Transposition of the pacemaker in the right atrium during stimulation of the vagus nerve in the dog

The heart rate and intraatrial latencies between epicardial electrograms from three sites of the right atrium have been studied during vagal stimulation in open-chest dogs. It has been shown that alterations of latencies started at a certain cardiac cycle length irrespective of pacing frequency. A transitional process of changes from a steady latency value in the control to another steady value during vagal stimulation has been observed. The transitional process has been simulated in experimental procedure in which two sites of the right atrium were paced at close and constant frequencies. To interpret the results obtained one-dimensional model of the sinus node has been constructed. According to the model, pacemaker shift within the sinus node results from a competition between two foci of automaticity with close intrinsic frequencies.     

Maintained depressor responses evoked by continuous and intermittent stimulation of aortic nerve in the rabbit

Stability of depressor responses evoked by long-lasting continuous and intermittent stimulation of the aortic nerve was studied in rabbits anaesthetized with urethane. Continuous stimulation produces blood pressure falls whose stability at low frequencies (1-10 cycles/sec) ranges from 91 to 86%. With rise of the stimulation frequency stability is decreased : at 500 cycles/sec, it amounts to 19%. Intermittent stimulation consisting in switching excitation on and off every 10 sec increases stability of depressor responses and at 500 cycles/sec, it is significantly higher than stability of effects produced by continuous stimulation. Following transection of aortic nerves, stability is increased at all frequencies of continuous stimulation and at all but the lowest frequency of intermittent stimulation. Vagotomy performed after section of the aortic nerves does not significantly affect the changes in stability observed after severing the aortic afferents. It is suggested that at high frequencies of stimulation, stability of depressor responses is reduced by homosynaptic depression. During intermittent stimulation, its effect is counteracted by post-tetanic changes occurring at intervals when the stimulation is switched off. The increase in stability after section of aortic nerves is probably related to its effect on excitability of the vasomotor centres.     

Influence of superior cervical ganglion stimulation frequency on salivary secretion in the rabbit. Comparative study of parotid and mandibular glands

Saliva secretion in response to the stimulation of the superior cervical ganglion (S.C.G.) at different frequencies (2, 3, 5, 10, 15, 20 Hz) has been studied in anaesthetized rabbits. The differences between the two major glands in this species were analyzed, with respect to the flow response, potassium, amylase and total protein content during the sympathetic stimulation. The stimulation of S.C.G. increased the salivary flow rate at all frequencies, on both parotid and mandibular gland. In the parotid gland the flow and stimulation frequency show a positive linear correlation which does not appear in the mandibular gland. In conclusion, the differences observed in the response to sympathetic stimulation in both glands seem to be due to distinct patterns of sympathetic innervation on different glandular elements.     

Study of the frequency parameters of EEG influenced by zone-dependent local ELF-MF exposure on the human head

It has been reported that human subjects exposed to electromagnetic fields exhibit changes in human EEG signals at the frequency of stimulation. The aim of the present study was to expose different parts of the brain to extremely low-frequency magnetic fields locally and investigate EEG power spectrum alters at the frequency of stimulation. EEG relative power spectrum were evaluated at 3, 5, 10, 17, and 45 Hz frequencies at T4, T3, F3, Cz, and F4 points, respectively, when these points were exposed to magnetic fields with similar frequencies and 100 μT intensity. The paired t-test results showed that power value of EEG did not alter significantly at the frequency of stimulation (P<0.05). Further, significant changes in different EEG bands caused by locally exposing to ELF-MF in different points of brain were observed. The changes in the EEG bands were not limited necessarily to the exposure point.     

Phencyclidine Disrupts the Auditory Steady State Response in Rats

The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.     

Study of the frequency parameters of EEG influenced by zone-dependent local ELF-MF exposure on the human head

It has been reported that human subjects exposed to electromagnetic fields exhibit changes in human EEG signals at the frequency of stimulation. The aim of the present study was to expose different parts of the brain to extremely low-frequency magnetic fields locally and investigate EEG power spectrum alters at the frequency of stimulation. EEG relative power spectrum were evaluated at 3, 5, 10, 17, and 45 Hz frequencies at T4, T3, F3, Cz, and F4 points, respectively, when these points were exposed to magnetic fields with similar frequencies and 100 μT intensity. The paired t-test results showed that power value of EEG did not alter significantly at the frequency of stimulation (P < 0.05). Further, significant changes in different EEG bands caused by locally exposing to ELF-MF in different points of brain were observed. The changes in the EEG bands were not limited necessarily to the exposure point.     

Neuropeptide Y: prejunctional inhibition of vagally induced contractions in the guinea pig trachea

The effects of neuropeptide Y (NPY) on the contractile response to vagus nerve stimulation at different frequencies was studied in an isolated tracheal tube preparation from guinea pig. NPY had no effect on basal smooth muscle tension or on the contractile effect of carbachol, but inhibited vagally induced contractions in a concentration-dependent manner with a greater inhibition at low frequencies than at high. We suggest that the effect is exerted prejunctionally.     

Cerebral responses of healthy humans to rhythmic transcranial magnetic stimulation of different intensities

The effect of rhythmic transcranial magnetic stimulation (rTMS) of different intensities (single superthreshold rTMS more intense than 1.2 T and subthreshold one with an intensity of 70–80% of the motor threshold) of sagittal premotor cortical areas on the human functional activity was estimated in eight volunteers on the basis of combined EEG, neuropsychological, and hemodynamic examinations. The objectives of the study included the selection of the frequency of activating stimulation and revision of the objective EEG criteria of rTMS efficiency. It has been demonstrated that analysis of the EEG response to photostimulation at different frequencies is efficient in selecting the rTMS frequency. The EEG coherence is one of the most informative characteristics of the rTMS effect on central neurodynamics. The functional effects of stimulation (activating or inhibitory) have been shown to depend on the initial level of intercentral coherent relationships It has been found that rTMS of the sagittal premotor cortex causes definite changes in the functional activity of a healthy brain different from those caused by placebo. These changes are greater in the left hemisphere (in the form of intrahemispheric changes in coherence and depend on the stimulation intensity (superor subthreshold) and the initial state. The vascular factor has been shown to play an important role in the formation of cerebral responses to rTMS.     

Spike amplitude modulation at high stimulation frequencies

Summary A technique of mathematical analysis has been developed for studying spike amplitude variations, during natural sinusoidal stimulation. This technique is suitable even when stimulation frequency is of the same order as, or higher than, the cell firing rate.We used this technique for the cat's retinal ganglion cells. The results agree with the previous ones (Gestri et al., 1967) at low stimulation frequencies and show that the spike amplitude modulation occur even at high frequencies, the phase shift between spike amplitude and firing probability being a function of the stimulation frequency.     

Influence of a period of inactivity on the duration of post-rest action potentials of the mammalian working ventricular myocardium in correlation to the preceding stimulation frequency

Experiments were carried out on the working right ventricular myocardium of adult cats, guinea-pigs and rabbits. Membrane voltage was recorded by the glass microelectrode technique and the preparations were stimulated with frequencies of 5, 1 and 0.2 Hz. After a steady state had been reached, a pause (TP) lasting 10-600 s was interpolated. The influence of TP on the duration (D) of post-rest action potentials (AP) was studied; the effect of the pause was measured at electric zero level (D0) and at further repolarization levels (-20, -40 and -60 mV, given here as D-20, D-40 and D-60). At 1 and 0.2 Hz frequency, the cat myocardium displayed lengthening of the AP proportional to the duration of the pause; at 5 Hz frequency, D0 reacted by lengthening up to TP = 120 s and to further pauses by slight shortening. D-60, at all frequencies, lengthened throughout the whole of the given TP range. The rabbit myocardium, at all the given frequencies, reacted up to TP = 60-120 s by marked shortening of post-rest AP at all repolarization levels; with longer pauses the AP lengthened. At 5 Hz frequency the guinea-pig myocardium reacted similarly to the cat myocardium; at the lower stimulation frequencies, the pause-induced changes in the post-rest AP were less strongly expressed. In all the given types of myocardium, the most pronounced post-rest AP reactions were those at electric zero level (the plateau phase of the AP); towards more negative repolarization values and with lower pre-pause stimulation frequencies they were less strongly expressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional studies of nerve projections in the canine intestine

An in vivo model has been developed to study nerve connections in the canine intestine, using spread of field stimulated contractions recorded proximally and distally with strain gauges and local intra-arterial injections of drugs. Excitation spread orally for several centimetres, more effectively at lower frequencies of field stimulation. This excitation was blocked by local hexamethonium or by a combination of atropine and naloxone (each of which reduced the contractions). Distal excitation occurred after a longer delay than oral excitation; during the delay there was frequently an initial relaxation response. Distal excitation was greater at higher frequencies of field stimulation, but like oral excitation it was blocked by hexamethonium or by a combination of atropine and naloxone. Distal relaxation responses were unaffected by atropine or naloxone, but were abolished by hexamethonium. "Off" contractions, those that followed cessation of field stimulation, occurred at higher frequencies of field stimulation proximally and distally near the site of field stimulation and were blocked by atropine but not by naloxone or hexamethonium. The effects of all agents given locally extended beyond the sites of injection. These results suggest that a chain of cholinergic nerves with nicotinic synapses transmit excitation orally and distally to circular muscle; these effects seem to be facilitated proximally and distally by opioid nerves and to be inhibited initially distally by a noncholinergic mechanism. Explanations of these findings are proposed.     

电刺激迷走神经对蟾蜍心率和心率变异的影响

目的:观察不同频率迷走神经刺激对蟾蜍离体心脏的心率及心率变异的影响。方法:将蟾蜍心脏和右侧迷走交感干离体后,以不同频率电刺激神经,记录心电图曲线并作心率变异性(HRV)分析。结果:交感神经阻断后,电刺激迷走交感干,心率(HR)显著下降(P0.01),全部正常心动周期的标准差(SDNN)和相邻正常心动周期差值的均方根(RMSSD)显著升高(P0.01),不同频率刺激组之间没有明显差异;与对照组相比,各指标变化较大;给药组0.2Hz时高频(HF)显著升高(P0.01),低频/高频比值(LF/HF)明显降低(P0.05),0.8Hz时HF和LF/HF接近刺激前水平。结论:一定范围内增加刺激频率,迷走神经降低心率的作用增强;没有交感神经调节条件下的迷走神经对心率和心率变异的调节可能存在不同的机制。     

The role of inhibition in shaping the type of single neuron responses in the auditory system of the frog

The responses of single neurons of the auditory center in the frog mesencephalon to tonal stimuli of varying frequencies have been studied. It has been found that some neurons which respond to the signal of the characteristic frequency (CF) by a long-lasting discharge respond to tones of higher frequencies only at the start of stimulation. It is shown, that the tones giving rise to a phasic response inhibit impulsation brought about by the action of the CF tone.Acoustics Institute, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 3, pp. 236–241, May–June, 1970.     

Peptide-containing neurons intrinsic to the gut wall

Summary Nerve fibers containing substance P, VIP, enkephalin or somatostatin are numerous in the porcine gut wall. They are particularly numerous in the submucosal and myenteric plexuses where peptide-containing cell bodies are also observed. Peptide-containing nerve fibers occur also in the vagus nerves, suggesting that the gut receives an extrinsic supply of peptidergic nerves. The extrinsic contribution to the peptide-containing nerve supply of the gut wall has not yet been quantitatively assessed. In an attempt to clarify this question pigs were subjected to bilateral subdiaphragmatic vagotomy. Another group of animals was subjected to complete extrinsic denervation by autotransplantation of a jejunal segment. The pigs were killed at various time intervals after the operations; the longest time interval studied was four months. Following vagotomy the innervation pattern of the jejunum appeared completely unaffected. Following complete extrinsic denervation the adrenergic nerve fibers disappeared, while peptide-containing and acetylcholinesterase-positive nerve fibers remained apparently unaltered. This was confirmed chemically in the case of substance P.The motor activity of smooth muscle from the jejunum was studied in vitro. At low stimulation frequencies the smooth muscle from control jejunum responded by relaxation; upon cessation of stimulation a contraction occurred. With increasing stimulation frequencies the duration of the relaxation decreased; at high frequency stimulation only a contraction was recorded. In the autotransplant low frequency stimulation induced no or only a weak relaxation; high frequency stimulation induced contraction. After cholinergic and adrenergic blockade, the muscle responded with relaxation at all frequencies; the response was similar in innervated and denervated specimens. On the whole, the effects of extrinsic denervation on the motor activity of smooth muscle from porcine jejunum were minor, possibly reflecting the high degree of autonomy of the gut.     

Botox produces functional weakness in non-injected muscles adjacent to the target muscle

Botulinum type-A (BTX-A) neurotoxin exerts a paralytic effect on muscles and is used increasingly to treat a variety of muscle spasticity disorders. While its pathogenesis for muscle-induced weakness has been well elucidated, the functional effects of BTX-A administration are incomplete. Specifically, weakness as a function of muscle length and stimulation frequency has only been investigated qualitatively in a few muscles and the possible effect of the toxin on non-target muscles, although considered possible based on laboratory experiments, has not been studied widely and the functional implications remain unknown. Therefore, the purpose of this study was to measure the functional implications of BTX-A on force production and possible weakness of a target muscle and a non-injected neighbouring muscle. The cat soleus was chosen as the target muscle and was injected with 3.2-3.5U of BTX-A/kg in one hind limb, while the soleus of the other hind limb served as a non-injected control. Force-length properties within and exceeding the functional range of motion were determined at frequencies of stimulation of 10, 30 and 50Hz. Force-length properties of the adjacent non-injected plantaris were also determined in the experimental and contralateral hind limb. Four weeks following BTX-A injections, peak soleus forces were decreased by 30% (50Hz), 29% (30Hz) and 29% (10Hz) and peak plantaris forces were decreased by 11% (50Hz), 16% (30Hz) and 16% (10Hz), in the experimental compared to the contralateral hind limb. Absolute BTX-associated force loss was significantly different at all frequencies of stimulation and all lengths for the soleus, while in the plantaris there was a significant force loss across long (> or = -4mm) but not short muscle lengths. Decreases in peak force were independent of the stimulation frequency. We concluded from the results of this study that BTX-A injection in the target muscle caused a measurable effect on force production and that force production was decreased in non-target neighbouring muscles at and near lengths of peak force production. These results are of particular importance in therapeutic procedures where isolated muscles are targeted for treatment. They should also be considered in neurophysiological studies in which BTX-A injections are used to selectively diminish muscle function.     

Effect of caffeine on skeletal muscle function before and after fatigue

We studied the effect of caffeine on voluntary and electrically stimulated contractions of the adductor pollicis muscle in five adult volunteers. Caffeine (500 mg) was administered orally in a double-blind fashion. Electrical stimulation of the ulnar nerve was performed at 10, 20, 30, 50, and 100 Hz before and after a sustained voluntary contraction held at 50% of the maximal voluntary contraction (MVC). A brief tetanus at 30 Hz was also performed to calculate relaxation rate in the fresh muscle. Contractile properties, relaxation rate, and endurance were then assessed after caffeine and placebo, as well as the response of the fatigued muscle to different frequencies of stimulation. There was no difference in the maximal tension obtained with electrical stimulation (T100) or in the MVC between placebo and caffeine. The tensions developed with electrical stimulation at lower frequencies increased significantly with caffeine ingestion, shifting the frequency-force curve to the left, both before and after fatigue. Mean plasma caffeine concentration associated with these responses was 12.2 +/- 4.9 mg/l. We conclude that caffeine has a direct effect on skeletal muscle contractile properties both before and after fatigue as demonstrated by electrical stimulation.     

Physiological properties of the penis retractor muscle of Aplysia

The properties of the penis retractor muscle of Aplysia have been studied using intracellular, sucrose gap and tension recording. The fibers are of the invertebrate smooth muscle type and exhibit slow contractions which occur spontaneously or in response to stretch in isolated preparations. Individual muscle fibers are innervated by excitatory and inhibitory axons. A variety of sizes of excitatory and inhibitory junctional potentials can be recorded from them. The innervation is probably diffuse and functionally polyneuronal. The fibers are electrically coupled, permeable to potassium and chloride at rest, and exhibit no overshooting active responses. The muscle shows graded responses of depolarization and contraction proportional to strength of nerve stimulation. Facilitation and depression of junctional potentials are seen with various frequencies of nerve stimulation. Post-tetanic potentiation occurs with nerve stimulation at frequencies from 2 to 50 Hz and is suppressed in the presence of increased extracellular calcium concentrations.     

Alternans and 2:1 rhythms in an ionic model of heart cells

ECG alternans is commonly held to be an indicator of electrical instability of the heart, but the development of alternans has not yet been fully understood theoretically. We investigate the onset of alternans and 2:1 rhythms for stimulation at increasing frequencies in the Beeler-Reuter model, a simple ionic model of cardiac tissue. We find hysteresis and bistability at the onset of alternans; well-timed stimuli can switch between the two limit cycles. We determine quantitatively the effect of blocking specific ionic currents. Moreover, we find that calcium buffers generally promote alternans.     

Entrainment in pacemakers characterized by a V-shaped PRC

The behaviour of a class of pacemakers characterized by a V-shaped PRC has been determined, for all possible frequencies and amplitudes of stimulation. The analytical study of the phase transition equation reveals that all rhythmic stimuli, but for a set of measure zero, give rise to entrainment. The ratio between firing and stimulation frequencies is a generalized Cantor function of the ratio between spontaneous and stimulation frequencies. A procedure to compute the detailed input/output pattern that underlies each entrainment ratio is given. Finally, the neurophysiological assumptions and implications of the results obtained are discussed.     

Low frequency-dependent mechanism of the M2 receptor function on vagally mediated bronchoconstriction in rabbits in vivo.

The present study was carried out to investigate whether there is the difference between low and high frequencies of vagal stimulation on the functional appearance of M2 receptors in the rabbit. The animals were anesthetized, artificially ventilated and bilaterally vagotomized. Bilateral vagus nerve stimulation (5 to 30 Hz) for 30 sec caused bronchoconstriction (measured as an increase in R(L) and a decrease in Cdyn) in a frequency-dependent manner. The bronchoconstriction evoked by ACh injection (1 and 3 microg/kg) was dose-dependent. Although administration of methoctramine (50 and 300 microg/kg), a selective M2 receptor antagonist, had no significant effect on ACh-induced bronchoconstriction, methoctramine dose-dependently augmented the R(L) and Cdyn responses to vagal stimulation at 5-15 Hz but did not potentiate bronchoconstrictive responses to the stimulation at 30 Hz. Administration of [D-Pro2, D-Try(7,9)]-SP (0.5 mg/kg, a selective tachykinin receptor antagonist) that had no significant effect on the R(L) and Cdyn responses to vagal stimulation (5-15 Hz) attenuated the bronchoconstrictive response to the stimulation at 30 Hz. Conversely, thiorphan (2 mg/kg, a neutral endopeptidase inhibitor) potentiated the bronchoconstriction evoked by vagal stimulation at 30 Hz only. These results suggest that M2 receptors function as the inhibitory receptors in the bronchoconstrictive response to vagal stimulation at the lower frequencies (5-15 Hz), but that the M2 receptor antagonism is diminished when vagal stimulation at a higher frequency (30 Hz) results in the release of SP from the lungs.