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B G Lindsey

Publications and source records attributed to B G Lindsey.

At least 19 recordsLinked to original sources
PubMed2003

Invited review: Neural network plasticity in respiratory control.

Respiratory network plasticity is a modification in respiratory control that persists longer than the stimuli that evoke it or that changes the behavior produced by the network. Different durations and patterns of hypoxia can induce different types of respiratory memories. Lateral pontine neurons are required for decreases in respiratory frequency that follow brief hypoxia. Changes in synchrony and firing rates of ventrolateral and midline medullary neurons may contribute to the long-term facilitation of breathing after brief intermittent hypoxia. Long-term changes in central respiratory motor control may occur after spinal cord injury, and the brain stem network implicated in the production of the respiratory rhythm could be reconfigured to produce the cough motor pattern. Preliminary analysis suggests that elements of brain stem respiratory neural networks respond differently to hypoxia and hypercapnia and interact with areas involved in cardiovascular control. Plasticity or alterations in these networks may contribute to the chronic upregulation of sympathetic nerve activity and hypertension in sleep apnea syndrome and may also be involved in sudden infant death syndrome.

Animals↗
PubMed2001

Medullary respiratory neurones and control of laryngeal motoneurones during fictive eupnoea and cough in the cat.

1. This study addressed the hypothesis that ventrolateral medullary respiratory neurones participate in the control of laryngeal motoneurones during both eupnoea and coughing. 2. Data were obtained from 28 mid-collicular decerebrated, artificially ventilated cats. Cough-like motor patterns (fictive cough) in phrenic, lumbar and recurrent laryngeal nerves were elicited by mechanical stimulation of the intrathoracic trachea. Microelectrode arrays were used to monitor simultaneously several neurones in the ventral respiratory group, including the Bötzinger and pre-Bötzinger complexes. Spike trains were evaluated for responses during fictive cough and evidence of functional connectivity with spike-triggered averages of efferent recurrent laryngeal nerve activity. 3. Primary features were observed in averages triggered by 94 of 332 (28 %) neurones. An offset biphasic wave with a positive time lag was present in the unrectified average for 10 inspiratory and 13 expiratory neurones. These trigger neurones were respectively identified as inspiratory laryngeal motoneurones with augmenting, decrementing, plateau and "other" discharge patterns, and expiratory laryngeal motoneurones with decrementing firing patterns. 4. Rectified averages triggered by inspiratory neurones included 37 offset peaks, 11 central peaks and one offset trough. Averages triggered by expiratory neurones had 12 offset peaks, six central peaks and four offset troughs. Relationships inferred from these features included premotor actions of inspiratory neurones with augmenting, decrementing, plateau and "other" patterns on inspiratory laryngeal motoneurones, and premotor actions of decrementing and "other" expiratory neurones on expiratory laryngeal motoneurones. Corresponding changes in neuronal firing patterns during fictive cough supported these inferences. 5. The data confirm and extend previous results on the control of laryngeal motoneurones during eupnoea and support the hypothesis that the same premotor neurones help to shape motoneurone firing patterns during both eupnoea and coughing.

Action Potentials↗
PubMed2001

Changes in cat medullary neurone firing rates and synchrony following induction of respiratory long-term facilitation.

1. Long-term facilitation is a respiratory memory expressed as an increase in motor output lasting more than an hour. This change is induced by repeated hypoxia, stimulation of carotid chemoreceptors, or electrical stimulation of the carotid sinus nerve or brainstem mid-line. The present work addressed the hypothesis that persistent changes in medullary respiratory neural networks contribute to long-term facilitation. 2. Carotid chemoreceptors were stimulated by close arterial injection of CO(2)-saturated saline solution. Phrenic nerve efferent activity and up to 30 single medullary neurones were recorded simultaneously in nucleus tractus solitarii (NTS) including the dorsal respiratory group (DRG), Botzinger-ventral respiratory group (Böt-VRG), and nucleus raphe obscurus of nine adult cats, anaesthetized, injected with a neuromuscular blocking agent, vagotomized and artificially ventilated. 3. The firing rates of 87 of 105 neurones (83 %) changed following induction of long-term facilitation. Nine of eleven DRG and Böt-VRG putative premotor inspiratory neurones had increased firing rates with long-term facilitation. Fourteen of twenty-one raphe obscurus neurones with control firing rates less than 4 Hz had significant long-term increases in activity. 4. Cross-correlogram analysis suggested that there were changes in effective connectivity of neuron pairs with long-term facilitation. Joint peristimulus time histograms and pattern detection methods used with 'gravity' analysis also detected changes in short time scale correlations associated with long-term facilitation. 5. The results suggest that changes in firing rates and synchrony of VRG and DRG premotor neurones and altered effective connectivity among other functionally antecedent elements of the medullary respiratory network contribute to the expression of long-term facilitation.

Action Potentials↗
PubMed2000

Transient configurations of baroresponsive respiratory-related brainstem neuronal assemblies in the cat.

The regulation of gas exchange requires coordination of the respiratory and cardiovascular systems. Previous work suggested that medullary raphe neurones transform and transmit information from baroreceptors to neurones in the ventral respiratory group. This study tested the hypothesis that distributed brainstem neuronal assemblies are transiently reconfigured during the respiratory cycle and baroreceptor stimulation. Blood pressure was perturbed by intravenous injection of an alpha1-adrenergic receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion of the descending aorta in 14 Dial-urethane anaesthetized, vagotomized, paralysed, artificially ventilated cats. Neurones were monitored simultaneously with microelectrode arrays in two or more of the following sites: n. raphe obscurus, n. raphe magnus, rostral and caudal ventrolateral medulla, and the nucleus tractus solitarii. Transient configurations of baroresponsive assemblies were detected with joint pericycle-triggered histograms, the gravitational representation, and related pattern detection methods. Data were also analysed with cycle-triggered histograms, peristimulus-time and cumulative sum histograms, cross-correlograms, spike-triggered averages of efferent phrenic activity, and joint impulse configuration scatter diagrams (snowflakes). Five to nine simultaneously recorded spike trains from control expiratory phases were compared with data from interleaved equal-duration time blocks from control inspiratory phases. In each of seven animals, significant impulse synchrony detected by gravity analysis was confined to one phase of the respiratory cycle. Repeated patterns of distributed synchrony confined to periods of altered baroreceptor activity were detected and involved neurones that individually did not change firing rates during stimulation. Snowflakes and logical cross-correlation analysis provided evidence for the cooperative actions of impulses in concurrently active parallel channels. In 12 of 17 pairs of neurones with at least one baroresponsive cell, joint pericycle-triggered histograms detected synchrony indicative of shared inputs or functional excitatory interactions that varied as a function of time in the respiratory cycle. Neurones in four of the pairs had no respiratory modulation of their individual firing rates. Data from eight other pairs were indicative of fluctuations in inhibition during the respiratory cycle. The results demonstrate repeated transient configurations of baroresponsive neuronal assemblies during the respiratory cycle, without concomitant firing rate changes in the constituent neurones, and suggest distributed network mechanisms for the modulation of baroreceptor-mediated reflexes.

Animals↗
PubMed2000

Functional connectivity among ventrolateral medullary respiratory neurones and responses during fictive cough in the cat.

This study tested predictions from a network model of ventrolateral medullary respiratory neurone interactions for the generation of the cough motor pattern observed in inspiratory and expiratory pump muscles. Data were from 34 mid-collicularly decerebrated, paralysed, artificially ventilated cats. Cough-like patterns (fictive cough) in efferent phrenic and lumbar nerve activities were elicited by mechanical stimulation of the intrathoracic trachea. Neurones in the ventral respiratory group, including the Botzinger and pre-Botzinger complexes, were monitored simultaneously with microelectrode arrays. Spike trains were analysed for evidence of functional connectivity and responses during fictive cough with cycle-triggered histograms, autocorrelograms, cross-correlograms, and spike-triggered averages of phrenic and recurrent laryngeal nerve activities. Significant cross-correlogram features were detected in 151 of 1988 pairs of respiratory modulated neurones. There were 59 central peaks, 5 central troughs, 11 offset peaks and 2 offset troughs among inspiratory neurone pairs. Among expiratory neurones there were 23 central peaks, 8 offset peaks and 4 offset troughs. Correlations between inspiratory and expiratory neurones included 20 central peaks, 10 central troughs and 9 offset troughs. Spike-triggered averages of phrenic motoneurone activity had 51 offset peaks and 5 offset troughs. The concurrent responses and multiple short time scale correlations support parallel and serial network interactions proposed in our model for the generation of the cough motor pattern in the respiratory pump muscles. Inferred associations included the following. (a) Excitation of augmenting inspiratory (I-Aug) neurones and phrenic motoneurones by I-Aug neurones. (b) Inhibition of augmenting expiratory (E-Aug) neurones by decrementing inspiratory (I-Dec) neurones. (c) Inhibition of I-Aug, I-Dec and E-Aug neurones by E-Dec neurones. (d) Inhibition of I-Aug and I-Dec neurones and phrenic motoneurones by E-Aug neurones. The data also confirm previous results and support hypotheses in current network models for the generation of the eupnoeic pattern.

Action Potentials↗
PubMed2000

Respiratory neural activity during long-term facilitation.

Intermittent hypoxia results in a long-term facilitation (LTF) of respiratory efferent activity. The studies reviewed here presented data from both anesthetized and decerebrate, paralyzed, vagotomized, artificially ventilated adult cats. Multiple arrays of tungsten microelectrodes were used to record the concurrent responses of brain stem neurons that contribute to respiratory motor pattern generation. Spike trains were analyzed with firing rate histograms, peristimulus time histograms, cycle triggered histograms, spike triggered averages with multiunit phrenic efferent activity, cross correlation histograms, joint peristimulus time histograms and the gravity method. These studies addressed several hypotheses. (1) There is parallel processing of input from carotid chemoreceptors to the brain stem. (2) Respiratory related midline neurons are involved in the induction and maintenance of LTF. (3) There is a change in effective connectivity of brain stem neurons with LTF. (4) Neural networks involved in the induction and maintenance of LTF have patterns of synchrony that recur with a frequency greater than expected by chance.

Animals↗
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.

Animals↗
PubMed2000

Repeated sequences of interspike intervals in baroresponsive respiratory related neuronal assemblies of the cat brain stem.

Many neurons exhibit spontaneous activity in the absence of any specific experimental perturbation. Patterns of distributed synchrony embedded in such activity have been detected in the brain stem, suggesting that it represents more than "baseline" firing rates subject only to being regulated up or down. This work tested the hypothesis that nonrandom sequences of impulses recur in baroresponsive respiratory-related brain stem neurons that are elements of correlational neuronal assemblies. In 15 Dial-urethan anesthetized vagotomized adult cats, neuronal impulses were monitored with microelectrode arrays in the ventral respiratory group, nucleus tractus solitarius, and medullary raphe nuclei. Efferent phrenic nerve activity was recorded. Spike trains were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Baroreceptors were stimulated by unilateral pressure changes in the carotid sinus or occlusion of the descending aorta; changes in firing rates were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Favored patterns of interspike interval sequences were detected in 31 of 58 single spike trains; 18 of the neurons with significant sequences also had short-time scale correlations with other simultaneously recorded cells. The number of distributed patterns exceeded that expected under the null hypothesis in 12 of 14 data sets composed of 4-11 simultaneously recorded spike trains. The data support the hypothesis that baroresponsive brain stem neurons operate in transiently configured coordinated assemblies and suggest that single neuron patterns may be fragments of distributed impulse sequences. The results further encourage the search for coding functions of spike patterns in the respiratory network.

Action Potentials↗
PubMed1999

Responses of simultaneously recorded respiratory-related medullary neurons to stimulation of multiple sensory modalities.

This study addresses the hypothesis that multiple afferent systems share elements of a distributed brain stem network that modulates the respiratory motor pattern. Data were collected from 18 decerebrate, bilaterally vagotomized, paralyzed, artificially ventilated cats. Up to 28 neurons distributed in the rostral and caudal ventral respiratory group, nucleus tractus solitarius, and raphe obscurus were recorded simultaneously with microelectrode arrays. Phases of the respiratory cycle and inspiratory drive were assessed from integrated efferent phrenic nerve activity. Carotid chemoreceptors were stimulated by injection of CO2-saturated saline solution via the external carotid artery. Baroreceptors were stimulated by increased blood pressure secondary to inflation of an embolectomy catheter in the descending aorta. Cutaneous nociceptors were stimulated by pinching a footpad. Four hundred seventy-four neurons were tested for respiratory modulated firing rates and responses; 403 neurons were tested with stimulation of all 3 modalities. Chemoreceptor stimulation and pinch, perturbations that tend to increase respiratory drive, caused similar responses in 52 neurons; 28 responded oppositely. Chemoreceptor and baroreceptor stimulation resulted in similar primary responses in 45 neurons; 48 responded oppositely. Similar responses to baroreceptor stimulation and pinch were recorded for 38 neurons; opposite effects were measured in 26 neurons. Among simultaneously recorded neurons, distinct combinations of firing rate changes were evoked in response to stimulation of the different modalities. The results show a functional convergence of information from carotid chemoreceptors, baroreceptors, and cutaneous nociceptors on respiratory-modulated neurons distributed in the medulla. The data are consistent with the hypothesis that brain stem neurons have overlapping memberships in multifunctional groups that influence the respiratory motor pattern.

Animals↗
PubMed1999

Multimodal medullary neurons and correlational linkages of the respiratory network.

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan-anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and "limit" changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.

Animals↗
PubMed1998

Medullary raphe neurones and baroreceptor modulation of the respiratory motor pattern in the cat.

1. Perturbations of arterial blood pressure change medullary raphe neurone activity and the respiratory motor pattern. This study sought evidence for actions of baroresponsive raphe neurones on the medullary respiratory network. 2. Blood pressure was perturbed by intravenous injection of an alpha1-adrenergic receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion of the descending aorta in thirty-six Dial-urethane-anaesthetized, vagotomized, paralysed, artificially ventilated cats. Neurones were monitored with microelectrode arrays in two or three of the following domains: nucleus raphe obscurus-nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal ventrolateral medulla. Data were analysed with cycle-triggered histograms, peristimulus time and cumulative sum histograms, cross-correlograms and spike-triggered averages of efferent phrenic nerve activity. 3. Prolongation of the expiratory phase and decreased peak integrated phrenic amplitude were most frequently observed. Of 707 neurones studied, 310 had altered firing rates during stimulation; changes in opposite directions were monitored simultaneously in fifty-six of eighty-seven data sets with at least two baroresponsive neurones. 4. Short time scale correlations were detected between neurones in 347 of 3388 pairs. Seventeen pairs of baroresponsive raphe neurones exhibited significant offset correlogram features indicative of paucisynaptic interactions. In correlated raphe-ventrolateral medullary neurone pairs with at least one baroresponsive neurone, six of seven ventrolateral medullary decrementing expiratory (E-Decr) neurones increased their firing rate during baroreceptor stimulation. Thirteen of fifteen ventrolateral medullary inspiratory neurones correlated with raphe cells decreased their firing rate during baroreceptor stimulation. 5. The results support the hypothesis that raphe neuronal assemblies transform and transmit information from baroreceptors to neurones in the ventral respiratory group. The inferred actions both limit and promote responses to sensory perturbations and match predictions from simulations of the respiratory network.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1998

Ventrolateral medullary respiratory network and a model of cough motor pattern generation.

The primary hypothesis of this study was that the cough motor pattern is produced, at least in part, by the medullary respiratory neuronal network in response to inputs from "cough" and pulmonary stretch receptor relay neurons in the nucleus tractus solitarii. Computer simulations of a distributed network model with proposed connections from the nucleus tractus solitarii to ventrolateral medullary respiratory neurons produced coughlike inspiratory and expiratory motor patterns. Predicted responses of various "types" of neurons (I-DRIVER, I-AUG, I-DEC, E-AUG, and E-DEC) derived from the simulations were tested in vivo. Parallel and sequential responses of functionally characterized respiratory-modulated neurons were monitored during fictive cough in decerebrate, paralyzed, ventilated cats. Coughlike patterns in phrenic and lumbar nerves were elicited by mechanical stimulation of the intrathoracic trachea. Altered discharge patterns were measured in most types of respiratory neurons during fictive cough. The results supported many of the specific predictions of our cough generation model and suggested several revisions. The two main conclusions were as follows: 1) The Bötzinger/rostral ventral respiratory group neurons implicated in the generation of the eupneic pattern of breathing also participate in the configuration of the cough motor pattern. 2) This altered activity of Bötzinger/rostral ventral respiratory group neurons is transmitted to phrenic, intercostal, and abdominal motoneurons via the same bulbospinal neurons that provide descending drive during eupnea.

Animals↗
PubMed1997

Repeated patterns of distributed synchrony in neuronal assemblies.

Models of brain function predict that the recurrence of a process or state will be reflected in repeated patterns of correlated activity. Previous work on medullary raphe assembly dynamics revealed transient changes in impulse synchrony. This study tested the hypothesis that these variations in synchrony include distributed nonrandom patterns of association. Spike trains were recorded simultaneously in the ventrolateral medulla, n. raphe obscurus, and n. raphe magnus of four anesthetized (Dial), vagotomized, paralyzed, and artificially ventilated adult cats. The "gravitational" representation of spike trains was used to detect moments of impulse synchrony in neuronal assemblies visualized as variations in the aggregation velocities of particles corresponding to each neuron. Template matching algorithms were developed to identify excessively repeating patterns of particle condensation rates. Repeating patterns were detected in each animal. The reiterated patterns represented an emergent property not apparent in either corresponding firing rate histograms or conventional gravity representations. Overlapping subsets of neurons represented in different patterns were unmasked when the template resolution was changed. The results demonstrate repeated transient network configurations defined by the tightness and duration of synchrony in different combinations of neurons and suggest that multiple information streams are conveyed concurrently by fluctuations in the synchrony of on-going activity.

Algorithms↗
PubMed1996

Inspiratory drive and phase duration during carotid chemoreceptor stimulation in the cat: medullary neurone correlations.

1. This study addressed the hypothesis that there is a parallel processing of input from carotid chemoreceptors to brainstem neurones involved in inspiratory phase timing and control of inspiratory motor output amplitude. Data were from fifteen anaesthetized, bilaterally vagotomized, paralysed, artificially ventilated cats. Carotid chemoreceptors were stimulated by close arterial injection of 200 microliters of CO2-saturated saline solution. 2. Planar arrays of tungsten microelectrodes were used to monitor simultaneously up to twenty-two neurones in the nucleus tractus solitarii (NTS) and ventral respiratory group (VRG). Spike trains were analysed with two statistical tests of respiratory modulation, cycle-triggered histograms, peristimulus-time histograms, cumulative sum histograms and cross-correlograms. 3. In NTS, 16 of 26 neurones with respiratory and 12 of 27 without respiratory modulation changed firing rate during carotid chemoreceptor stimulation. In the VRG 72 of 112 respiratory and 14 of 48 non-respiratory neurones changed firing rate during stimulation. 4. The spike trains of 85 of 1276 pairs (6.7%) of cells exhibited short time scale correlations indicative of paucisynaptic interactions. Ten pairs of neurones were each composed of a rostral VRG phasic inspiratory neurone that responded to carotid chemoreceptor stimulation with a decline in firing rate and a caudal VRG phasic inspiratory neurone that increased its firing rate. Cross-correlograms from two of the pairs had features consistent with excitation of the caudal neurones by the rostral cells. A decrease in the duration of activity of the rostral VRG neurones was paralleled by the decrease in inspiratory time of phrenic nerve activity. Caudal VRG inspiratory neurones increased their activity as phrenic amplitude increased. Spike-triggered averages of all four neurones indicated post-spike facilitation of phrenic motoneurones. 5. The results support the hypothesis that unilateral stimulation of carotid chemoreceptors results in parallel actions. (a) Inhibition of rostral VRG I-Driver neurones decreases inspiratory duration. (b) Concurrent excitation of premotor VRG and dorsal respiratory group inspiratory neurones increases inspiratory drive to phrenic motoneurones. Other data suggest that responsive ipsilateral neurones act to regulate contralateral neurones.

Animals↗
PubMed1996

Long-term facilitation of phrenic nerve activity in cats: responses and short time scale correlations of medullary neurones.

1. Stimulation of either peripheral chemoreceptors or nucleus raphe obscurus results in long-term facilitation of phrenic motoneurone activity. The first objective of this work was to measure the concurrent responses of neurones in the nucleus raphe obscurus, the nucleus tractus solitarii, and the regions of the retrofacial nucleus, nucleus ambiguus and nucleus retroambigualis during induction of long-term facilitation. A second goal was to assess functional relationships of the chemoresponsive raphe neurones with neurones in the other monitored locations and with phrenic motoneurones. 2. Up to thirty single medullary neurones and phrenic nerve efferent activity were recorded simultaneously in fifteen anaesthetized, paralysed, vagotomized, artificially ventilated adult cats. Carotid chemoreceptors were stimulated by close arterial injection of 200 microliters of CO2-saturated saline solution. Spike trains were analysed with cycle-triggered histograms and two statistical tests for respiratory modulation. Peristimulus-time histograms and cumulative sum histograms were used to assess responses to stimulation. Cross-correlation was used to test for non-random temporal relationships between spike trains. Spike-triggered average histograms provided evidence for functional associations with phrenic motoneurones. 3. One hundred and thirteen of 348 neurones were monitored in the nucleus raphe obscurus. The firing rates of twenty-nine raphe neurones increased during stimulation; eighteen decreased. In twenty-one pairs of concurrently monitored raphe neurones, the firing rate of one increased its activity during stimulation then decreased, while the other showed an increase that began as the rate of the former declined. Eighteen chemoresponsive raphe neurones had short time scale features in their phrenic spike-triggered averages. Short time scale features were found in cross-correlograms from 184 of 1407 neurone pairs. 4. The data suggest parallel routes by which carotid chemoreceptors influence medullary raphe neurones and support the hypotheses that mid-line respiratory-related neuronal assemblies transform information from those receptors and regulate the gain of respiratory motor output.

Animals↗
PubMed1994

Simulations of a ventrolateral medullary neural network for respiratory rhythmogenesis inferred from spike train cross-correlation.

Connections among ventrolateral medullary respiratory neurons inferred from spike train analysis were incorporated into a model and simulated with the program SYSTM11 (MacGregor 1987). Inspiratory (I) and expiratory (E) neurons with augmenting (AUG) and decrementing (DEC) discharge patterns and rostral I-E/I neurons exhibited varying degrees of adaptation, but no endogenous bursting properties. Simulation parameters were adjusted so that respiratory phase durations, neuronal discharge patterns, and short-time scale correlations were similar to corresponding measurements from anesthetized, vagotomized, adult cats. Rhythmogenesis persisted when the strength of each set of connections was increased 100% over a smaller effective value. Changes in phase durations and discharge patterns caused by manipulation of connection strengths or population activity led to several predictions. (a) Excitation of the I-E/I population prolongs the inspiratory phase. (b) Rhythmic activity can be reestablished in the absence of I-E/I activity by unpatterned excitation of I-DEC and I-AUG neurons. (c) An increase in I-DEC neuron activity can cause an apneustic respiratory pattern. (d) A decrease in I-DEC neuron activity increases the slope of the inspiratory ramp and shortens inspiration. (e) Excitation of the E-DEC population prolongs the expiratory phase or produces apnea; inhibition of E-DEC neurons reduces expiratory time. (f) Excitation of E-AUG cells causes I-AUG neurons to exhibit a step rather than a ramp increase in firing rate at the onset of their active phase. The results suggest mechanisms by which the duration of each phase of breathing and neuronal discharge patterns may be regulated.

Animals↗
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)

Animals↗