Effect of change in levels of motor activity and innervation on basic and secondary rhythms of rat heart rate and respiration in ontogenesis

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneos motor activity were studied on offspring of white rats from newborn to 3-week age at transition from the state of active wakefulness to narcosis as well as under conditions of blockade of M-cholinoreceptors with atropine. It is shown that the endogenous rhythmical activity can be regulated not only by a change in frequency of basic rhythms, but also by action on all parameters and properties of their rhythmical variations and secondary rhythms. The changes in power of the heart secondary rhythms exceed considerably the frequency oscillations of basic rhythms during blockade of cholinergic innervation or a change in the motor activity level that affects both the basic rhythm circulation and respiration and their variations--secondary rhythms. The atropine blockade of M-cholinoreceptors at the studied ages changes the heart beating rhythm within the limits of 10% of bradicardia in newborns to tachycardia in the 3-week old animals. At the same time, power of the cardiac rhythm secondary oscillations changes several times. These data indicate that the cholinergic mechanisms play the key role in formation of the secondary rhythms and their correlation with motor activity.     

Secondary rhythms of automatically functioning systems

In wakeful rats at the age from newborn to 3 weeks there were studied interrelations of rhythmical oscillations of heart rate, respiration rate, and periodic spontaneous motor activity. In all studied systems, these oscillations are coordinated and occur in several frequency diapasons. Frequencies in the near-minute diapason (the period from 30 to 90 s) are the most constant and do not change with age. Regular oscillations are the most stable in newborns. Bursts of motor activity usually are irregular, but episodically the distinct near-minute rhythm is traced. Studies of the character of interaction of the heart activity, respiration, and periodic somatomotor excitation allow stating that the main coordination pathway of spontaneous autorhythmic functions in early postnatal ontogenesis is formation of secondary rhythms. Possible ways of formation of the secondary rhythms are considered.     

Structure of autorhythmical activity of contractile systems

In the autorhythmical activity underlying many visceral and in early ontogenesis also somatomotor systems, three kinds of rhythms are to be distinguished: basic, reflecting activity of individual organs and of systems of organs, the secondary ones representing result of the frequency and amplitude modulation of the basic rhythms, and the rhythmical periodic activity whose distinguishing feature is alternation of the activity and rest phases. Each kind has principally different frequency characteristics, different organization and localization of sources. The frequency of basic rhythms is determined by the generator inserted into the system. It serves an individual characteristics of the current state of function of the organ, the degree of maturity of its motor apparatus. The secondary rhythm and the rhythm of the periodic activity cycles are provided by oscillatory processes common to the whole organism. Universality of these rhythms promotes integration of functions.     

Role of sympathetic and parasympathetic mechanisms in formation of secondary cardiac rhythms in rats ontogenesis

In progeny of Wistar rats aged from birth to 3 week, there was studied participation of sympathetic and parasympathetic mechanisms in regulation of cardiac rhythm and its rhythmic oscillations (secondary cardiac rhythms), whose spectral composition was analyzed using rapid Fourier transformation. Consequences, which changed in the process of development, of blockade of -adrenoreceptors by propranolol, of -adrenoreceptors by phentolamine, and of muscarinic cholinoreceptors by atropine as well as of chronic desympathization by guanethidine (isobarine). It was found that due to heterochronia in establishment of functions of sympathetic and parasympathetic nervous systems, reactions to blockade of adreno- and cholinoreceptors for the first 3 weeks of postnatal ontogenesis changed not only quantitatively, but also qualitatively. Blockade of adrenoreceptors in newborn animals leads to an increase of power of the rhythm oscillations in all low-frequency diapasons. The baroreflex function of parasympathetic innervation is well expressed as early as in newborns. Tonic function with respect to frequency of heart rate and power of oscillations in the high-frequency diapason becomes evident only by the 3-week age.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 69–75.Original Russian Text Copyright © 2005 by Bursian, Sizonov, Semenova, Kulaev, Timofeeva, Polyakova, Dmitrieva.     

Quantitative estimation of connection of the heart rate rhythm with motor activity in rat fetuses

In rat fetuses over E17-20 with preserved placental circulation with use of mathematical analysis there were revealed value and character of connections of slow wave oscillations of the heart rhythm with motor activity for 30 min of observation. In the software PowerGraph 3.3.8, normalization and filtration of the studied signals were performed in three frequency diapasons: D1-0.02–0.2 Hz (5–50 s), D2-0.0083-0.02 Hz (50 s-2 min), and D3-0.0017–0.0083 Hz (2–10 min). The EMG curves filtrated by diapasons or piezograms were compared with periodograms in the corresponding diapasons of the heart rhythm variations. In the software “Origin 8.0”, quantitative estimation of the degree of intersystemic interrelations for each frequency diapason was performed by Pearson correlation of coefficient, by the correlation connection value, and by the time shift of maximum of cross-correlation function. It has been established that in the frequency D1, regardless of age, the connection of heart rhythm oscillations with motor activity is expressed weakly. In the frequency diapason D2, the connection in most cases is located in the zone of weak and moderate correlations. In the multiminute diapason (D3), the connection is more pronounced. The number of animals that have a significant value of the correlation connection rises. The fetal motor activity fires in the decasecond diapason in all age groups are accompanied by short-time decelerations of the heart rhythms. In the minute diapason, there is observed a transition from positive connections in E17 and E18 to the negative ones in E19-20. Results of the study are considered in association with age-related changes of ratios of positive and negative oscillations of the heart rhythm change depending on the character of motor activity.     

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.     

Interaction between dopaminergic and cholinergic systems under conditions of deficiency of mesencephalo-striatal dopamine in rats

In chronic behavioral experiments on rats with a unilateral deficiency of mesencephalo-striatal dopamine, we studied the effect of the blocker of M-cholinoreceptors atropine on the rotational motor activity induced by systemic injections of dopamine agonists exerting direct (apomorphine) and indirect (amphetamine) actions. We found that premedication with atropine increased significantly the intensity of the rotational movements induced by both apomorphine and amphetamine. We conclude that the mesencephalo-striatal dopaminergic system exerts inhibitory effects on cholinergic neurons of the neostriatum. Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 459–462, September–December, 2005.     

Relationship between cortical electrical and cardiac autonomic activities in the awake lizard, Gallotia galloti

ECG and EEG signals were simultaneously recorded in lizards, Gallotia galloti, both in control conditions and under autonomic nervous system (ANS) blockade, in order to evaluate possible relationships between the ANS control of heart rate and the integrated central nervous system activity in reptiles. The ANS blockers used were prazosin, propranolol, and atropine. Time-domain summary statistics were derived from the series of consecutive R-R intervals (RRI) of the ECG to measure beat-to-beat heart rate variability (HRV), and spectral analysis techniques were applied to the EEG activity to assess its frequency content. Both prazosin and atropine did not alter the power spectral density (PSD) of the EEG low frequency (LF: 0.5-7.5 Hz) and high frequency (HF: 7.6-30 Hz) bands, whereas propranolol decreased the PSD in these bands. These findings suggest that central beta-adrenergic receptor mechanisms could mediate the reptilian waking EEG activity without taking part any alpha(1)-adrenergic and/or cholinergic receptor systems. In 55% of the lizards in control conditions, and in approximately 43% of the lizards under prazosin and atropine, a negative correlation between the coefficient of variation of the series of RRI value (CV(RRI)) and the mean power frequency (MPF) of the EEG spectra was found, but not under propranolol. Consequently, the lizards' HRV-EEG-activity relationship appears to be independent of alpha(1)-adrenergic and cholinergic receptor systems and mediated by beta-adrenergic receptor mechanisms.     

Rhythmic modulation of theta oscillations supports encoding of spatial and behavioral information in the rat hippocampus

Oscillatory patterns of activity in various frequency ranges are ubiquitously expressed in cortical circuits. While recent studies in humans emphasized rhythmic modulations of neuronal oscillations ("second-order" rhythms), their potential involvement in information coding remains an open question. Here, we show that a rhythmic (～0.7?Hz) modulation of hippocampal theta power, unraveled by second-order spectral analysis, supports encoding of spatial and behavioral information. The phase preference of neuronal discharge within this slow rhythm significantly increases the amount of information carried by action potentials in various motor/cognitive behaviors by (1) distinguishing between the spikes fired within versus outside the place field of hippocampal place cells, (2) disambiguating place firing of neurons having multiple place fields, and (3) predicting between alternative future spatial trajectories. This finding demonstrates the relevance of second-order spectral components of brain rhythms for decoding neuronal information.     

Oscillations in calcium-cyclic AMP control loops form the basis of pacemaker activity and other high frequency biological rhythms.

In this paper theoretical and experimental evidence is presented which indicates that oscillations in internal calcium and cyclic AMP concentrations due to an instability in their common control loops are possible and indeed may be widespread. Further, it is demonstrated that fluctuations in various cellular properties, in particular membrane potential, are a direct consequence of these second messenger oscillations. Given the central importance of calcium and cyclic AMP to the regulation of metabolism, these oscillations would influence most metabolic processes especially rhythmic behaviour. We propose that these oscillations form the basis of several biological rhythms including, potential oscillations in cardiac pacemaker cells, neurones and insulin secreting β-cells, the minute rhythm in smooth muscle, cyclic AMP pulses in Dictyostelium, rhythmical cytoplasmic streaming in Physarum and transepitheliel potential oscillations in Calliphora salivary gland. This model makes possible an explanation of the frequency and amplitude effects of hormones.     

Organization of endogenous rhythms of motor functions (To the 100-Anniversary of A.V. Voino-Yasenetskii)

Two categories of endogenous rhythmical activity of somatic and visceral muscle are considered: the basic rhythms determined by morphofunctional and age-related characteristics of an organ or system and the secondary rhythms characterized by wide spreading in different systems, age-related stability, and many-level organization. In early ontogenesis, both forms of rhythmical activity has the common goal—to provide homeostasis of the growing organism under conditions of limited external afferentation and imperfection of adaptive regulatory mechanisms. Formation of the secondary rhythms is considered as the way and the result of coordination of functions that have endogenous rhythmicity.     

Capsaicin increases modulation of sympathetic nerve activity in rats: measurement using power spectral analysis of heart rate fluctuations

We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.     

Different origins of gamma rhythm and high-gamma activity in macaque visual cortex

During cognitive tasks electrical activity in the brain shows changes in power in specific frequency ranges, such as the alpha (8-12 Hz) or gamma (30-80 Hz) bands, as well as in a broad range above ～80 Hz, called the high-gamma band. The role or significance of this broadband high-gamma activity is unclear. One hypothesis states that high-gamma oscillations serve just like gamma oscillations, operating at a higher frequency and consequently at a faster timescale. Another hypothesis states that high-gamma power is related to spiking activity. Because gamma power and spiking activity tend to co-vary during most stimulus manipulations (such as contrast modulations) or cognitive tasks (such as attentional modulation), it is difficult to dissociate these two hypotheses. We studied the relationship between high-gamma power, gamma rhythm, and spiking activity in the primary visual cortex (V1) of awake monkeys while varying the stimulus size, which increased the gamma power but decreased the firing rate, permitting a dissociation. We found that gamma power became anti-correlated with the high-gamma power, suggesting that the two phenomena are distinct and have different origins. On the other hand, high-gamma power remained tightly correlated with spiking activity under a wide range of stimulus manipulations. We studied this relationship using a signal processing technique called Matching Pursuit and found that action potentials are associated with sharp transients in the LFP with broadband power, which is visible at frequencies as low as ～50 Hz. These results distinguish broadband high-gamma activity from gamma rhythms as an easily obtained and reliable electrophysiological index of neuronal firing near the microelectrode. Further, they highlight the importance of making a careful dissociation between gamma rhythms and spike-related transients that could be incorrectly decomposed as rhythms using traditional signal processing methods.     

Capsaicin Increases Modulation of Sympathetic Nerve Activity in Rats: Measurement Using Power Spectral Analysis of Heart Rate Fluctuations

We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz<, HF) and low (LF, <1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.     

Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)

On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the inter-systemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and manyminute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason—are weakly enhanced.     

Secondary Rhythms of Cardiac Activity within Early Ontogenesis: Effects of Blocking of Adreno- and Cholinoreceptors in Rats

The genesis of secondary rhythms in autorhythmic functional systems is analyzed on the example of the spectra of fluctuations of the heart rate observed within early postnatal ontogenesis of rats (from the moment of birth until three weeks old). We studied the effects of blocking of -adrenoreceptors with phentolamine (5 mg/kg, i.p.), of -adrenoreceptors with propranolol (1 mg/kg), and of M cholinoreceptors with atropine (1 mg/kg). We concluded that sympathetic influences stabilize the cardiac rhythm in newborn animals, but from the second postnatal week the effects determining generation of secondary rhythms of cardiac activity begin to be mediated by these receptors. Parasympathetic effects on secondary cardiorhythms mediated by M cholinoreceptors are effective even in newborn rats. In rats older than 7 to 8 days, blocking of -adrenoreceptors and M cholinoreceptors led to the same result, synchronization of the secondary cardiac rhythms. Disorders in the afferent link of the baroreflex arcs after the blockade of -adrenoreceptors and cessation of transmission in the efferent link of these arcs after blockade of M cholinoreceptors are considered a probable reason for this phenomenon.     

Effect of change in activity level of catecholaminergic systems on motor, respiratory, and cardiac activities in rat embryos

Parameters of motor, respiratory and cardiac activities were studied in rat embryos (E17-20) after changes in activity level of catecholaminergic systems. To produce conditions for excessive level of catecholamines, the animal were administered individually with preparation of L-DOPA at doses of 25, 50 and 100 mg/kg. Also studied was action of L-DOPA after blockade of D1-(antagonist - SCH-23390, 0.1 mg/kg), D2-(antagonist - sulpiride, 50 mg/kg) dopaminic, and beta2-(antagonist - propranolol, 1 mg/kg) adrenergic receptors. It was found out in E17-18 that the DOPA administration regardless of dose, while in E19-20 dose-dependently produces continuous generalized activity. Between E18 and E19, ontogenetically new is the appearance in 92 % of embryos of stereotypical head movements (circular movements, lateral and dorso-ventral flexions) following in the nearsecond rhythm. Injection of DOPA to rat embryos increased 2-6 times the number of respiratory movements by the gasping type in E17-20 and decreased the amount of episodes of continuous rhythmical respiration in E19-20. No significant heart rate changes were observed after introduction of DOPA to E17-20. There was noted a tendency for a weak acceleration of the heart rate. The changes in activities of the motor and respiratory systems due to a rise of catecholamine level are not connected with activation of the dopamine system, as they are not reduced by blockade of dopamine receptors.     

Intrinsic and extrinsic influences on cardiac rhythms in crustaceans

Several factors cause predictable changes in heart rate of crustaceans thus affecting basic heart rhythms. In decapod crustaceans these consist of: many internal factors including influences from neural and neurohormonal systems and chemosensory influences; many external factors including startling stimuli and other disturbance; ventilatory (scaphognathite) reversals; tail flips and other postural movements including locomotor activity; and variations in environmental factors such as oxygen level, temperature and air-exposure. In many cases the initial response involves temporary bradycardia or cardiac arrest. These responses may quickly facilitate to sustained low level stimuli although maintained strong stimulation will eventually be associated with cardio-acceleration and escape responses. Measurement of change in heart rate alone is rarely a sensible monitor of cardiac performance in crustaceans since simultaneous changes in cardiac stroke volume occur which may confound diagnosis. Hypoxia for instance causes decrease in heart rate of adult crustaceans but the apparent decrease in cardiac output is offset or reversed by increase in stroke volume. Concomitant changes occur in cardiac output and in the proportion of cardiac output which is delivered to particular tissues. In fact change in heart rhythm is only one factor in a complex suite of responses involving several physiological systems which compensate uniquely for changes in environmental or other stimuli. Both neural and neuro-hormonal factors are known to play a role in control of these complex responses.     

Effect of change in activity level of catecholaminergic systems on motor,respiratory, and cardiac activities in fetal rats

Parameters of motor, respiratory, and cardiac activities were studied in rat embryos (E17–20) after changes in activity level of catecholaminergic systems. To conditions for excessive level of catecholamines, the animals were administered individually with L-DOPA at doses of 25, 50, and 100 mg/kg. Also studied was action of L-DOPA after blockade of D1-(antagonist—CHS-23390, 0.1 mg/kg), D2-(antagonist—sulpiride, 50 mg/kg) dopaminic, and β₂-(antagonist—propranolol, 1 mg/kg) adrenergic receptors. It was found in E17–18 that the DOPA administration regardless dose, while in E19–20 dose-dependently produces continuous generalized activity. Between E18 and E19, ontogenetically novel is the appearance in 92% of embryos of stereotypical head movements (circular movements, lateral and dorsoventral flexions) following in the near-second rhythm. Injection of DOPA to rat embryos increased 2–6 times the number of respiratory movements of the gasping time in E17–20 and decreased the amount of episodes of continuous rhythmical respiration in E19–20. No significant heart rate changes were observed after introduction of DOPA to E17–20. There was noted a tendency for a weak acceleration of the heart rate. The changes in activities of the motor and respiratory systems due to a rise of catecholamine level are not connected with activation of the dopamine system, as they are not reduced by blockade of dopamine receptors.