M. Lambertz

Reticular formation of the lower brainstem. A common system for cardiorespiratory and somatomotor functions: discharge patterns of neighboring neurons influenced by cardiovascular and respiratory afferents☆

Experiments were done in dogs with chloralose-urethane anesthesia. Long-lasting extracellular recordings were made from the medial parts of the reticular formation of the lower brainstem for up to 250 min. The study is based on reactions of 103 neurons. The activities of 2 or 3 neighbouring neurons recorded under identical conditions with one electrode or of neurons recorded with two electrodes at the same time could be changed regularly and synchronously by experimental changes of hemodynamic or ventilatory parameters. Action potentials were separated by amplitude discrimination. Rhythmic pulsatile modulations were proved to be present in 78% of all neurons by post-event-time histograms triggered by the R-wave of the ECG. In the 96 neurons tested 86% changed their activity when arterial pressure was raised by inflating a balloon in the abdominal aorta (79% decreased and 7% increased their activity). In post-event-time histograms triggered by the start of inspiration, 83% of the neurons showed modulations of their activity with respiratory rhythm. Experimental lung inflation decreased the activity in 75% of the tested neurons, while experimental lung deflation activated 47% of the tested neurons. Stimulation of arterial chemoreceptors activated 77% of the tested neurons. It was thus demonstrated that receptors in the cardiovascular and respiratory systems exert an influence on nearly all neurons from which recordings were made in that part of the reticular formation. Arterial baroreceptors and lung stretch receptors revealed a generalized depressing effect on the neuronal activity while chemoreceptors exert a generalized augmenting effect. At different times of recording these neurons did not always react to the same extent to comparable stimulations of afferents.

Phase transitions in the common brainstem and related systems investigated by nonstationary time series analysis.

Neuronal activities of the reticular formation (RF) of the lower brainstem and the nucleus tractus solitarii (NTS, first relay station of baroreceptor afferents) were recorded together in the anesthized dog with related parameters of EEG, respiration and cardiovascular system. The RF neurons are part of the common brainstem system (CBS) which participates in regulation and coordination of cardiovascular, respiratory, somatomotor systems, and vigilance. Multiple time series of these physiological subsystems yield useful information about internal dynamic coordination of the organism. Essential problems are nonlinearity and instationarity of the signals, due to the dynamic complexity of the systems. Several time-resolving methods are presented to describe nonlinear dynamic couplings in the time course, particularly during phase transitions. The methods are applied to the recorded signals representing the complex couplings of the physiological subsystems. Phase transitions in these systems are detected by recurrence plots of the instationary signals. The pointwise transinformation and the pointwise conditional coupling divergence are measures of the mutual interaction of the subsystems in the state space. If the signals show marked rhythms, instantaneous frequencies and their shiftings are demonstrated by time frequency distributions, and instantaneous phase differences show couplings of oscillating subsystems. Transient signal components are reconstructed by wavelet packet time selective transient reconstruction. These methods are useful means for analyzing coupling characteristics of the complex physiological system, and detailed analyses of internal dynamic coordination of subsystems become possible. During phase transitions of the functional organization (a) the rhythms of the central neuronal activities and the peripheral systems are altered, (b) changes in the coupling between CBS neurons and cardiovascular signals, respiration and the EEG, and (c) between NTS neurons (influenced by baroreceptor afferents) and CBS neurons occur, and (d) the processing of baroreceptor input at the NTS neurons changes. The results of this complex analysis, which could not be done formerly in this manner, confirm and complete former investigations on the dynamic organization of the CBS with its changing relations to peripheral and other central nervous subsystems.

Reticular formation of the lower brainstem. A common system for cardiorespiratory and somatomotor functions: Discharge patterns of neighboring neurons influenced by somatosensory afferents☆

Extracellular recordings were made from 103 neurons located in the medial parts of the reticular formation of the lower brainstem of chloralose-urethane anesthetized dogs. Activities of 2 or 3 neighbouring neurons under identical conditions could be recorded with one electrode. In 9 recordings it was possible to register simultaneously up to 5 neurons with two electrodes placed in both halves of the medulla. Action potentials of individual neighbouring neurons were identified by amplitude discrimination. The influences of somatosensory afferents from skin, joints and muscles on neuronal discharge patterns were tested. Responses of single neurons were characterized by multisensory afferent spectra including afferents from various parts of the body. The combinations of afferents converging onto neighbouring neurons were similar, whereas neurons in more distant parts of the medulla revealed different combinations of converging afferents. In long-lasting recordings the influence of somatosensory afferents on the discharge behaviour changed from time to time. When the discharge behaviour was mainly determined by somatosensory afferents, neighbouring neurons were shown to be organized in sub-populations. The results led to the conclusion that in this part of the reticular formation different types of functional organization of the neuronal network are possible. The type of functional organization depends on the actual preponderances of different inputs to the neurons.

Dynamic Characteristics of the “Unspecific Brain Stem System”

The reticular formation of the lower brain stem is a morphological substrate for different functional systems.

Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Cross-correlation analysis of discharge patterns of neighbouring neurones

Temporal relations of discharges of 73 pairs of neurones located in the medial parts of the reticular formation of the lower brainstem were studied by cross correlation analyses in chloralose-urethane anaesthetized dogs. The action potentials of 2 or 3 neighbouring neurones were recorded with one electrode simultaneously. Uncorrelated discharges of neurones and 4 different types of correlated discharges were observed in cross correlation histograms: they were: (1) rhythmic couplings with frequencies between 2 and 5 Hz related to the same rhythm in the EEG; (2) strong, non-rhythmic couplings with short latencies up to 5 ms; (3) a combination of strong and rhythmic couplings, and (4) high-frequency oscillation couplings. Most pairs of neurones showed different types of correlation during the recordings. The different forms of correlated discharge behaviour could be related to different types of functional organization of the neuronal network in the reticular formation.

Central control and interactions affecting sympathetic and parasympathetic activity

Current thinking concerning the central control of the autonomic nervous system and the central interactions affecting sympathetic and parasympathetic activity is presented. Among the questions discussed are the following: are there neurons within the common brain stem system which exert an influence on preganglionic parasympathetic neurons and can they be differentiated from neurons which affect sympathetic preganglionic neuron functions? What interactions occur between sympathetic and parasympathetic tone-mediating neurons? In discussing these problems information is presented as obtained by recording from reticular formation (RF) neurons with discharge patterns similar to efferent parasympathetic activity. The general conclusion reached is that there is a common central control; interactions occur in the brain stem as well as peripherally; depending on the functional situation, these two systems can be organized to act either reciprocally or non-reciprocally.

Different modes of dampening influence from baroreceptors are determined by the functional organization of the NTS neuronal network.

Simultaneous recordings of several neurones of the first relay station of baroreceptor afferents show that its general activity-dampening influence is realized via the common brainstem system (CBS) which itself controls the processing on the neurones of the nucleus of the solitary tract (NTS). This feedback system maintains the degree of activity which is necessary for the ongoing behaviour as long as it fits to the environmental situation. The output of the NTS is determined partly by the CBS, partly by the properties of the peripheral afferent input, partly by the dynamic functional organization of the local circuits and partly by influences from other brain areas.

Nonstationary time-series analysis applied to investigation of brainstem system dynamics

Previous investigations of the dynamic organization of the lower brainstem and its relation to peripheral and other central nervous systems were predominantly performed by linear methods. These are based on time-averaging algorithms, which merely can be applied to stationary signal intervals. Thus, the current concept of the common brainstem system (CBS) in the reticular formation (RF) of the lower brainstem and basic types of its functional organization have been developed. Here, the authors present experiments where neuronal activities of the RF and the nucleus tractus solitarii (NTS, first relay station of baroreceptor afferents) were recorded together with related parameters of electroencephalogram (EEG), respiration, and cardiovascular system. The RF neurons are part of the CBS, which participates in regulation and coordination of cardiovascular, respiratory, and motor systems, and vigilance. The physiological time series, thus acquired, yield information about the internal dynamic coordination of the participating regulation processes. The major problem in evaluating these data is the nonlinearity and nonstationarity of the signals. The authors used a set of especially designed time resolving methods to evaluate nonlinear dynamic couplings in the interaction between CBS neurons and cardiovascular signals, respiration and the EEG, and between NTS neurons (influenced by baroreceptor afferents) and CBS neurons.

Integrative Control Mechanisms for Cardiorespiratory and Somatomotor Functions in the Reticular Formation of the Lower Brain Stem

From the functional point of view it is well accepted that only close interactions between cardiorespiratory and somatomotor control systems guarantee the integrity of organisms in all conditions of everyday life [30,31,83]. Characteristic modes of coordinations of somatomotor and autonomic innervation patterns determine the actual behavior. Both components of behaviorsomatomotor and autonomic — are not merely running parallel, but depend on each other. Adequate autonomic innervation enables the organism to realize somatomotor activity. On the other hand, the somatomotor nervous system assists the autonomic nervous system in homeostatic regulation. The functional synergy of the autonomic and the somatomotor nervous system was distinctly elaborated by W. R. Hess and by W. B. Cannon [15,30,31]. W. R. Hess discerned two functional states: an ergotropic one in which the autonomic nervous system supports the somatomotor system during intensive physical work and a trophotropic one in which the somatomotor system supports the autonomic nervous system in regulating assimilation and restitution of cell energy. This requires nervous structures responsible for integration of somatomotor and autonomic nervous activity.

Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Considerations aided by computer simulations

Parallel investigations were done using the reticular formation of the lower brainstem of dogs and computer simulated neuronal networks with properties of reticular neurones. By the aid of the simulations, understanding of the functional organisation of the common brainstem system, reticular formation and the experiments performed were optimized. The fact that discharge sequences of model neurones are very similar to those of reticular neurones was proved by interval histograms and covariance histograms. Discharges of neighbouring reticular neurones tend to be strongly coupled. In the model the discharges of the neurones could be coupled by common afferent inflows. Physiologically, neighbouring reticular neurones receive common afferents from peripheral somato-sensory systems. Neighbouring neurones with strongly coupled discharging are organized in subpopulations. The configurations of the subpopulations are determined by number and type of afferents actively influencing neurones and by the level of intrinsic activity of the network. Signal processing and transfer by neuronal subpopulations depend on the level of activity and on the degree of coupled discharging, i.e. the local organisation of the neurones.