B G Lindsey

University of Florida, Gainesville, FL, United States

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Publications (64)175.79 Total impact

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    ABSTRACT: Models of brainstem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" peri-columnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multi-electrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pair-wise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In 5 animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons.
    Journal of neurophysiology. 10/2014;
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    ABSTRACT: Airway protection is the prevention and/or removal of material by behaviors, such as cough and swallow. We tested the hypothesis that cough and swallow, in response to aspiration, are a "meta-behavior" and thus are coordinated and have alterations in excitability to respond to aspiration risk and maintain homeostasis. Anesthetized animals were challenged with a protocol that simulated ongoing aspiration and induced both coughing and swallowing. Electromyograms of the mylohyoid, geniohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus, parasternal, rectus abdominis muscles together with esophageal pressure were recorded to identify and evaluate cough and swallow. During simulated aspiration, both cough and swallow intensity increased and swallow duration decreased consistent with a more rapid pharyngeal clearance. A phase restriction between cough and swallow was also observed; swallow was restricted to the E2 phase of cough during chest wall and abdominal motor quiescence. These results support the conclusion that the cough and swallow pattern generators are an airway protective meta-behavior. The resulting alterations in swallow drive during the simulated aspiration protocol also supports the conclusion that the trachea provides feedback on swallow quality, informing the brainstem about aspiration incidences. The overall coordination of cough and swallow led to the additional conclusion that mechanically the larynx and upper esophageal sphincter act as two separate valves controlling the direction of positive and negative pressures from the upper airway into the thorax.
    Respiratory Physiology & Neurobiology 08/2013; · 2.05 Impact Factor
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    Bruce G Lindsey, Ilya A Rybak, Jeffrey C Smith
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    ABSTRACT: Computational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data-driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre-Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state-dependent expression of different neural pattern-generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered.
    Comprehensive Physiology. 07/2012; 2(3):1619-1670.
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    ABSTRACT: Ventrolateral respiratory column (VRC) circuits that modulate breathing in response to changes in central chemoreceptor drive are incompletely understood. We employed multielectrode arrays and spike train correlation methods to test predictions of the hypothesis that pre-Bötzinger complex (pre-BötC) and retrotrapezoid nucleus/parafacial (RTN-pF) circuits cooperate in chemoreceptor-evoked tuning of ventral respiratory group (VRG) inspiratory neurons. Central chemoreceptors were selectively stimulated by injections of CO(2)-saturated saline into the vertebral artery in seven decerebrate, vagotomized, neuromuscularly blocked, and artificially ventilated cats. Among sampled neurons in the Bötzinger complex (BötC)-to-VRG region, 70% (161 of 231) had a significant change in firing rate after chemoreceptor stimulation, as did 70% (101 of 144) of the RTN-pF neurons. Other responsive neurons (24 BötC-VRG; 11 RTN-pF) had a change in the depth of respiratory modulation without a significant change in average firing rate. Seventy BötC-VRG chemoresponsive neurons triggered 189 offset-feature correlograms (96 peaks; 93 troughs) with at least one responsive BötC-VRG cell. Functional input from at least one RTN-pF cell could be inferred for 45 BötC-VRG neurons (19%). Eleven RTN-pF cells were correlated with more than one BötC-VRG target neuron, providing evidence for divergent connectivity. Thirty-seven RTN-pF neurons, 24 of which were chemoresponsive, were correlated with at least one chemoresponsive BötC-VRG neuron. Correlation linkage maps and spike-triggered averages of phrenic nerve signals suggest transmission of chemoreceptor drive via a multipath network architecture: RTN-pF modulation of pre-BötC-VRG rostral-to-caudal excitatory inspiratory neuron chains is tuned by feedforward and recurrent inhibition from other inspiratory neurons and from "tonic" expiratory neurons.
    Journal of Neurophysiology 01/2012; 107(2):603-17. · 3.30 Impact Factor
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    ABSTRACT: Data-driven computational neural network models have been used to study mechanisms for generating the motor patterns for breathing and breathing related behaviors such as coughing. These models have commonly been evaluated in open loop conditions or with feedback of lung volume simply represented as a filtered version of phrenic motor output. Limitations of these approaches preclude assessment of the influence of mechanical properties of the musculoskeletal system and motivated development of a biomechanical model of the respiratory muscles, airway, and lungs using published measures from human subjects. Here we describe the model and some aspects of its behavior when linked to a computational brainstem respiratory network model for breathing and airway defensive behavior composed of discrete "integrate and fire" populations. The network incorporated multiple circuit paths and operations for tuning inspiratory drive suggested by prior work. Results from neuromechanical system simulations included generation of a eupneic-like breathing pattern and the observation that increased respiratory drive and operating volume result in higher peak flow rates during cough, even when the expiratory drive is unchanged, or when the expiratory abdominal pressure is unchanged. Sequential elimination of the model's sources of inspiratory drive during cough also suggested a role for disinhibitory regulation via tonic expiratory neurons, a result that was subsequently supported by an analysis of in vivo data. Comparisons with antecedent models, discrepancies with experimental results, and some model limitations are noted.
    Frontiers in Physiology 01/2012; 3:264.
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    ABSTRACT: This study investigated the stability of the discharge identity of inspiratory decrementing (I-Dec) and augmenting (I-Aug) neurons in the caudal (cVRC) and rostral (rVRC) ventral respiratory column during repetitive fictive cough in the cat. Inspiratory neurons in the cVRC (n = 23) and rVRC (n = 17) were recorded with microelectrodes. Fictive cough was elicited by mechanical stimulation of the intrathoracic trachea. Approximately 43% (10 of 23) of I-Dec neurons shifted to an augmenting discharge pattern during the first cough cycle (C1). By the second cough cycle (C2), half of these returned to a decrementing pattern. Approximately 94% (16 of 17) of I-Aug neurons retained an augmenting pattern during C1 of a multi-cough response episode. Phrenic burst amplitude and inspiratory duration increased during C1, but decreased with each subsequent cough in a series of repetitive coughs. As a step in evaluating the model-driven hypothesis that VRC I-Dec neurons contribute to the augmentation of inspiratory drive during cough via inhibition of VRC tonic expiratory neurons that inhibit premotor inspiratory neurons, cross-correlation analysis was used to assess relationships of tonic expiratory cells with simultaneously recorded inspiratory neurons. Our results suggest that reconfiguration of inspiratory-related sub-networks of the respiratory pattern generator occurs on a cycle-by-cycle basis during repetitive coughing.
    Frontiers in Physiology 01/2012; 3:223.
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    ABSTRACT: Coughing and swallowing are airway-protective behaviours. The pharyngeal phase of swallowing prevents aspiration of oral material (saliva, food and liquid) by epiglottal movement, laryngeal adduction and clearing of the mouth and pharynx. Coughing is an aspiration-response behaviour that removes material from the airway. Co-ordination of these behaviours is vital to protect the airway from further aspiration-promoting events, such as a swallowing during the inspiratory phase of coughing. The operational characteristics, primary strategies and peripheral inputs that co-ordinate coughing and swallowing are unknown. This lack of knowledge impedes understanding and treatment of deficits in airway protection, such as the co-occurrence of dystussia and dysphagia common in Parkinson's and Alzheimer's diseases, as well as stroke.
    Experimental physiology 12/2011; 97(4):469-73. · 3.17 Impact Factor
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    ABSTRACT: We tested the hypothesis, motivated in part by a coordinated computational cough network model, that alterations of mean systemic arterial blood pressure (BP) influence the excitability and motor pattern of cough. Model simulations predicted suppression of coughing by stimulation of arterial baroreceptors. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase of cough, and prolonged the cough inspiratory and expiratory phases as well as cough cycle duration compared with control coughs. Latencies from the beginning of stimulation to the onset of cough-related diaphragm and abdominal activities were increased. Increases in BP also elicited bradycardia and isocapnic bradypnea. Reductions in BP increased cough number; elevated inspiratory EP amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes; decreased total cough cycle duration; shortened the durations of the cough expiratory phase and cough-related abdominal discharge; and shortened cough latency compared with control coughs. Reduced BP also produced tachycardia, tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing likely originate from interactions between barosensitive and respiratory brainstem neuronal networks, particularly by modulation of respiratory neurons within multiple respiration/cough-related brainstem areas by baroreceptor input.
    Journal of Applied Physiology 06/2011; 111(3):861-73. · 3.48 Impact Factor
  • Pulmonary Pharmacology &amp Therapeutics 06/2011; 24(3):e5–e6. · 2.54 Impact Factor
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    ABSTRACT: The medullary ventral respiratory column (VRC) of neurons is essential for respiratory motor pattern generation; however, the functional connections among these cells are not well understood. A rostral extension of the VRC, including the retrotrapezoid nucleus/parafacial region (RTN-pF), contains neurons responsive to local perturbations of CO(2)/pH. We addressed the hypothesis that both local RTN-pF interactions and functional connections from more caudal VRC compartments--extending from the Bötzinger and pre-Bötzinger complexes to the ventral respiratory group (Böt-VRG)--influence the respiratory modulation of RTN-pF neurons and their responses to central chemoreceptor and baroreflex activation. Spike trains from 294 RTN-pF and 490 Böt-VRG neurons were monitored with multielectrode arrays along with phrenic nerve activity in 14 decerebrate, vagotomized cats. Overall, 214 RTN-pF and 398 Böt-VRG neurons were respiratory modulated; 124 and 95, respectively, were cardiac modulated. Subsets of these neurons were tested with sequential, selective, transient stimulation of central chemoreceptors and arterial baroreceptors; each cell's response was evaluated and categorized according to the change in firing rate (if any) following the stimulus. Cross-correlation analysis was applied to 2,884 RTN-pF↔RTN-pF and 8,490 Böt-VRG↔RTN-pF neuron pairs. In total, 174 RTN-pF neurons (59.5%) had significant features in short-time scale correlations with other RTN-pF neurons. Of these, 49 neurons triggered cross-correlograms with offset peaks or troughs (n = 99) indicative of paucisynaptic excitation or inhibition of the target. Forty-nine Böt-VRG neurons (10.0%) were triggers in 74 Böt-VRG→RTN-pF correlograms with offset features, suggesting that Böt-VRG trigger neurons influence RTN-pF target neurons. The results support the hypothesis that local RTN-pF neuron interactions and inputs from Böt-VRG neurons jointly contribute to respiratory modulation of RTN-pF neuronal discharge patterns and promotion or limitation of their responses to central chemoreceptor and baroreceptor stimulation.
    Journal of Neurophysiology 03/2011; 105(6):2960-75. · 3.30 Impact Factor
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    ABSTRACT: A method for visualization of dynamic multidimensional data—L-plotting, similar to recurrence plotting, is described. For multi-neuronal brainstem recordings the method demonstrates that the neural respiratory pattern generator (RPG) switches between the two phases: inspiratory and expiratory. The method helps to mark phase switching moments and to characterize the pattern of the RPG restart after temporary cessation of rhythmicity. Comparison of L-plots for experimental data and network simulations helps verification of computational models.
    Neurocomputing 12/2010; · 2.01 Impact Factor
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    ABSTRACT: Previous models have attributed changes in respiratory modulation of pontine neurons after vagotomy to a loss of pulmonary stretch receptor "gating" of an efference copy of inspiratory drive. Recently, our group confirmed that pontine neurons change firing patterns and become more respiratory modulated after vagotomy, although average peak and mean firing rates of the sample did not increase (Dick et al., J Physiol 586: 4265-4282, 2008). Because raphé neurons are also elements of the brain stem respiratory network, we tested the hypotheses that after vagotomy raphé neurons have increased respiratory modulation and that alterations in their firing patterns are similar to those seen for pontine neurons during withheld lung inflation. Raphé and pontine neurons were recorded simultaneously before and after vagotomy in decerebrated cats. Before vagotomy, 14% of 95 raphé neurons had increased activity during single respiratory cycles prolonged by withholding lung inflation; 13% exhibited decreased activity. After vagotomy, the average index of respiratory modulation (eta(2)) increased (0.05 +/- 0.10 to 0.12 +/- 0.18 SD; Student's paired t-test, P < 0.01). Time series and frequency domain analyses identified pontine and raphé neuron firing rate modulations with a 0.1-Hz rhythm coherent with blood pressure Mayer waves. These "Mayer wave-related oscillations" (MWROs) were coupled with central respiratory drive and became synchronized with the central respiratory rhythm after vagotomy (7 of 10 animals). Cross-correlation analysis identified functional connectivity in 52 of 360 pairs of neurons with MWROs. Collectively, the results suggest that a distributed network participates in the generation of MWROs and in the coordination of respiratory and vasomotor rhythms.
    Journal of Applied Physiology 04/2010; 109(1):189-202. · 3.48 Impact Factor
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    ABSTRACT: The brainstem network for generating and modulating the respiratory motor pattern includes neurons of the medullary ventrolateral respiratory column (VRC), dorsolateral pons (PRG) and raphé nuclei. Midline raphé neurons are proposed to be elements of a distributed brainstem system of central chemoreceptors, as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus. Stimulation of the raphé system or peripheral chemoreceptors can induce a long-term facilitation of phrenic nerve activity; central chemoreceptor stimulation does not. The network mechanisms through which each class of chemoreceptor differentially influences breathing are poorly understood. Microelectrode arrays were used to monitor sets of spike trains from 114 PRG, 198 VRC and 166 midline neurons in six decerebrate vagotomized cats; 356 were recorded during sequential stimulation of both receptor classes via brief CO(2)-saturated saline injections in vertebral (central) and carotid arteries (peripheral). Seventy neurons responded to both stimuli. More neurons were responsive only to peripheral challenges than those responsive only to central chemoreceptor stimulation (PRG, 20 : 4; VRC, 41 : 10; midline, 25 : 13). Of 16 474 pairs of neurons evaluated for short-time scale correlations, similar percentages of reference neurons in each brain region had correlation features indicative of a specific interaction with at least one target neuron: PRG (59.6%), VRC (51.0%) and raphé nuclei (45.8%). The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor-mediated influences on breathing.
    Philosophical Transactions of The Royal Society B Biological Sciences 10/2009; 364(1529):2501-16. · 6.23 Impact Factor
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    ABSTRACT: Cardio-respiratory coupling is reciprocal; it is expressed as respiratory-modulated sympathetic nerve activity and pulse-modulated respiratory motor activity. In the brainstem, the neuraxis controlling cardio-respiratory functions forms a ventrolateral cell column which extends to the dorsolateral (dl) pons. Our general working hypothesis is that these control systems converge at points with the common purpose of gas exchange and that neural activity along this axis coordinates both arterial pulse pressure and breathing. Here, we review the data showing that pontine nuclei modulate heart rate, blood pressure and breathing, and present new results demonstrating a vagal influence on pontine activity modulated with both arterial pulse pressure and phrenic nerve activity in the decerebrate cat. Generally with the vagi intact, dl pontine activity was weakly modulated by both arterial pulse pressure and respiratory pattern. After bilateral vagotomy, the strength and consistency of respiratory modulation increased significantly, although the strength and consistency of arterial pulse pressure modulation did not change significantly for the group; a decrease in some (62%) was offset by an increase in others (36%) neurons. Thus, the vagus shapes the envelope of the cycle-triggered averages of neural activity for both the respiratory and cardiac cycles. These data provide insight into the neural substrate for the prominent vagal effect on the cardio-respiratory coupling pattern, in particular respiratory sinus arrhythmia. While these results support convergence of inputs to neural populations controlling breathing and cardiovascular functions, the physiologic role of balancing ventilation, vascular resistance, heart rate and blood flow for the benefit of tissue oxygenation, remains hypothetical.
    Respiratory Physiology & Neurobiology 08/2009; 168(1-2):76-85. · 2.05 Impact Factor
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    ABSTRACT: Recently, Segers et al. identified functional connectivity between the ventrolateral respiratory column (VRC) and the pontine respiratory group (PRG). The apparent sparseness of detected paucisynaptic interactions motivated consideration of other potential functional pathways between these two regions. We report here evidence for "indirect" serial functional linkages between the PRG and VRC via intermediary brain stem midline raphé neurons. Arrays of microelectrodes were used to record sets of spike trains from a total of 145 PRG, 282 VRC, and 340 midline neurons in 11 decerebrate, vagotomized, neuromuscularly blocked, ventilated cats. Spike trains of 13,843 pairs of neurons that included at least one raphé cell were screened for respiratory modulation and short-time scale correlations. Significant correlogram features were detected in 7.2% of raphé-raphé (291/4,021), 4.3% of VRC-raphé (292/6,755), and 4.0% of the PRG-raphé (124/3,067) neuron pairs. Central peaks indicative of shared influences were the most common feature in correlations between pairs of raphé neurons, whereas correlated raphé-PRG and raphé-VRC neuron pairs displayed predominantly offset peaks and troughs, features suggesting a paucisynaptic influence of one neuron on the other. Overall, offset correlogram features provided evidence for 33 VRC-to-raphé-to-PRG and 45 PRG-to-raphé-to-VRC correlational linkage chains with one or two intermediate raphé neurons. The results support a respiratory network architecture with parallel VRC-to-PRG and PRG-to-VRC links operating through intervening midline circuits, and suggest that raphé neurons contribute to the respiratory modulation of PRG neurons and shape the respiratory motor pattern through coordinated divergent actions on both the PRG and VRC.
    Journal of Neurophysiology 04/2009; 101(6):2943-60. · 3.30 Impact Factor
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    ABSTRACT: A large body of data suggests that the pontine respiratory group (PRG) is involved in respiratory phase-switching and the reconfiguration of the brain stem respiratory network. However, connectivity between the PRG and ventral respiratory column (VRC) in computational models has been largely ad hoc. We developed a network model with PRG-VRC connectivity inferred from coordinated in vivo experiments. Neurons were modeled in the "integrate-and-fire" style; some neurons had pacemaker properties derived from the model of Breen et al. We recapitulated earlier modeling results, including reproduction of activity profiles of different respiratory neurons and motor outputs, and their changes under different conditions (vagotomy, pontine lesions, etc.). The model also reproduced characteristic changes in neuronal and motor patterns observed in vivo during fictive cough and during hypoxia in non-rapid eye movement sleep. Our simulations suggested possible mechanisms for respiratory pattern reorganization during these behaviors. The model predicted that network- and pacemaker-generated rhythms could be co-expressed during the transition from gasping to eupnea, producing a combined "burst-ramp" pattern of phrenic discharges. To test this prediction, phrenic activity and multiple single neuron spike trains were monitored in vagotomized, decerebrate, immobilized, thoracotomized, and artificially ventilated cats during hypoxia and recovery. In most experiments, phrenic discharge patterns during recovery from hypoxia were similar to those predicted by the model. We conclude that under certain conditions, e.g., during recovery from severe brain hypoxia, components of a distributed network activity present during eupnea can be co-expressed with gasp patterns generated by a distinct, functionally "simplified" mechanism.
    Journal of Neurophysiology 10/2008; 100(4):1770-99. · 3.30 Impact Factor
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    ABSTRACT: Current models propose that a neuronal network in the ventrolateral medulla generates the basic respiratory rhythm and that this ventrolateral respiratory column (VRC) is profoundly influenced by the neurons of the pontine respiratory group (PRG). However, functional connectivity among PRG and VRC neurons is poorly understood. This study addressed four model-based hypotheses: 1) the respiratory modulation of PRG neuron populations reflects paucisynaptic actions of multiple VRC populations; 2) functional connections among PRG neurons shape and coordinate their respiratory-modulated activities; 3) the PRG acts on multiple VRC populations, contributing to phase-switching; and 4) neurons with no respiratory modulation located in close proximity to the VRC and PRG have widely distributed actions on respiratory-modulated cells. Two arrays of microelectrodes with individual depth adjustment were used to record sets of spike trains from a total of 145 PRG and 282 VRC neurons in 10 decerebrate, vagotomized, neuromuscularly blocked, ventilated cats. Data were evaluated for respiratory modulation with respect to efferent phrenic motoneuron activity and short-timescale correlations indicative of paucisynaptic functional connectivity using cross-correlation analysis and the "gravity" method. Correlogram features were found for 109 (3%) of the 3,218 pairs composed of a PRG and a VRC neuron, 126 (12%) of the 1,043 PRG-PRG pairs, and 319 (7%) of the 4,340 VRC-VRC neuron pairs evaluated. Correlation linkage maps generated for the data support our four motivating hypotheses and suggest network mechanisms for proposed modulatory functions of the PRG.
    Journal of Neurophysiology 10/2008; 100(4):1749-69. · 3.30 Impact Factor
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    ABSTRACT: The dorsolateral (DL) pons modulates the respiratory pattern. With the prevention of lung inflation during central inspiratory phase (no-inflation (no-I or delayed-I) tests), DL pontine neuronal activity increased the strength and consistency of its respiratory modulation, properties measured statistically by the eta(2) value. This increase could result from enhanced respiratory-modulated drive arising from the medulla normally gated by vagal activity. We hypothesized that DL pontine activity during delayed-I tests would be comparable to that following vagotomy. Ensemble recordings of neuronal activity were obtained before and after vagotomy and during delayed-I tests in decerebrate, paralysed and ventilated cats. In general, changes in activity pattern during the delayed-I tests were similar to those after vagotomy, with the exception of firing-rate differences at the inspiratory-expiratory phase transition. Even activity that was respiratory-modulated with the vagi intact became more modulated while withholding lung inflation and following vagotomy. Furthermore, we recorded activity that was excited by lung inflation as well as changes that persisted past the stimulus cycle. Computer simulations of a recurrent inhibitory neural network model account not only for enhanced respiratory modulation with vagotomy but also the varied activities observed with the vagi intact. We conclude that (a) DL pontine neurones receive both vagal-dependent excitatory inputs and central respiratory drive; (b) even though changes in pontine activity are transient, they can persist after no-I tests whether or not changes in the respiratory pattern occur in the subsequent cycles; and (c) models of respiratory control should depict a recurrent inhibitory circuitry, which can act to maintain the stability and provide plasticity to the respiratory pattern.
    The Journal of Physiology 08/2008; 586(Pt 17):4265-82. · 4.38 Impact Factor
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    Cough: Causes, Mechanisms and Therapy, 01/2008: pages 173 - 180; , ISBN: 9780470755846
  • Bruce G Lindsey, George L Gerstein
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    ABSTRACT: The gravity method for neuronal assembly analysis represents each neuron as a particle in N-space with a time varying charge that is a filtered version of the corresponding spike train, with appropriate rules for forces between and movements of the charged particles. Resulting trajectories reflect neuronal timing relationships. The usual short time constants in the filter restrict aggregation to highly synchronized neurons and reduce the sensitivity for delayed correlations; long time constants in the filter reduce selectivity. Here we describe an enhancement that modifies rules for assigning charge increment times to allow mixtures of short and long lag correlations. Charge increments for each pair are offset from the actual spike times by time lags defined by features in corresponding cross-correlograms; no such charge offsets are invoked if the correlogram is flat. Tuning increases charge products and aggregation of long lag correlated pairs. A second enhancement uses a new three-dimensional display of particle pair trajectories to parse the type of neuronal relationship. For each pair, we record and display the inter-particle distance and the distance each particle moves from its original location in the N-space. The resulting trajectories cluster according to the type of interaction between the represented neurons. Results from simulated networks and in vivo multi-site recordings show that these modifications detect assembly properties not identified by the standard methods.
    Journal of Neuroscience Methods 02/2006; 150(1):116-27. · 2.11 Impact Factor

Publication Stats

1k Citations
175.79 Total Impact Points

Institutions

  • 1993–2013
    • University of Florida
      • Department of Physiological Sciences
      Gainesville, FL, United States
  • 1982–2013
    • University of South Florida
      • • Division of Molecular Pharmacology & Physiology
      • • Department of Molecular Pharmacology & Physiology
      • • Morsani College of Medicine
      Tampa, Florida, United States
  • 2005–2009
    • Case Western Reserve University
      • • Division of Pulmonary, Critical Care and Sleep Medicine
      • • Department of Medicine (University Hospitals Case Medical Center)
      Cleveland, OH, United States
  • 2008
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • Drexel University College of Medicine
      • Department of Neurobiology & Anatomy
      Philadelphia, PA, United States