrainian Ministry of Health. Translated from Neirofiziologiya, Vol. 24, No. 3, pp. 306–314, May–June, 1992.     

Retuning of segmental responses to peripheral stimulation in cats during fictitious locomotion

Segmental responses of the lumbosacral region of the spinal cord to peripheral afferent stimulation were studied in decorticated, immobilized cats before and during fictitious locomotion. The appearance of fictitious locomotion was accompanied by a tonic increase in the N₁-component of the dorsal cord potential and dorsal root potential. Against the background of this tonic increase, modulation of these responses depending on the phase of fictitious locomotion was observed. When the N₁-component and dorsal root potential were evoked at the end of the "extension" phase and at the beginning of the "flexion" phase their amplitude was greater, but when they were evoked at the end of the "flexion" phase and the beginning of the "extension" phase it was smaller. Polysynaptic and monosynaptic reflex response of motoneurons exhibited the same phase dependence during fictitious locomotion. The mechanisms and physiological importance of this retuning of segmental responses are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 3, pp. 283–291, May–June, 1981.     

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.     

Phase-dependent changes in dorsal root potential during actual locomotion in rats

Fluctuations in dorsal root potential (DRP) were investigated in trials on white rats during two types of locomotion, differing in the intensity of afferent flow (swimming and walking). Two negative waves of DRP were observed corresponding to the stance (or propulsive) phase and the swing (or transfer) phase within a single locomotor cycle. Whereas DRP had risen primarily during the stroke phase with increased intensity during swimming, it increased during the standing phase in walking. A relationship was revealed between the amplitude of DRP and the intensity of afferent flow apparent during passive displacement of the limb, as well as locomotion. It is concluded that DRP waves are mainly due to influences from peripheral afferents during actual locomotion.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 3, pp. 333–340, May–June, 1988.     

Depolarization of different groups of lumbar afferent terminals during fictitious scratching

The kinetics of primary afferent depolarization (PAD) in the lumbar spinal cord was studied in immobilized decerebrate and decapitated cats during fictitious scratching. Fictitious scratching was accompanied by tonic and periodic PAD. Periodic PAD was cophased in different segments of the lumbosacral enlargement. Tonic depolarization was observed in terminals of all groups of afferent fibers studied (low-threshold cutaneous and of groups Ia and Ib). Periodic changes were observed only in endings of low-threshold cutaneous fibers and group Ib fibers. The physiological role of modulation of PAD by the spinal scratch generator is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 569–577, November–December, 1979.     

Cholinergic modulation of the synaptic transmission in the frog spinal cord

It was found during experiments on isolated frog spinal cord involving extracellular recording from the dorsal roots (sucrose bridging) and intracellular recording from motoneurons by microelectrodes that 10 mM of the M-cholinomimetic arecoline produces motoneuronal depolarization which is matched by depolarizing electronic ventral root potentials and a rise in motoneuronal input resistance. Arecoline changes synaptic transmission by increasing the amplitude of postsynaptic potentials during intracellular recording and that of motoneuronal reflex discharges in the ventral roots but reduces the duration of dorsal root potentials. In the presence of arecoline, L-glutamate-induced motoneuronal response increases. Facilitation of synaptic transmission produced by arecoline in the spinal cord is bound up with cholinergic M₂- activation, since it is suppressed by atropine but not by low concentrations of pirenzipine; it is also coupled with a reduction in adenylcyclase activity. When motoneuronal postsynaptic response has been suppressed, as in the case of surplus calcium or theophylline, arecoline produces an inhibitory effect on the amplitude of motoneuronal monosynaptic reflex discharges which is suppressed by pirenzipine at a concentration of 1×10^–7 M. This would indicate the presence at the primary afferent terminals of presynaptic cholinergic M₁ receptors which mediate its inhibition of impulses of transmitter release. This effect is independent of changes in cyclic nucleotide concentration.A. M. Gorkii Medical Institute, Donetsk. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 399–405, May–June, 1987.     

Effects of vasopressin and oxytocin on dorsal root potentials in perfused spinal cord isolated from newborn rats

Dorsal root potentials before and after adding vasopressin or oxytocin to the perfusing fluid were investigated during experiments on one or two perfused spinal cord segments isolated from 12- to 16-day-old rats. It was found that both neuropeptides reversibly inhibited the amplitude of dorsal root potentials produced by stimulating the adjoining dorsal root. The effect was dependent on concentration and time of peptide action on the brain. Both vasopressin and oxytocin were found to produce slow, reversible, dose-dependent depolarization at primary afferent fiber terminals. Depolarization persists when trans-synaptic transmission has been completely blocked owing to substitution of calcium by manganese ions in the perfusing solution. Synaptic contacts are thought to exist between peptidergic hypothalamospinal fibers and dorsal root afferent fiber terminals. The functional significance of these connections is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 6, pp. 757–763, November–December, 1988.     

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.     

Limb movement,intensity of integral afferent impulses from limb receptors,and level of primary afferent terminal polarization during locomotion in cats decerebrated at high level

The relationship between parameters of electrical muscle activity, changes at hindlimb joint angles, intensity of integral afferent flow, and dorsal root potential during real-life locomotion was investigated in cats decerebrated at high level. Characteristics of rear limb movements before and after deafferentation were described. It was found that afferent activity during locomotion motion consists, of two components — a tonic and a periodic phasic stage. Three main waves may be distinguished in the latter, each of which gives rise to associated changes in the level of primary afferent terminal polarization. These changes in turn are summated with the effects produced by the central generator. Correlations, between the parameters of these processes were investigated and the mechanisms underlying afferent control of locomotion generator function discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 119–127, January–February, 1988.     

Depolarizing effects of dopamine on motoneurons from a segment of spinal cord isolated from newborn rats

The effects on dorsal root potentials of applying dopamine to the perfusing fluid were investigated in experiments on a segment isolated from the spinal cord of 13- to 18-day-old rats. Dopamine induced slow, dose-dependent depolarization in motoneurons in 28 trials out of 32, retained in the solution blocking synaptic transmission. Threshold concentration of dopamine in the normal perfusing fluid measured 1·10^–6 M and 1·10^–5 M in a calcium-free perfusate containing magnesium or manganese ions. Depolarization was accompanied by an increased rate of motor discharges recorded from the ventral root. Segmental reflex response produced by dorsal root stimulation was depressed following depolarization. Hyperpolarization in response to dopamine was observed in 4 out of 32 experiments. Dopamine-induced electrotonic dorsal root potentials were suppressed by prior haloperidol application to the brain.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 735–741, November–December, 1987.     

Responses of auditory medullary units to sinusoidally amplitude-modulated tones in frogs

Spike discharges of medullary units ofRana ridibunda in response to tones of optimal frequency for the neuron, with sinusoidal amplitude modulation, was studied. Reproduction of sound modulation in unit activity was assessed by the use of phase histograms of responses corresponding to the period of modulation. Amplitude modulation was reproduced in the firing pattern of neurons of the dorsal nucleus over a wide range of modulation frequencies and carrier levels. Accentuation of small changes of amplitude for modulation frequencies of 70–150 Hz was observed in many neurons of the superior olives. The phase of the response was a linear function of modulation frequency both in the dorsal nucleus and in the superior olives. The greatest enhancement of amplitude changes corresponded to low modulation indices.Academician N. N. Andreev Acoustics Institute, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 390–396, May–June, 1985.     

Effects of vasopressin and oxytocin on evoked dorsal horn cell activity in an isolated segment of spinal cord

During experiments on an isolated segment of the spinal cord of 2- to 3-week-old rats, a study was made of the effects of vasopressin and oxytocin on the activity of dorsal horn cells produced by stimulating the afferent root. Both field and action potentials were recorded in single cells. It was established that vasopressin and oxytocin produced reversible inhibition of the postsynaptic component of field potentials. The amplitude of potentials was reduced by 33–39% by vasopressin and by 12–34% using oxytocin. The effect of the test substances depended on the concentration used and the duration of their action on the brain. Both vasopressin and oxytocin reversibly depressed discharges of single dorsal horn cells evoked by stimulating the dorsal root. These two neuropeptides prolonged latency, and reduced the number of evoked potentials or completely suppressed response. A facilitatory effect was recorded in a small number of cells. We deduced from our findings that their hypothalamospinal neurohormonal system inhibits transmission of afferent impulses at the level of interneurons of the dorsal horn.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 634–640, September–October, 1985.     

Effects of tractotomy on reflex activity in the lumbar segment of the rat spinal cord previously disrupted by severing the sciatic nerve

Evoked electrical discharges in the spinal cord roots and dorsal surface ipsilateral to the previously severed sciatic nerve (as well as on the contralateral side) were investigated in rats one, three, seven, and 14 days after tractotomy. Monosynaptic reflex discharges in the ventral roots were found to return to 20–40% of the level of this parameter as measured on the contralateral side within seven and 14 days after tractotomy. Mean amplitude of antidromic dorsal root discharges, afferent peak, and the N₁ component of potential(s) at the dorsal surface ipsilateral to the severed nerve barely altered, remaining significantly lower than on the contralateral side. Mechanisms are suggested for the increase in monosynaptic reflex ventral root discharges ipsilateral to the severed nerve following tractotomy — thought to be largely due to raised sensitivity to transmitter at the motoneuronal membrane resulting from degeneration of synapses of descending pathways.Medical Institute of the Ukrainian Ministry of Health, Dnepropetrovsk. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 366–371, May–June, 1989.     

Influence of the stimulation of the dorsal hippocampus on the dorsal root potentials of the spinal cord in the cat

Rhythmic stimulation of the dorsal hippocampus causes a long-lasting (2–6 sec) depression of both the fast and the electrotonic dorsal root potentials. The depression depends on the intensity of the stimulation of the hippocampus and on the time interval between the stimulation of the hippocampus and the nerve. The sortest time interval producing the depression was within 15–20 msec. The action of afferent impulsation is depressed during both the ipsilateral and contralateral stimulation of the hippocampus. The stimulation of the fornix also exerts a depressing influence on the dorsal root potentials; however, it is not so prolonged as the stimulation of the hippocampus (500–600 msec).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 186–193, September–October, 1969.     

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.     

Dopamine and serotonin effects on neurons of dorsal root ganglion isolated from rats

The effects of 1×10^–8–1×10^–5 M dopamine (DA) and serotonin (HT) on membrane potential, input resistance (R_M), and action potential (AP) when added to the superfusing fluid for 0.5 min were investigated in perfused dorsal root ganglia (DRG) neurons isolated from 30–36-day old rats during experiments using intracellular recording techniques. Application of DA induced reversible changes in membrane potential in 48 out of 52 test cells as compared with 38 out of 44 for HT. Distribution of different patterns of response to DA and HT was similar: depolarization was recorded in 64.6 and 73.7% and hyperpolarization in 16.7 and 15.8%; two-stage response occurred in 18.7 and 10.5% of responding cells, respectively. Both monoamines induced reversible change in the AP and R_M pattern in a number of cells. Depolarization was accompanied by a decline and hyperpolarization by a rise in R_M. Both substances were found to affect mainly those neurons with electrophysiological properties characteristic of small cells. The possibility of afferent spike train modulation at the level of primary sensory neurons is suggested.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian USSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 644–651, September–October, 1989.     

Effects of dopamine on background and evoked activity in interneurons of a spinal cord segment isolated from infant rats

The effects of 1·10^–5–1·10^–3 M dopamine on background and evoked interneuronal-activity was investigated during experiments on a spinal cord segment isolated from 11–18-day old infnat rats. Dopamine induced an increase in background firing activity rate in 52.5% and a reduced rate in 42.5% of the total sample of responding cells. Dopamine exerted a primarily inhibitory effect on interneuronal activity invoked by dorsal root stimulation, as witnessed by the reduced amplitude of the postsynaptic component of field potentials in the dorsal horn together with the fact that invoked activity was depressed in 66.7% of total interneurons responding to dopamine and facilitated in only 33.3% of these cells. All dopamine-induced effects were reversible and dose-dependent. Dopamine-induced effects disappeared after superfusing the brain with a solution containing 0–0.1 mM Ca²⁺ and 2 mM Mn²⁺, suggesting that this response is of transsynaptic origin. In other cells the excitatory or inhibitory action of dopamine also persisted in a medium blocking synaptic transmission; this would indicate the possibility of dopamine exerting depolarizing and hyperpolarizing effects on the interneuron membrane directly. Contrasting responses to dopamine in interneurons may be attributed to the presence of different types of dopamine receptors in the spinal cord.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 7–16, January–February, 1989.     

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

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