Biomedical subjects

L S Segers

Publications and source records attributed to L S Segers.

6 recordsLinked to original sources

PubMed2000

Respiratory neuronal assemblies.

This review describes results from in vivo experiments on brain stem network mechanisms that control breathing. Multi-array recording technology and computational methods were used to test predictions derived from simulations of respiratory network models. This highly efficient approach has the advantage that many simultaneously recorded neurons are subject to shared stimulus, history, and state-dependent conditions. Our results have provided evidence for concurrent or parallel network interactions in the generation and modulation of the respiratory motor pattern. Recent data suggest that baroreceptors, chemoreceptors, nociceptors, and airway cough receptors shape the respiratory motor pattern, at least in part, through a system of shared coordinated 'multifunctional' neurons distributed in the brain stem. The 'gravity method' for the analysis and representation of multi-neuron data has demonstrated respiratory phase-dependent impulse synchrony among neurons with no respiratory modulation of their individual firing rates. The detection of this emergent property motivated the development of pattern detection methods that subsequently identified repeated transient configurations of these 'correlational assemblies'. These results support the view that information can be 'coded' in the nervous system by spike timing relationships, in addition to firing rate changes that traditionally have been measured by neurophysiologists.

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PubMed1994

Distributed actions and dynamic associations in respiratory-related neuronal assemblies of the ventrolateral medulla and brain stem midline: evidence from spike train analysis.

1. Considerable evidence indicates that neurons in the brain stem midline and ventrolateral medulla participate in the control of breathing. This work was undertaken to detect and evaluate evidence for functional links that coordinate the parallel operations of neurons distributed in these two domains. 2. Data were from 51 Dial-urethan-anesthetized, bilaterally vagotomized, paralyzed, artificially ventilated cats. Planar arrays of tungsten microelectrodes were used to monitor simultaneously spike trains in two or three of the following regions: n. raphe obscurus-n. raphe pallidus, n. raphe magnus, rostral ventrolateral medulla, and caudal ventrolateral medulla. Efferent phrenic nerve activity was recorded to indicate the phases of the respiratory cycle. Electrodes in the ventral spinal cord (C3) were used in antidromic stimulation tests for spinal projections of neurons. 3. Spike trains of 1,243 neurons were tested for respiratory modulated firing rates with cycle-triggered histograms and an analysis of variance with the use of a subjects-by-treatments experimental design. Functional associations were detected and evaluated with cross-correlograms, snowflakes, and the gravity method. 4. Each of 2,310 pairs of neurons studied included one neuron monitored within 0.6 nm of the brain stem midline and a second cell recorded in the ventrolateral medulla; 117 of these pairs (5%) included a neuron with a spinal projection, identified with antidromic stimulation methods, that extended to at least the third cervical segment. Short-time scale correlations were detected in 110 (4.7%) pairs of neurons. Primary cross-correlogram features included 40 central peaks, 47 offset peaks, 4 central troughs, and 19 offset troughs. 5. In 14 data sets, multiple short-time scale correlations were found among three or more simultaneously recorded neurons distributed between both midline and ventrolateral domains. The results suggested that elements of up to three layers of interneurons were monitored simultaneously. Evidence for concurrent serial and parallel regulation of impulse synchrony was detected. Gravitational representations demonstrated respiratory-phase dependent synchrony among neurons distributed in both brain stem regions. 6. The results support a model of the brain stem respiratory network composed of coordinated distributed subassemblies and provide evidence for several hypotheses. 1) Copies of respiratory drive information from rostral ventrolateral medullary (RVLM) respiratory neurons are transmitted to midline neurons. 2) Midline neurons act on respiratory-related neurons in the RVLM to modulate phase timing. 3) Impulse synchrony of midline neurons is influenced by concurrent divergent actions of both midline and ventrolateral neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1989

Discharge patterns of rostrolateral medullary expiratory neurons in the cat: regulation by concurrent network processes.

1. The identification of numerous functional connections among medullary respiratory related neurons led us to postulate specific short time scale correlations among neuronal spike trains consistent with 1) inhibition of rostrolateral medullary augmenting expiratory (E-AUG) neurons by other E-AUG cells, and 2) inhibitory control of the postulated E-AUG neural network by decrementing expiratory (E-DEC) neurons. Recent observations of reduced rostrolateral E-AUG cell activity following stimulation of sensory afferents raised the additional question of whether reflex control mechanisms use the identified functional connections to mediate their effects. 2. Experiments were conducted on 42 anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Impulse trains of two or more respiratory related neurons of the lateral medulla, including at least one rostrolateral medullary E-AUG neuron, were simultaneously recorded together with phrenic nerve efferent activity. Most neurons were tested for spinal axonal projections with antidromic stimulation methods. In some experiments, the central cut end of the right vagus nerve was electrically stimulated during the expiratory interval. Data were analyzed using cycle-triggered histograms, auto- and cross-correlograms, logical cross-correlograms, snowflake scatter diagrams, and peristimulus time histograms. 3. Seven of 73 pairs (9.6%) of ipsilateral E-AUG neurons exhibited short time scale correlations in firing probability. Two rostral pairs had coincident increases in activity. Five pairs were characterized by a reduction in activity in a rostral neuron following spikes in the other cell; concurrent serial inhibition among one set of three E-AUG neurons was indicated. These five pairs, together with three other similarly correlated pairs described previously, were studied further: spikes recorded during the first and second halves of the expiratory (E) phase were analyzed separately. This phase segmentation unmasked multiple correlations implying reciprocal inhibition between one pair of E-AUG neurons. Short time scale troughs in correlograms generated from late E-phase spike trains had significantly (P less than 0.05) greater detectability indices than troughs in early E-phase correlograms. Multineuron correlations revealed two cases in which the firing probability of the target E-AUG neuron was reduced less when only reference E-AUG cell spikes coincident with spikes in a third, E-DEC, neuron were used as trigger events. 4. Enhanced rostral E-AUG neuron firing probabilities coincident with or following impulses in ipsilateral E-DEC neurons were detected in 6 of 94 (6.4%) rostral pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1987

Functional associations among simultaneously monitored lateral medullary respiratory neurons in the cat. I. Evidence for excitatory and inhibitory actions of inspiratory neurons.

Data were obtained from 45 anesthetized (Dial), paralyzed, artificially ventilated, bilaterally vagotomized cats. Arrays of extracellular electrodes were used to monitor simultaneously the activities of lateral medullary respiratory neurons located in the rostral and caudal regions of the ventral respiratory group. The average discharge rate as a function of time in the respiratory cycle was determined for each neuron and concurrent phrenic nerve activity. Most cells were tested for axonal projections to the spinal cord or the ipsilateral vagus nerve using antidromic stimulation techniques. Seven hundred and sixty-one pairs of ipsilateral respiratory neurons that contained at least one neuron whose maximum discharge rate occurred during the inspiratory phase were analyzed by cross-correlation of the simultaneously recorded spike trains. Twenty-three percent of the 410 pairs of inspiratory (I) neurons showed short time scale correlations indicative of functional association due to paucisynaptic connections or shared inputs. Eight per cent of the 351 pairs composed of an I cell and and expiratory (E) neuron were correlated. We found evidence for excitation of both bulbospinal I neurons and I cells that were not antidromically activated by stimulation of the spinal cord and vagus nerve (NAA neurons) by NAA I cells. We also obtained data suggesting inhibitory actions of cells whose maximum discharge rate occurred in the first half of the I phase (I-DEC neurons). These actions included inhibition of other I-DEC neurons, inhibition of cells whose greatest firing rate occurred in the last half of the I phase (I-AUG neurons), inhibition of E-DEC neurons, and inhibition of E-AUG cells. Sixty-two percent (31/50) of the correlations that could be interpreted as evidence for an excitatory or inhibitory paucisynaptic connection were detected in pairs composed of a caudal and a rostral ventral respiratory group neuron. Eighty-eight percent (14/16) of proposed intergroup excitatory connections involved a projection from the rostral neuron of the pair to the caudal cell, whereas 73% (11/15) of proposed inhibitory connections involved a caudal-to-rostral projection. These results support and suggest several hypotheses for mechanisms that may help to control the development of augmenting activity in and the timing of each phase of the respiratory cycle.

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PubMed1987

Functional associations among simultaneously monitored lateral medullary respiratory neurons in the cat. II. Evidence for inhibitory actions of expiratory neurons.

Arrays of extracellular electrodes were used to monitor simultaneously several (2-8) respiratory neurons in the lateral medulla of anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Efferent phrenic nerve activity was also recorded. The average discharge rate as a function of time in the respiratory cycle was determined for each neuron. Most cells were tested for spinal or vagal axonal projections using antidromic stimulation methods. Cross-correlational methods were used to analyze spike trains of 480 cell pairs. Each pair included at least one neuron most active during the expiratory phase. All simultaneously recorded neurons were located in the same side of the brain stem. Twenty-six percent (33/129) of the expiratory (E) neuron pairs exhibited short time scale correlations indicative of paucisynaptic interactions or shared inputs, whereas 8% (27/351) of the pairs consisting of an E neuron and an inspiratory (I) cell were similarly correlated. Evidence for several inhibitory actions of E neurons was found: 1) inhibition of I neurons by E neurons with both decrementing (DEC) and augmenting (AUG) firing patterns; 2) inhibition of E-DEC and E-AUG neurons by E-DEC cells; 3) inhibition of E-DEC and E-AUG neurons by E-AUG neurons; and 4) inhibition of E-DEC neurons by tonic I-E phase-spanning cells. Because several cells were recorded simultaneously, direct evidence for concurrent parallel and serial inhibitory processes was also obtained. The results suggest and support several hypotheses for mechanisms that may help to generate and control the pattern and coordination of respiratory motoneuron activities.

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PubMed1985

Interactions between rostral pontine and ventral medullary respiratory neurons.

Lesioning studies have demonstrated that the respiratory rhythm is generated within the brain stem and that connections between the pons and the medulla must be intact for the generation of eupneic breathing in the decerebrate or anesthetized vagotomized cat. However, the nature of proposed functional connections between pontine and medullary respiratory neurons is not well understood. The possibility of interactions between respiratory neurons of the rostral pons (n. parabrachialis medialis, Kölliker-Fuse nucleus) and the ipsilateral ventral respiratory group (VRG; n. retroambigualis, n. ambiguus, retrofacial nucleus) was investigated because of neuroanatomical and electrophysiological evidence for such connections. Phrenic nerve activity and pontine and medullary single-unit respiratory related activities were recorded extracellularly in 44 decerebrate, vagotomized, paralyzed, and artificially ventilated cats. Cross-correlation analysis was employed to detect and evaluate functional associations of pairs of cells. Eighteen (7%) of the 255 pairs of respiratory neurons analyzed showed evidence of short time scale correlations indicative of a functional interaction. The interpretations of the detected correlations suggest that some cell pairs were correlated due to mono- or paucisynaptic connections, while others were correlated due to the influence of an unobserved shared input. The interpretations for 11 of the 15 cell pairs for which a monosynaptic connection may be postulated involve a projection from a tonically active respiratory neuron. Twelve of the 18 positive correlations involved neurons whose maximum rates of discharge occurred during different parts of the respiratory cycle. The results of this study provide the first evidence of functional connections among pontine and medullary respiratory neurons based on the evaluation of simultaneously recorded spike trains and suggest that the role of the rostral pontine respiratory neurons in the control of the respiratory rhythm may be mediated by various types of interactions. When considered with the results of other studies, our data suggest that monosynaptic interactions between VRG and rostral pontine respiratory neurons play a limited role in the control of the respiratory cycle in the decerebrate vagotomized cat. It is likely that the influence of the pons on ventral medullary neurons (and vice-versa) is also exerted via polysynaptic pathways and/or via brain stem neurons not sampled in this study.

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