Search PubMed⌕ Search

Biomedical subjects

K F Morris

Publications and source records attributed to K F Morris.

24 records · Page 2Linked to original sources

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↗

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↗

Functional connectivity between brain stem midline neurons with respiratory-modulated firing rates.

1. Recent evidence supports the idea that neurons distributed along the midline of the brain stem contribute to the regulation of breathing. This study sought evidence for functional connections between midline neurons with respiratory-modulated firing rates. 2. Experiments were conducted on 38 anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Planar arrays of tungsten microelectrodes were used to monitor spike trains of two or more midline neurons simultaneously in the regions of n. raphe obscurus, n. raphe pallidus, and n. raphe magnus. Efferent phrenic nerve activity was recorded. Data were analyzed with auto- and cross-correlograms and cycle-triggered histograms. Spike trains of neurons were also tested for respiratory modulation by an analysis of variance with the use of a subjects-by-treatments experimental design. 3. Of 584 neurons studied, 99.1% were tonic, i.e., they had firing probabilities greater than zero in all phases of the respiratory cycle. Fifty-three percent of the neurons had respiratory-modulated firing rates; 223 cells were more active during the expiratory (E) interval; 88 neurons were inspiratory (I)-related. The remaining cells were classified as having no respiratory-related modulation of firing rate (NRR). 4. The spike trains of 210 of 1,078 pairs (19.5%) of brain stem midline neurons exhibited short-time scale correlations indicative of paucisynaptic interactions. Primary cross-correlogram features included 129 central peaks, 45 offset peaks, two central troughs, and 57 offset troughs. Twenty-two of the neuronal pairs analyzed had both offset peaks and troughs. Correlograms from an additional 35 pairs of neurons had multiple peaks and troughs without a significant primary feature. 5. The frequency of correlations for neuron pairs composed of cells with respiratory-modulated firing rates was as follows: E-E, 40/185 (22%); E-I, 23/111 (21%); E-NRR, 45/297 (15%); I-I, 11/25 (44%); and I-NRR, 13/104 (13%). Twenty-two percent of the NRR pairs (79/357) exhibited short-time scale correlations. 6. Thirty pairs of neurons included a cell with an antidromically identified axonal projection extending to at least the third cervical segment. The mean estimated conduction velocity based on the single-site stimulation method was 26.5 +/- 9.9 (SD) m/s. 7. The results provide evidence for inhibitory and excitatory functional connections between midline brain stem neurons. Data support the hypothesis that the respiratory-modulated discharge patterns of midline neurons are, at least in part, a consequence of the synaptic actions of other midline cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

Respiratory-related neural assemblies in the brain stem midline.

1. The initial objective of this study was to determine whether respiratory-related neural assemblies exist in the brain stem midline. A second goal was to seek evidence for concurrent relationships among the neurons that could generate the detected synchrony. 2. Experiments were conducted on anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Spike trains of four to nine simultaneously monitored neurons were recorded in the regions of n. raphe obscurus-n. raphe pallidus and n. raphe magnus. 3. Data were analyzed with cycle-triggered histograms, cross-correlograms, snowflakes, and the gravitational representation. A significance test for the gravity method was developed and tested with spike trains generated by simulated networks with defined connections. 4. Ninety-three groups of neurons from 24 cats were studied. Thirty-nine groups from 19 cats included neurons that discharged synchronously on a millisecond time scale; less than or equal to 19 pairs of synchronously discharging neurons were found in one group. Twenty-seven of these 39 groups included neurons that had respiratory-modulated firing rates and discharged synchronously with other group members. Synchronous assemblies included cells monitored at rostral or caudal locations, or both. 5. Six classes of relationships were inferred from groups of neurons with multiple correlations: divergence (n = 11); convergence (n = 7); connections with opposite actions between neurons (n = 5); projections of synchronous neurons to separate targets (n = 5); projections to one neuron in a synchronous group (n = 4); and projections between two synchronous groups with common elements (n = 6). 6. The results document the existence of assemblies of synchronously discharging respiratory-related neurons in midline regions of the brain stem and suggest that divergent excitatory and inhibitory connections within the midline participate in the generation of that synchrony. Links between assemblies may operate to stabilize their collective activity in a particular state.

Afferent Pathways↗

Dynamic reconfiguration of brain stem neural assemblies: respiratory phase-dependent synchrony versus modulation of firing rates.

1. The objective of this work was to determine whether configurations of midline brain stem neural assemblies change during the respiratory cycle. 2. Spike trains of several single neurons were recorded simultaneously in anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Data were analyzed with cross-correlational and gravity methods. 3. Sequential samples from each of eight groups of neurons known to contain synchronously discharging neurons exhibited temporal variations in that synchrony. 4. Gravity analysis of short (less than 200-s) samples of spike train data revealed 20 pairs of clustered particles that were not predicted from cross-correlation analysis of the parent data sets (greater than 20 min). 5. Twenty-nine groups of three to eight simultaneously monitored neurons, each with at least two synchronously discharging neurons, were analyzed for evidence of respiratory phase-dependent modulation of that coordinated activity. Spikes from successive interleaved inspiratory and expiratory intervals were analyzed separately. 6. Neurons pairs in 11 groups were more synchronous during the inspiratory interval; six groups had pairs that were more synchronous during the expiratory period. In two groups, different pairs were synchronous in different respiratory phases. In 11 of the 26 pairs that exhibited phase-dependent differences in synchrony, neither neuron had a respiratory-modulated firing rate as judged by either the cycle-triggered histogram or an analysis of variance of their firing rates. 7. Configurations of respiratory-related brain stem neural networks changed with time and the phases of breathing. Neurons with no apparent respiratory modulation of their individual firing rates collectively exhibited respiratory phase-dependent modulation of their impulse synchrony.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Brainstem respiratory networks and cough.

The focus of this review is work that supports a model of the medullary neuronal network that is involved in producing the cough motor pattern of inspiratory and expiratory pump muscles. Evidence is presented that supports the following hypotheses: (1) Bulbospinal drive to respiratory motoneurons during cough arises, at least in part, from the same medullary neurons involved in providing drive during eupnoea. (2) Medullary Bötzinger/ rostral ventral respiratory group neurons implicated in generating and shaping the eupnoeic pattern of breathing are also involved in producing the central cough motor pattern. The results were not consistent with a "cough centre" separate from the BOT/VRG. Observed neurons (in cats) included most of all previously identified respiratory modulated "types". The results showed that there were alterations in discharge patterns of all respiratory neurons during fictive cough. Many "types" responded as predicted by cough model network simulations. Based on neuron behaviours in our studies and inferred synaptic actions among BOT/VRG neurons, we propose a preliminary model for cough generation by the BOT/rVRG network.

Animals↗