Changes produced in neuronal excitability by subthreshold depolarization as a possible mechanism of interval selective relationships within the central nervous system

A neuronal process was identified inLymnaea stagnalis nerve cells which may be viewed as one of the mechanisms underlying the interval selectivity previously described in research into the functional relationships between mammalian brain cells. This process takes the form of regularly-occurring changes in excitability resulting in a high probability (of 0.6–1) of neuronal spike response to what had previously been subthreshold depolarizing current pulses following similar subthreshold (conditioning) pulses at intervals specific to each individual neuron. It was found that the cycle of change in neuronal excitability following threshold depolarization did not arise from temporal summation of electrotonic local or postsynaptic neuronal potentials; it was an endogenous (cytoplasmic) process insensitive to transmitter (acetylcholine) application but altering irreversibly under the effects of bombesin, one of the modulator peptides.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad; Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologya, Vol. 21, No. 3, pp. 291–299, May–June, 1989.     

Modulation of Activity of One Neuron by Subthreshold Slow Potentials in Another in Lobster Cardiac Ganglion

A direct demonstration is given of interaction between specific neurons without impulses, via graded slow potentials electrotonically spread from one cell to another. Repetitive polarizing or depolarizing current pulses of 50 to 200 msec. and subthreshold intensity were passed through an intracellular electrode in the soma of a follower cell of the isolated ganglion. When the frequency is near the natural rhythm of impulse bursts corresponding to heart beats and arising in a pacemaker cell 5 to 10 mm. posteriorly, the bursts rapidly become synchronized with the pulses. The effect disappears upon withdrawing the intracellular electrode. Brief pulses or full spikes in the follower are not effective. Hyperpolarizing long pulses attract the burst to a fixed period after the end of the pulse, depolarizations after the beginning of the pulse. The natural rhythm promptly reappears when the pulses are stopped and occasionally breaks through during weak repetitive pulses. Current pulses in postsynaptic cells also alter the threshold of a presynaptic neuron to externally applied stimuli. Some kind of direct, low resistance pathway for electrotonic spread, discriminating against spikes because of their brevity, is inferred, providing a basis for subthreshold interaction which is specific and not by way of a field effect. Due to the sensitivity of modulation of ongoing rhythms, electrotonic currents can be effective even after decrementing over several millimeters.     

Secondary Rhythms of Cardiac Activity in Rat Ontogeny

Endogenous periodic oscillations of the heart beat rate are described in rat pups aged 3–4, 7–8, 10–11, 13–14, 21–22 days and 1.5 month after birth. These oscillations have all characteristic features established earlier for the secondary rhythms of endogenous contractile activity in the wall of various regions of the gastrointestinal tract and for bursts of spontaneous somatomotor excitation in the early postnatal ontogeny of rats: a multi-stage organization, inconstancy, irregularity of components. In frequency spectra of secondary oscillations of the heart rate obtained by means of fast Fourier transform of R–R intervals of the periodogram, age-related changes of the spectral frequency power are demonstrated in 4 ranges, 0.01–0.03, 0.03–0.1, 0.1–1.0, and 1.0–2.5 Hz, which correspond to the about-one-minute, decasecond, and about-one-second waves of the heart rhythm oscillations and to sinus arrhythmia. It is shown that the dominating frequencies of the secondary rhythms in each range do not have regular age-related changes, which is characteristic of all endogenous secondary rhythms.     

Age-Specific Features of Physiological Responses of Five- to Seven-Year-Old Children to Working with a PC

The functional status of the central nervous system (CNS), the character of the regulation of the heart rhythm, and general operative efficiency were studied in 96 five-, six-, and seven-year-old children working with a personal computer (PC). The study revealed certain age-specific features in the childrens' physiological reactions to this work: five-year-old children differed significantly from their six–seven-year-old counterparts both in their basal physiological status and in their reactions to working with a PC. Five-year-olds also displayed the least favorable time of the CNS functional parameters and operative efficiency (60% of these children displayed various signs of fatigue). Similar age-specific features were also found in the regulation of the heart rhythm while working with a PC. In spite of the fact that 58% of all the children examined showed an optimal strength of their autonomic regulatory mechanisms, a highly stressed state of the regulation of the heart rhythm was observed in 21 and 28% of five-year-old children before and after working with a PC, contrasted with 10–16 and 17–25% in six- to seven-year-old children, respectively. It was concluded that the physiological and hygienic norm setting for children working with a PC should consider the five-year-olds as a separate group.     

Olfactory rhythm in the electrical activity of the human amygdaloid nucleus

Summated electrical activity of the human amygdaloid nucleus was investigated in the neurosurgical clinic by chronically implanted electrodes. It was found that odoriferous stimulation of this structure produced bursts of rapid rhythm (20–30 cps, 30–50 µV). The quasisinusoidal waves of olfactory rhythm consist of sinusoidal components which are more pronounced within the 20–30-Hz frequency range. Spindling of 1–3 sec duration occurs at the end of inhalation and the beginning of exhalation in time with breathing. During monorhinal breathing this activity, whose amplitude depends on degree of olfactory stimulation, can only be recorded ipsilaterally. Room air also activates the amygdaloid nucleus, but less strongly than odoriferous substances: No characteristic odor-dependent differences were discovered in the frequency range of the olfactory rhythm within a 20–30-Hz band.Institute of Physiology, Kiev State University, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 1, pp. 61–69, January–February, 1986.     

Contractile Activation in Frog Skeletal Muscle

Contractile activation was studied in frog single muscle fibers treated with tetrodotoxin to block action potentials. The membrane potential in a short segment of the fiber was controlled with a two-electrode voltage clamp, and the contractile response of superficial myofibrils in this segment was observed microscopically. The strength-duration relation for contractile activation was similar to that reported by Adrian, Chandler, and Hodgkin (1969); at 3.9°C, the contraction threshold was –44 mV for long depolarizing pulses (100-ms) and increased to +64 mV for 2-ms depolarizations. Hyperpolarizing postpulses shifted the threshold for 2-ms pulses to more positive values, and a similar, but smaller, effect was produced by hyperpolarizing prepulses. The decay of excitability following subthreshold pulses showed two apparently distinct components; at 3.9°C, excitability fell to 50% of its initial value within 4 ms, while the subsequent decline of excitability proceeded with a half-time of about 20 ms.     

Formal properties of the circadian rhythm of locomotor activity in Japanese quail

Summary Japanese quail have a circadian rhythm of locomotor activity whose free-run period () in constant darkness (DD) was 22.5±0.1 h (45). A phase response curve of typical form was obtained by illuminating the free-running rhythm with single 1 h light pulses. Using entrainment theory a derived phase response curve was calculated from the phase relationships between the locomotor rhythm and 1 h light periods in light-dark cycles of various lengths (T). Although the limits of entrainment to theseT cycles differed slightly from those predicted, there was a close correlation between the two phase response curves. The phase relationships between the locomotor rhythm and 1–9 h photoperiods in 24 h cycles were in general accord with a prediction based on the short free-run period and the relative sizes of the delay and advance portions of the phase response curve for 1 h light pulses.     

Respiratory Cardiac Arrhythmia in Postnatal Ontogenesis of Rats

Development of the respiratory cardiac arrhythmia and the role of parasympathetic nervous system in its origin have been studied in rats aged from 4–6 days to 6 months of life. In rat pups of the first week of life, small fluctuations of cardiac rhythm were observed with the frequency close to fluctuations of respiratory rhythm. However, at this age they had neither regular character nor clear connection with phases of the respiratory cycle. On the 2–3rd week the amplitude of fluctuations rose and their association with respiration was established; however, unlike the respiratory arrhythmia observed in other animals and human, in rat pups there was deceleration but not acceleration of heart beating. By to the 6-week age the respiratory arrhythmia reached the maximal values, then its amplitude began to decrease. Bilateral transection of the vagus nerves in rat pups did not cause reduction of the respiratory arrhythmia. Thus, in rats the central influences on the heart can be transduced by bypassing the system of vagus nerves.     

Change of Parameters of Functioning of the Cardiovascular and Respiratory Systems in Rats of Different Ages under Effects of Low Doses of the Cholinesterase Inhibitor Phosphacol

In the 4-day old rat pups and adult animals there were studied effects of subacute and acute phosphacol intoxication at the doses producing and not producing inhibition of aetylcholinesterase on ECG parameters and respiration rate. Analysis of the heart rhythm variability (HRV) was performed using an original program designed in the Labview media. The frequency diapason of cardiointervals was divided as follows: the high-frequency component (HF)-0.8-2.5 Hz, the low-frequency (LF, waves of the II order)-0.8-0.3 Hz; frequencies lower than 0.3 Hz-VLF (slow waves of the III order). Under the conditions of the subacute intoxication the heart rate frequency in the 4-day old and in adult rats increases by 36% and 13%, respectively, the respiration rate frequency increases by 73% in the newborn and does not change in adult rats. The VHR analysis indicates an increase of the tone of the parasympathetic nervous system. The level of the sympathetic activity somewhat increases in adults, but decreases in the 5-day old rat pups, which leads to an essential shift of the vagosympathetic balance towards predominance of parasympathetic influences. In adult rats, unlike the newborns, the role of the humoral-metabolic factors in regulation of the cardiac rhythm and vasomotor reactions increases significantly. Remarkably, the decrease of the nervous sympathetic effects in the rat pups leads to the positive chronotropic effect and stabilization of the cardiac rhythm. Acute phosphacol intoxication (doses of 0.25 and 1 µg/kg) is studied in the 4-day old rat pups. The low dose of the drug leads to development of a moderate bradycardia without disturbances of the cardiac rhythm. The high phosphacol dose produces pronounced bradycardia; on its background there develops a long-term transitory arrhythmia representing complexes of the heart rhythm, which alternate in the decasecond or nearminute rhythm and are separated by periodicity that is one order slower. We observed such rhythm earlier during activation of central N-cholinoreactive structures and development of bilateral pneumothorax. Results of the present study allow stating the paradoxical heart rhythm not as agonic, non-peculiar to the “living” organism, but as a special form of functioning of cardiac pacemakers due to disturbances of the heart regulatory mechanism.__________Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 2, 2005, pp. 160–167.Original Russian Text Copyright © 2005 by Kuznetsov, Goncharov, Glashkina.     

The role of temperature in the regulation of the circadian rhythm of CO2 fixation in Bryophyllum fedtschenkoi

Detached leaves of Bryophyllum fedtschenkoi Hamet et Perrier kept in normal air show a single period of net CO₂ fixation on transfer to constant darkness at temperatures in the range 0–25 °C. The duration of this initial fixation period is largely independent of temperature in the range 5–20 °C, but lengthens very markedly at temperatures below 4 °C, and is reduced at temperatures above 25 °C. The onset of net fixation of CO₂ on transfer of leaves to constant darkness is immediate at low temperatures, but is delayed as the temperature is increased. The ambient temperature also determines whether or not a circadian rhythm of CO₂ exchange occurs. The rhythm begins to appear at about 20 °C, is most evident at 30 °C and becomes less distinct at 35 °C. The occurrence of a distinct circadian rhythm in CO₂ output at 30° C in the absence of a detectable rhythm in PEPCase kinase activity shows that the kinase rhythm is not a mandatory requirement for the rhythm of PEPCase activity. However, when it occurs, the kinase rhythm undoubtedly amplifies the PEPCase rhythm.Abbreviation PEPCase phosphoenolpyruvate carboxylase We thank the Agricultural and Food Research Council for financial support for this work.     

Do circulating plasma AVT and/or cortisol levels control pulsatile urea excretion in the gulf toadfish (Opsanus beta)?

Previous work has shown that pulsatile urea excretion at the gills of the gulf toadfish is due to periodic activation of a facilitated diffusion transport system with molecular and pharmacological similarity to the UT-A transport system of the mammalian kidney. In mammals, AVP and glucocorticoids are two important endocrine regulators of this system. The present study focused on the potential role of circulating AVT (the teleost homologue of AVP) and cortisol levels as possible triggers for urea pulses. Long-term (34–84 h) monitoring of plasma levels by repetitive sampling at 2-h intervals from chronic cannulae in individual toadfish demonstrated that circulating AVT concentrations are low (10⁻¹²–10⁻¹¹ M), and show no relationship to the occurrence of natural urea pulses. In contrast, plasma cortisol levels decline greatly prior to natural pulses and rise rapidly thereafter. AVT injections into the caudal artery or ventral aorta elicited pulse events, but these were extremely small (1–10%) relative to natural pulses, and occurred only at unphysiological dose levels (10⁻⁹ M in the plasma). AVP was a partial agonist, but isotocin, insulin-like growth factor-1, and atrial natriuretic peptide were without effect at the same concentration. Artificially raising plasma cortisol levels by cortisol injection tended to reduce responsiveness to AVT. Pharmacological reduction of plasma cortisol levels by metyrapone injection elicited small pulses similar to those caused by AVT. Following such pulse events, AVT was ineffective in inducing pulses. We conclude that decreases in circulating cortisol play an important permissive role in urea pulsing, but that circulating AVT levels are not involved.     

Neural control of heartbeat in the pteropod mollusk Clione limacina

The heart of the pteropod molluskClione limacina is innervated by the median nerve arising from the left abdominal ganglion. Five neurons sending axons to the heart have been identified in theClione central nervous system with retrograde cobalt or Lucifer yellow staining. Neuron H1 located in the left pedal ganglion produced an excitatory effect on heart beat. Stimulation of three neurons, H2–H4, situated in a compact group in the medial region of the left abdominal ganglion, led to inhibition of cardiac contraction, while H5, located in the caudal region of the left abdominal ganglion, did not affect heart beat. The activity of efferent cardiac neurons (ECN) was found to be related to the operation of the locomotor rhythm generator. Spontaneous or reflex depression of the latter was found to inhibit neuron H1 and activate units H2–H4. The behavior of these ECN accounts for the positive correlation between heart operation and locomotor activity inClione limacina.Institute of Research on Information Transmission, Academy of Sciences of the USSR, Moscow, M. V. Lomonosov State University, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 2, pp. 185–192, March–April, 1989.     

Translocation of neural modulators a second category of nerve signal

Translocation of substances that modulate cell-firing in the brain occurs in neural systems. Some of these substances are considered to be intermediary in the actions of neurotransmitters, and they or their metabolites undergo translocation both intracellularly and extracellularly, in and among established neural structures. The movements, in suitable circumstances, are now proposed to have the status of signal-transmission complementary to that of the orthodox nerve impulse, but traveling at 10^–6–10^–7 times its speed.     

Evoked potentials of the human cerebral cortex to perceptible and imperceptible sound stimuli

Evoked potentials averaged with the help of an electronic computer (AEP) to brief sound stimuli of subthreshold (3–10 dB below the threshold of the signal's audibility), threshold, and superthreshold (10–60 dB above the threshold) intensity were recorded from the vertex and occipital region of the cranium in healthy people. The dynamics of the changes in the AEP with an increase in the intensity of the sound from subthreshold to superthreshold (60 dB) values was shown. The time and amplitude parameters of AEP to imperceptible and perceptible sound stimuli differed significantly. The most constant, and in many cases the only component of the AEP to an imperceptible stimulus was a long-latent, low-amplitude, slow positive oscillation. The participation of the cerebral cortex in the neural mechanisms of reactions to imperceptible sound stimuli is discussed.V. P. Serbskii Central Scientific-Research Institute of Forensic Psychiatry, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 2, pp. 115–122, March–April, 1971.     

Fractal dynamics in circadian cardiac time series of corticotropin-releasing factor receptor subtype-2 deficient mice

Non-linear fractal analysis of circadian 24 hr heartbeat interval time series was performed in corticotropin releasing factor receptor-subtype 2 (CRFR2) deficient mice. We hypothesized that, as a result of its central as well as its peripheral expression, CRFR2 would mediate or interfere with the circadian rhythmicity. The dynamical properties of cardiac interbeat intervals were expected to be different between CRFR2 (+/+) and CRFR2 (–/–) mice when studied over an extended circadian 24 hr cycle. The dynamics of neurocardiac control were found to remain remarkably stable throughout the circadian cycle. In disagreement with the initial hypothesis, the dynamical properties underlying the cardiac control process were common to both CRFR2 (+/+) and CRFR2 (–/–) mice suggesting that control of heart rate does not rely on the elaborate interaction of the CRFR2-sensor and its intrinsic feedback arrangement. Lack of expression of CRFR2 would not compromise cardiac control and its dynamical output or is subserved by other, unknown mechanisms. Functional integrity of CRFR2 would not constitute an indispensable requirement of physiologic cardiac control. The circadian rhythm of heart rate is generated centrally and is independent of expression of CRFR2. While `normal' strain C57BL/6N mice exhibit a circadian dark/light cycle of heart rate, absence of circadian fluctuations in transgenic CRFR2-mice (both +/+ and –/–) and `normal' strain C57BL/6J mice points at the importance of other deficiencies that may be related to a common genetic background. Mutant mice that share a common 129SvJ- or C57BL/6J-derived genetic background may not present an optimal model for physiological studies of cardiovascular control.     

Effects of cAMP,theophylline, imidazole,and 4-(3,4-dimethoxybenzyl)-2-imidazolidone on the leaf movement rhythm of Trifolium repens—a test of the cAMP-hypothesis of circadian rhythms

The period length of the leaf movement rhythm of Trifolium repens L. is lengthened by continuously offered cAMP (0.5–1.0 mol m^-3) and theophylline (0.5–4 mol m^-3). At the higher concentrations this effect is more pronounced and the rhythm damps out faster. Imidazole (0.5 and 1 mol m^-3) has no effect on the period length; however, after 5 mol m^-3 the rhythm is abolished. Offered as 4 h pulses the resulting phase response curves for cAMP and imidazole are similar and show delays of up to 4 h during the day position of the leaves. Theophylline pulses lead to delays of up to 5 h during closure and advances of up to 3 h during opening. No phase shift is brought about by 4-(3,4-dimethoxybenzyl)-2-imidazolidone. The results do not support the cAMP-model of the circadian clock which has been proposed by Cummings (J. theor. Biol. 55, 455–470; 1975). The effect of the substances tested could, however, be based upon influences on the transport of Ca²⁺.Abbreviations ATP adenosine triphosphate - cAMP cyclic adenosine 35 monophosphate - AMP adenosine 5 monophosphate - AC adenyl cyclase - PDE phosphodiesterase - LL continuous light     

Dämpfung der Gewebeatmung (QO2) von Mäuseleber durch künstliche Impulsstrahlung

Zusammenfassung In einem gegen die natürliche Langwellenstrahlung abgeschirmten Versuchsraum wurde die Atmung von Mäuselebergewebe in künstlich erzeugten elektromagnetischen Feldern gemessen. Unter der Einwirkung von zyklonale Wetterlagen simulierenden Programmen (30–100 pulses sec^–1, > 100 mV m^–1, 10–100 kHz) ergab sich im Vergleich zu den Kontroll-QO₂-Werten eine signifikante Dämpfung der Gewebeatmung um 42% ± 2,8% (p<0,001). Die Applikation eines H-Feld-Programms blieb ohne Wirkung. Programme mit Simulierung antizyklonaler Wetterlagen(1–3 pulses sec^–1, <10 mV m^–1, 10 kHz) hatten ebenfalls keinen Einfluss auf die Atmungsgeschwindigkeit der Mäuseleber.

---

In a room completely shielded against long wave radiation, liver tissue of mice in a Warburg apparatus was exposed to artificial electromagnetic radiation simulating cyclonic and anticyclonic weather. Under the influence of simulated cyclonic weather programs (30–100 pulses sec^–1, > 100 mV m^–1 10–100 kHz) a significant decrease (42% ± 2,8%) of the respiration rate of the liver tissue was found, compared with the control QO₂ (p < 0,001). The application of a cyclonic weather H-field program had no effect. Simulated anticyclonic weather (1–3 pulses sec^–1, < 10 mV m^–1, 10 kHz) also failed to produce a demonstrable effect on the respiration rate of mouse liver tissue.

---

Resume Dans un local absolument protégé contre l'irradiation naturelle par ondes longues, des tissus de foie de souris ont été exposés, dans un appareil de Warburg, à des impulsions électromagnétiques artificielles, correspondant à celles de temps cyclonal et anticyclonal. Sous l'influence des programmes artificiels simulant le temps cyclonal(30–100 pulses sec^–1, > 100 mV m^–1, 10–100 kHz), il a été constaté une inhibitation significative de la respiration tissulaire de 42% ± 2,8% comparée aux valeurs du QO₂ de contrôle (p < 0.001). L'application d'un temps cyclonal-"H-field"-programme séparé, est demeuré sans effet. De même. les signaux de temps anticyclonal(1–3 pulses sec^–1, < 10 mV m^–1, 10 kHz), n'ont eu aucune influence démonstrable sur la vitesse de respiration du fois de souris.

     

Phenological records of English garden plants in Leeds (Yorkshire) and Richmond (Surrey) from 1946 to 2002. An analysis relating to global warming

Graphical analysis of first-flowering dates of selected garden plants 1946–2002 shows an earlier trend, which appears to be linked to temperature and global warming. Some species, however, seem to buck this trend, which may be linked to photoperiodic response. Combined graphs of species selected at intervals throughout the calendar year reveal a rhythm or wave of several years in Leeds 1946–1962 and a less marked rhythm in Richmond 1961–2002.     

Early Effects of Neonatal Rat Desympathization on Secondary Heart Rhythms

Neonatal Wistar rats for the first 3 weeks of life were injected intraperitoneally with isobarine every other day. The single doze was 40 mg/kg. Control animals were injected with saline. Degenerative changes in sympathetic ganglia were evident as early as in the 10-day old animals and increased by 18–19 days. The heart rate in the desympathized animals was lower than in control from 10–11 to 18–19 days, but by the end of the 3rd week the differences were eliminated. The same occurred with respiration rate. At same terms there was an essential decrease of amplitude of the heart rate high-frequency fluctuations synchronous with respiration and of the periodogram slow waves with the period about 1 min. Using the method of fast Fourier transform, the power spectra of heart rate fluctuations (secondary heart rhythms) in 5 frequency ranges (0–0.01, 0.01–0.03, 0.03–0.1, 0.1–1.0, and 1.0–2.5 Hz) were calculated. Desympathization leads to a decrease of the fluctuation power in all ranges, but in the ultralow-frequency range this decrease is the least pronounced, which suggests the presence of non- sympathetic mechanisms in their genesis. The greatest changes occur in the middle-frequency area. In all cases, differences from control values increase from the 10–11th to the 18–19th days, after which a tendency for restoration is observed, in spite of an enhancement of processes of degeneration of sympathetic neurons. This indicates an activation of the compensatory mechanisms, due to which consequences of desympathization are partially smoothed at distant terms of studies.     

Effects of Desmin Gene Knockout on Mice Heart Mitochondria

In heart tissue from mice lacking the intermediate filament (IF) desmin, mitochondria show an abnormal shape and distribution (Thornell et al., 1997). In the present study we have isolated heart mitochondria from desmin null (D–/–) and control (D+/+) mice, and analyzed their composition by SDS–PAGE, immunoblotting, and enzyme measurements. We found both in vitro and in situ that the conventional kinesin, the microtubule-associated plus-end directed motor, was frequently associated with D+/+ heart mitochondria, but not with D–/– heart mitochondria, suggesting that the positioning of mitochondria in heart is a dynamic event involving the IF desmin, the molecular motor kinesin, and, most likely, the microtubules (MT) network. Furthermore, an increased capacity in energy production was found, as indicated by a threefold higher creatine kinase activity in heart mitochondria from D–/– compared to D+/+ mice. We also observed a significantly lower amount of cytochrome c in heart mitochondria from D–/– mice, and a relocalization of Bcl-2, which may indicate an apoptotic condition in the cell leading to the earlier reported pathological events, such as cardiomyocytes degeneration and calcinosis of the heart (Thornell et al., 1997).