Inhibitory Effects Of Electrical Stimulation Research Articles

The inhibitory effect of sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive bladder reflexes in cats.

To investigate the inhibitory effects of electrical stimulation of sacral dorsal root ganglion (DRG) on bladder activity under non-nociceptive and nociceptive bladder conditions in cats. 12 cats were divided into non-nociceptive and nociceptive groups. Saline was used to distend the bladder and induce non-nociceptive bladder activity, while acetic acid (AA, 0.25%) was used to induce nociceptive bladder overactivity, S1 or S2 DRG stimulation was applied via a pair of hook electrodes placed in the right S1 and S2 DRG. In both non-nociceptive and nociceptive groups, stimulation at 3 and 5Hz significantly increased bladder capacity (BC) and no significantly different between the two frequencies. In non-nociceptive group, S1 DRG stimulation at 3Hz was as effective (increasing BC to 139.7±5.6 and 166.9±12.21% of control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 129.2±5.6 and 160.5±13.3% of control). In nociceptive group, AA reduced the BC to 62.6±11.7% of saline control. S1 DRG stimulation at 3Hz was also as effective (increasing BC to 54.9±5.5 and 61.9±6.0% of saline control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 58.3±3.7 and 65.6±3.7% of control). This study showed the effective inhibition on bladder activity under both non-nociceptive and nociceptive conditions, suggesting the possibility of sacral DRG stimulation to treatbladder overactivity.

Septal stimulation inhibits spinal cord dorsal horn neuronal activity

Deep brain stimulation (DBS) has been used for relieving chronic pain in patients that have been through other existing options. The septum has been one of the targets for such treatment. The purpose of this study was to determine the inhibitory effect of electrical stimulation in the medial septum diagonal band of broca (MSDB) on neuronal activity in the spinal cord of rats anesthetized with sodium pentobarbital. While unilaterally stimulating the MSDB, wide dynamic range neurons in the lumbar region of the spinal cord were recorded in response to graded mechanical stimulation of the hind paws (brush, pressure, and pinch). Stimulation was at 1, 5, 10, and 20V, at 100Hz, and 0.1ms duration. Significant bilateral reduction was observed in response to pressure (ipsilaterally: 0.90±0.05, 0.48±0.06*, 0.55±0.05*, 0.40±0.05*; and contralaterally: 0.70±0.06*, 0.59±0.08*, 0.75±0.05*, 0.49±0.07*) and pinch (ipsilaterally: 0.89±0.08, 0.46±0.05*, 0.54±0.04*, 0.50±0.05*; and contralaterally: 0.78±0.05, 0.61±0.07*, 0.64±0.04*, 0.53±0.06*). Data were expressed as a fraction of control. Significant changes were also found in responses to brush in certain groups (ipsilaterally: 1.08±0.08, 0.72±0.06*, 1.00±0.12, 0.65±0.06*; and contralaterally: 0.93±0.05, 0.77±0.07*, 0.98±0.05, 0.84±0.07). Further analysis suggested that 5V was adequate for achieving optimal inhibition. It is concluded that the MSDB can be used as alternative target for DBS in the treatment of pain.

Inhibitory effects of electrical stimulation on delivery in pregnant rats

Objective To study the efficacy of uterine electrical stimulation (ES) with various parameters in delaying delivery in term- and preterm-laboring animals. Study design Catheters and electrodes, as well as ES electrodes, were sutured onto the uterine horn in day-15 pregnant rats. ES with various durations/frequencies (five sets of parameters) was tested from gestation day 21 to determine its effects on uterine contractility. The best set of ES parameters was applied in term (day 21) and preterm (day 18—labor induced) animals to determine the effects of ES on delivery. Results (1) Significant reduction in uterine contractions (0.54 ± 0.11 vs. 0.86 ± 0.08 contractions per minute, P < 0.001) was noted with ES of only one of the five sets of parameters (set #5 with pulse train of 10 s on and 10 s off, 28 ms pulse width, frequency of 30 Hz and amplitude of 4 mA); (2) ES with parameter set 5 delayed delivery by 12.5 h ( P = 0.01) and reduced area under the curve of intrauterine pressure in mmHg s (311 ± 147.21 vs. 848.75 ± 350.38, P < 0.05) and AUC-electromyographic activity is area under rectified (i.e. absolute value) uterine EMG trace in mV s (145.25 ± 93.1 vs. 410 ± 182.46, P < 0.05) in the term rats; and (3) similar effects were noted with ES in preterm rats with a delay in delivery by 28 h ( P < 0.001), and a decrease in IUP–AUC (intrauterine pressure–area under curve) (101.5 ± 55.45 vs. 551 ± 269.06, P = 0.017) and EMG–AUC (64.25 ± 43.63 vs. 172.5 ± 62.91, P = 0.03). Conclusion ES of the uterus with appropriate parameters inhibits uterine contractions and delays delivery in both term and preterm rats.

S1855 Inhibitory Effects of Electrical Stimulation of Various Organs Along the Gut On Antral Motility in Dogs

S1855 Inhibitory Effects of Electrical Stimulation of Various Organs Along the Gut On Antral Motility in Dogs

Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy.

Epilepsy can be considered as a result of the imbalance of the excitatory and inhibitory processes. Therefore, the artificial enhancement of the activity of brain inhibitory mechanisms might lead to a beneficial therapeutic effect for intractable epilepsy patients. Studies of the inhibitory effects of electrical stimulation of the head of the caudate nucleus (HCN), cerebellar dentate nucleus (CDN), thalamic centromedian nucleus (CM), and neocortical and temporal lobe mesiobasal epileptic foci were performed on 150 patients with implanted intracerebral electrodes. Chronic brain stimulation with implanted neurostimulators was performed on 54 patients. Sixteen were followed up to 1.5 years (mean 1.2 years). The study demonstrated that 4-8 Hz HCN and 50-100 Hz CDN stimulation suppressed the subclinical epileptic discharges and reduced the frequency of generalized, complex partial, and secondary generalized seizures. CM stimulation (20-130 Hz) desynchronized the EEG and suppressed partial motor seizures. Direct subthreshold 1-3 Hz stimulation of the epileptic focus may suppress rhythmic afterdischarges (ADs). Seizures were eliminated for 26 of 54 patients (48%), worthwhile improvement was achieved for 23 of 54 patients (43%), and no improvement was observed in 5 of 54 patients (9%). The artificial increase of the activity of brain inhibitory system may suppress the activity of epileptic foci, and, in long run, stabilize this epileptic foci activity at a lower, perhaps normal, level. Therapeutic direct brain stimulation, therefore, might serve as a useful tool in the treatment of intractable and multifocal epilepsy, and might be combined with ablative surgical methods.

Inhibitory effects of electrical stimulation of ventrolateral orbital cortex on the rat jaw-opening reflex

In previous studies, we have shown that electrically or chemically evoked activation of the ventrolateral orbital cortex (VLO) depresses the rat tail-flick (TF) reflex, and this antinociceptive effect is mediated by the periaqueductal gray (PAG). The aim of the present study was to examine whether electrical stimulation of the VLO could inhibit the rat jaw-opening reflex (JOR), and to determine whether electrolytic lesions of the PAG could attenuate this VLO-evoked inhibition. Unilateral electrical stimulation of the VLO significantly depressed the JOR elicited by tooth pulp or facial skin stimuli, with a mean threshold of 30.5±2.3 μA ( n=22). Increasing stimulation intensities from 30 to 80 μA resulted in greater reduction of the dEMG amplitude from 22.9±5.0% to 69.7±3.7% of the baseline value ( P<0.01, n=22). The inhibitory effect appeared 50 ms after the beginning of VLO stimulation and lasted about 150 ms, as determined by varying the conditioning-test (C-T) time interval. Unilateral lateral or ventrolateral lesions of the PAG produced only a small attenuation of the VLO-evoked inhibition of the JOR, but bilateral lesions eliminated this inhibition. These findings suggest that the VLO plays an important role in modulation of orofacial nociceptive inputs, and provide further support for the hypothesis that the antinociceptive effect of VLO is mediated by PAG leading to activation of a brainstem descending inhibitory system and depression of nociceptive inputs at the trigeminal level. The role played by VLO in pain modulation is discussed in association with the proposed endogenous analgesic system consisting of medullary cord–Sm–VLO–PAG–medullary cord.

Inhibitory effects of electrical stimulation of thalamic nucleus submedius on the nociceptive responses of spinal dorsal horn neurons in the rat

The aim of the present study is to examine whether stimulation of the thalamic nucleus submedius (Sm) exerts an inhibitory influence on the long latency responses (C-responses) of the spinal cord dorsal horn neurons evoked by noxious cutaneous electrical stimulation, in an attempt to provide electrophysiological evidence for involvement of the Sm in modulation of nociception. Single unit extracellular recordings from the dorsal horn neurons were obtained with glass micropipettes in pentobarbital-anesthetized rats. A total of 71 nociceptive neurons, including 61 wide dynamic range (WDR) and 10 nociceptive specific (NS) neurons, were studied in 29 rats. Electrical stimulation of either ipsilateral or contralateral Sm markedly suppressed the C-responses in most (75%, 53 71 ) of these neurons, and facilitated the responses in only a few neurons. In general, the inhibitory effect was dependent on both the stimulus intensity and the length of stimulus train, and the stimulus threshold for the inhibition to be elicited was about 50 μA when a 300-ms train of 0.2-ms pulses at 200 Hz was used. The inhibitory effect outlasted the Sm stimulation about 500 ms. Inhibition of C-responses could also be produced by stimulation of the dorsal hypothalamic area (DA). On the other hand, stimulation of the structures in the medial thalamus surrounding Sm had no obvious influences on the C-responses of the dorsal horn neurons. The findings of this study provided further support for the hypothesis that Sm may be implicated in the descending modulation of nociception.

Contralateral acoustic stimulation induces a phase advance in evoked otoacoustic emissions in humans

In 28 normal-hearing human subjects, the medial olivocochlear efferent system was activated by contralateral acoustic stimulation which is able to mimic the inhibitory effects of electrical stimulation of the crossed olivocochlear bundle. A first experiment on 16 subjects demonstrated that a contralateral white noise of 35 dB SL was able to induce temporal changes on transiently evoked otoacoustic emissions in response to clicks of 63 dB SPL. These temporal changes consisted of an advance of click-evoked otoacoustic signals in 87% of cases and is referred to as phase-shift effect. The phase advance, quantified using two signal processing methods in both time and frequency domains, was found to be mainly associated with lower frequencies, with a maximal effect at 1.5 kHz and minimal effects around 3.5 and 4 kHz. In a second experiment, carried out on 12 subjects, a negative relationship was found to exist between the ipsilateral stimulation level (level of clicks ranging from 57 to 69 dB SPL) and the phase-shift effect (PSE). Specifically in the range of levels tested (25–45 dB SL), a linear relationship presenting no obvious saturation effect was observed between the contralateral level and the PSE. The PSE was examined in 6 additional subjects exhibiting pathological symptoms; 2 of 3 individuals, who had no contralateral stapedial reflexes unilaterally, showed the PSE whereas this response was reduced or absent in 3 other subjects in the ear with severed efferents associated with a vestibular neurotomy. The integrity of olivocochlear efferents was, therefore, necessary to obtain a full effect, but the absence of stapedial reflex did not prevent the effect from occurring.

Inhibitory effects of electrical stimulation of thalamic nucleus submedius area on the rat tail flick reflex

This study in lightly anesthetized rats found that unilateral electrical stimulation delivered to the ventral part of the thalamic nucleus submedius (Sm), the thalamic reuniens nucleus (Re) and the hypothalamic dorsal area (DA) markedly depressed the TF reflex, and this inhibitory effect increased following increasing stimulation intensity. Stimulation in the dorsal part of Sm did not produce any or only slight depression of the TF reflex. Furthermore, an ipsilateral electrolytic lesion of the ventrolateral orbital cortex (VLO) eliminated the unilateral Sm-evoked inhibition, but not the inhibition elicited by Re and DA and contralateral Sm stimulation. Finally, after bilateral electrolytic lesions of the ventrolateral periaqueductal gray (PAG) the DA and Re and contralateral Sm-evoked inhibitions were also eliminated. The results suggest that the Sm plays an important role in modulation of nociceptive inputs, and this role of Sm is mediated by the VLO and leads to activation of the PAG descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.

Etude des modifications temporelles des otoémissions acoustiques provoquées lors d'une stimulation acoustique controlatérale, chez l'humain normo-entendant

In 32 subjects, the medial olivo-cochlear efferent system was activated by a contralateral acoustic stimulation (CAS) which is able to mimic the inhibitory effects of electrical stimulation of the crossed olivo-cochlear bundle. A white noise CAS of 35dB SL induced temporal alterations in otocoustic emissions evoked by clicks of 63dB SPL, called phase shift effect (PSE). The PSE appeared as an advance of signals in 80% of cases and occurred after a latency of about 8ms. Two different signal processing methods (in time and frequency domains), showed that the phase shift was mainly located on lower frequencies with a maximum around 1.5kHz and a lack around 4kHz. When contralateral stimulation intensity was varying from 25 to 45 dB SPL, the PSE, increased linearly; the shape of the curve allowed to rule out a middle ear reflex. On the contrary, when ipsilateral stimulation intensity was varying from 57 to 69 dB SPL, the PSE decreased linearly, indicating that PSE originated in inner ear mechanisms. Lastly, a significant correlation had been evidenced between the amplitude of the suppressive (inhibitory) effect of CAS, and the amplitude of the phase shift effect, allowing one to suggest that both effects may have a common physiological origin

Two forms of inhibition of spinothalamic tract neurons produced by stimulation of the periaqueductal gray and the cerebral cortex

1. Recordings were made from the lumbosacral spinal cord in anesthetized macaque monkeys. The inhibitory effects of electrical stimulation of the periaqueductal gray (PAG) and the cerebral cortex or cerebral peduncle (CP) were tested and compared by recording 1) cord dorsum potentials evoked by stimulation of the sural nerve, 2) discharges recorded extracellularly, and 3) membrane potentials recorded intracellularly from spinothalamic tract (STT) neurons at rest (background activity) or in response to stimulation of the sural nerve. 2. Stimulation of the cortex or in the CP preferentially reduced the amplitude of the N1 and N2 waves of the cord dorsum potential evoked by stimulation of the sural nerve, without affecting the N3 wave. Stimulation of the PAG, on the other hand, reduced the amplitude of the N3 wave with little effect on the N1 and N2 waves. 3. The activity of 62 STT neurons was recorded extracellularly. Stimulation of the PAG or the cortex/CP inhibited nonpreferentially the responses of the neurons in the superficial laminae to all afferent inputs. On the other hand, stimulation of the PAG or the cortex/CP inhibited preferentially the responses of most STT neurons in deep layers of the dorsal horn to the small or large afferent input, respectively. 4. Thirty-five neurons were recorded intracellularly. The membrane potential of the neurons averaged -45.5 +/- 10.1 (SD) mV. All neurons were recorded in laminae III-VI; the neurons were of the wide-dynamic-range (WDR) type and had background activity. 5. The inhibitory effects of stimulation of the PAG were tested on all 35 neurons. In 32 of the neurons, stimulation of the PAG evoked a hyperpolarization. The background activity of the neurons was reduced (generally it completely ceased) by the hyperpolarization. In three neurons stimulation of the PAG did not evoke a hyperpolarization and the background activity of the neurons did not change. Nevertheless, the responses of these three neurons to afferent input were inhibited by stimulation in the PAG. 6. The inhibitory effects of stimulating the cortex and/or the CP were tested in 26 of the 35 neurons. Stimulation of the cortex and/or the CP evoked a hyperpolarization in all the neurons, although, in 10 of the 26 neurons, stimulation of the CP also evoked a depolarization. The hyperpolarization generally blocked the background activity of the neurons. 7. The effective stimuli in the PAG and the cortex/CP to evoke a hyperpolarization in STT neurons were short, high-frequency trains of pulses.(ABSTRACT TRUNCATED AT 400 WORDS)

Arborization of single axons of the spinal dorsolateral funiculus to the contralateral superficial dorsal horn

This study provides an anatomical basis for the observation that a unilateral lesion of the spinal dorsolateral funiculus (DLF) can reduce the inhibitory effect of electrical stimulation of the nucleus raphe magnus (NRM) on dorsal horn nociceptive neurons located caudal and contralateral to the lesion. We injected the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the NRM and traced the arborization of single DLF axons in the spinal gray matter. Although the majority of DLF axons arborized in the dorsal horn ipsilaterally, we found some axons which entered the spinal gray matter, traversed the gray matter to the central canal and then abruptly changed direction and coursed to the contralateral superficial dorsal horn. Very few branches were given off en route. These data indicate that some raphe-spinal axons may selectively influence the firing of neurons of the superficial dorsal horn, contralateral to the DLF in which they descend the spinal cord.

Brainstem and spinal pathways mediating descending inhibition from the medullary lateral reticular nucleus in the rat

The lateral reticular nucleus (LRN) in the caudal ventrolateral medulia has been implicated in descending monoaminergic modulation of spinal nociceptive transmission. Experiments were undertaken to examine the organization of pontine and spinal pathways mediating inhibition of the tail-flick (TF) reflex from the LRN in rats lightly anesthetized with pentobarbital. Microinjections of the local anesthetic lidocaine ipsilaterally or bilaterally into the dorsolateral pons blocked stimulation-produced inhibition of the TF reflex from the nucleus locus coeruleus/subcoeruleus (LC/SC), but had no effect on descending inhibiton produced by microinjection of glutamate into the LRN. Thus, adrenergic modulation of the TF reflex from the LRN is not mediated by activation of spinopetal noradrenergic neurons in the LC/SC. The funicular course of descending inhibition produced by focal electrical stimulation in the LRN was studied in separate groups of rats by reversibly (local anesthetic blocks) or irreversibly (surgical transection) compromising conduction in the dorsolateral funiculi (DLFs) at the level of the cervical spinal cord. Bilateral iidocaine blocks in the DLFs significantly shortened control TF latencies and more than doubled the intensity of electrical stimulation in the LRN necessary to inhibit the TF reflex (153 ± 29% increase from control); changes in these parameters produced by unilateral blocks of the DLFs were not statistically significant. Ipsilateral or bilateral transections of the DLFs significantly increased the intensity of electrical stimulation in the LRN to inhibit the TF reflex (110 ± 24% and 265 ± 46% from the control, respectively). Neither lidocaine blocks nor transection of the DLFs completely blocked the descending inhibitory effects of electrical stimulation in the LRN. The DLFs appear to carry fibers mediating LRN stimulation-produced inhibition of the TF reflex as well as tonic descending inhibition of spinal reflexes. The results of the present study indicate that (1) adrenergic modulation of the nociceptive TF reflex from the LRN does not depend on a rostral loop through the pontine LC/SC, and (2) descending inhibitory influences from the LRN are contained in, but not confined to, the dorsal quadrants of the spinal cord.

Inhibitory effect of electrical stimulation of raphe nucleus on growth hormone secretion in pentobarbital anesthetized rats

Inhibitory effect of electrical stimulation of raphe nucleus on growth hormone secretion in pentobarbital anesthetized rats

Vascular effects of free radicals generated by electrical stimulation

Electrical field stimulation (9 V, 1.0 ms, 4 Hz) of isolated segments of rat tail arteries and dog coronary arteries inhibits contractile responses to exogenous norepinephrine and elevated potassium concentration. This inhibitory effect of electrical stimulation is blocked by various agents that alter oxygen metabolism: superoxide dismutase, catalase, glutathione, ascorbate, and dimethyl sulfoxide. The observations suggest that the inhibitory effect is due to an action of oxygen free radical metabolites that are generated by the electrical stimulation of the oxygen-rich buffer. These free radical metabolites have two actions: 1) they oxidize drugs in the experimental system, and 2) they exert a direct inhibitory action on vascular smooth muscle.

Excitation and inhibition of cardiac vagal motoneurones by electrical stimulation of the carotid sinus nerve.

1. The carotid sinus nerve was electrically stimulated in dogs anaesthetized with chloralose. Stimuli (1 ms, 1-10 V, less than or equal to 1 Hz) evoked responses in single cardiac efferent fibres dissected from the cervical part of the vagus nerve. The mean latencies of these responses varied, from fibre to fibre, between 30 and 120 ms. 2. Stimuli given during the expiratory phase of the respiratory cycle evoked vagal responses with a shorter latency than similar stimuli given only during the inspiratory phase of the respiratory cycle. 3. Following the vagal response to carotid sinus nerve stimulation a period of inhibition of vagal activity, lasting 100-150 ms, occurred. Refractoriness of the responding vagal motoneurone following an action potential could not account for this post-excitatory depression. 4. The inhibitory effects of electrical stimulation of the carotid sinus nerve were further studied by applying pairs of similar electrical stimuli to the carotid sinus nerve. The second stimulus of a pair had to be given 80-100 ms after the first to evoke a second response. 5. Trains of electrical stimuli (30-100 Hz) were also studied. At low frequencies the inhibitory effect of successive stimuli on vagal responses became less marked, but at higher frequencies only the first and last stimulus of the train reliably evoked responses. For trains of stimuli at both low and high frequencies, the last stimulus of the train evoked a vagal response, which was succeeded by a period of inhibition of vagal firing: this inhibition was then followed by further excitation before vagal discharge returned to resting levels.

Differential inhibitory effects of medial and lateral midbrain stimulation on spinal neuronal discharges to noxious skin heating in the cat.

1. The inhibitory effects of electrical stimulation in midbrain periaqueductal gray (PAG) and lateral reticular formation (LRF) on spinal dorsal horn neuronal responses to noxious skin heating were investigated in cats anesthetized with Nembutal and N2O. 2. Thirty-one dorsal horn units driven by electrical stimulation of the posterior tibial and/or superficial peroneal nerves at A- and C-fiber strength responded to noxious radiant heating (e.g., 50 degrees C) of the skin of the hindpaw. All units tested were inhibited by electrical stimulation (100-Hz trains, 3/s) of both PAG and LRF. 3. Systematic tracking with the stimulating electrode revealed that descending inhibition is generated at sites throughout the mediolateral extent of the midbrain. Particularly effective sites were in LRF and PAG. 4. More powerful descending inhibition was generated from LRF than from PAG sites, based on quantitative comparison in the same unit of a) degree of inhibition of spinal unit heat-evoked discharges by PAG and LRF stimulation at the same current intensity, b) current threshold for inhibition by PAG and LRF stimulation, and c) slope of curves plotting degree of inhibition in relation to intensity of PAG and LRF stimulation. 5. Dorsal horn neurons show a linear relationship between response magnitude and temperature of skin heating during a series of heat stimuli (42-50 degrees C) applied at 3-min intervals. When the series is repeated during PAG stimulation, the slope of the linear temperature-response curve is reduced without a change in the response threshold. In contrast, repetition of the heating series during LRF stimulation produced a parallel rightward shift in the linear temperature-response curve, with commensurate increase in response threshold. 6. The results indicate that functionally separate descending inhibitory systems are activated by stimulation of PAG and LRF. Possible inhibitory mechanisms and the functional significance of descending inhibition from PAG and LRF are discussed.

The rubro-bulbospinal path. A descending system known to influence dynamic fusimotor neurones and its interaction with distal cutaneous afferents in the control of flexor reflex afferent pathways.

The inhibitory effect of electrical stimulation in the near-rubral region on polysynaptic segmental as well as ascending pathways activated by the flexor reflex afferents (FRA) in hind limb nerves was studied in chloralose anaesthetized cats. The effective stimulating region totally coincided with the one from which a D zone climbing fibre response may be elicited in the contralateral cerebellar cortex. The descending path was dependent upon an intact dorsolateral spinal funiculus, where also a characteristic volley could be recorded with a surface electrode on short train central stimulation. The suppressive action on the transmission through the FRA pathways was evoked in the absence of a lower lumbar dorsal root potential, and it was concluded that the effect was exerted by postsynaptic inhibition. It was suggested that this descending path, the effects of which resemble those elicited from the dorsal reticulospinal system, is identical to the rubro-bulbospinal path, previously known to influence dynamic fusimotor neurones. The transmission through the FRA pathways was also suppressed by conditioning stimulation of ipsilateral, low threshold distal cutaneous afferents. The time course of this effect was the same as that with central conditioning stimulation. Facilitatory interaction was revealed with double conditioning and it was suggested that the descending path and the distal cutaneous afferents converge upon a common group of interneurones, which postsynaptically inhibit an early (possibly the first one) interneurone in the FRA pathways. As low threshold distal cutaneous afferents supply the primary peripheral input via climbing fibres to the cerebello-cortical D zone, it was concluded that the different stimuli (central or peripheral) which activate a common group of inferior olivary neurones destined for the D zone also activate a common group of segmental inhibitory interneurones. The results are discussed in relation to current concepts of segmental motor control, and it is suggested that the mechanisms studied could be involved in the regulation of stepping.

The spinal route of sympatho-inhibitory pathways descending from the medulla oblongata.

1. The effect of making discrete lesions in the cervical spinal cord on the brainstem elicited inhibition of a spinal somato-sympathetic reflex response has been studied in anaesthetized cats. 2. Electrical stimulation within three areas of the medulla caused an inhibition of the spinal component of the reflex response elicited in thoracic white rami communicantes by stimulation of intercostal nerves. The three medullary areas studied were the ventrolateral medulla and the caudal rephe nucleus, from where bulbospinal monoamine neurones originate, and the ventromedial reticular formation. 3. The inhibitory effects of stimulation in the ventrolateral medulla and raphe nucleus were abolished by the destruction of parts of the ipsilateral dorsolateral funiculus of the cervical spinal cord, whereas the inhibition produced by ventromedial reticular formation stimulation was abolished by lesions which included part of the ventral quadrant of the cord. 4. The time course of the inhibitory effects of electrical stimulation of descending sympatho-inhibitory tracts in the cervical spinal cord was studied in unanaesthetized decerebrate cats spinalized at C1. Inhibition obtained from the dorsolateral funiculus characteristically had a longer time to onset than inhibition obtained from the ventrolateral and ventral funiculi.

(3H)-adenine nucleotide and (3H)-noradrenaline release evoked by electrical field stimulation, perivascular nerve stimulation and nicotine from the taenia of the guinea-pig caecum.

1. The release of [(3)H]-noradrenaline and adenine nucleotide evoked by electrical field stimulation (20-60 V, 30 Hz), perivascular nerve stimulation (20-80 V, 60 Hz) and nicotine (10, 100 muM) was studied in the taenia of the guinea-pig caecum under various conditions.2. Electrical stimulation at high intensity (60 V) caused the release of [(3)H]-adenine nucleotide; however, the inhibitory action of electrical stimulation was proportional to [(3)H]-noradrenaline release.3. The intensity of the inhibitory effect of stimulation of the perivascular nerves was directly related to [(3)H]-noradrenaline release and not associated with the release of [(3)H]-nucleotide.4. Cold storage for more than 8 days, cooling (19 degrees C) or tetrodotoxin treatment (1 mug/ml) abolished the inhibitory responses to electrical stimulation and to nicotine. After these treatments, nicotine and electrical stimulation elicited only contractions; the release of [(3)H]-noradrenaline, but not that of [(3)H]-adenine nucleotide, was inhibited.5. The dissociation of the inhibitory effects of electrical stimulation and nicotine from [(3)H]-nucleotide release does not support the hypothesis that ATP or a related nucleotide is the humoral transmitter of the non-adrenergic inhibition in the taenia of the guinea-pig caecum.