Response of the Respiratory Network of Mice to Hyperthermia

2003 ◽  
Vol 89 (6) ◽  
pp. 2975-2983 ◽  
Author(s):  
Andrew K. Tryba ◽  
Jan-Marino Ramirez
Keyword(s):  
Neural Network ◽  
Heat Stroke ◽  
Brain Structures ◽  
Bath Temperature ◽  
Motor Nucleus ◽  
Temperature Modulation ◽  
Population Activity ◽  
Temperature Changes ◽  
Respiratory Network ◽  
Burst Amplitude

Most mammals modulate respiratory frequency (RF) to dissipate heat (i.e., panting) and avoid heat stroke during hyperthermic conditions. During hyperthermia, the RF of intact mammals increases and then declines or ceases (apnea). It has been proposed that this RF modulation depends on the presence of higher brain structures such as the hypothalamus. However, the direct effects of hyperthermia on the respiratory neural network have not been examined. To address this issue, the respiratory neural network [i.e., ventral respiratory group (VRG)] was isolated in a brain stem preparation taken from the medulla of mice (P0 –P6). Integrated population activity, predominated by inspiratory neurons, was recorded extracellularly from VRG neurons. The bath temperature was then heated from 30 to 40°C, resulting in a biphasic frequency response in VRG activity. Following an initial six- to sevenfold increase and subsequent decline, fictive RF was maintained at a frequency that was higher than baseline frequency; at 40°C, the RF was maintained at about two to four times that at 30°C. The inspiratory burst amplitude and duration were significantly reduced during hyperthermic conditions. An increase in RF and decrease in VRG burst amplitude and duration also occurred when heating from 37 to 40°C. Fictive apnea typically occurred during cooling to the control temperature. Furthermore, changes in hypoglossal motor nucleus activity paralleled those of the VRG, suggesting that temperature modulation of the VRG is likely to have a behaviorally relevant impact on respiration. We conclude that the VRG activity itself is modulated during hyperthermia and the respiratory network is particularly sensitive to temperature changes.

Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids

1993 ◽  
Vol 70 (4) ◽  
pp. 1497-1515 ◽  
Author(s):  
G. D. Funk ◽  
J. C. Smith ◽  
J. L. Feldman
Keyword(s):  
Nmda Receptors ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Motor Nucleus ◽  
Burst Frequency ◽  
Respiratory Network ◽  
Bath Application ◽  
Burst Amplitude ◽  
Main Column

1. The involvement of excitatory amino acid (EAA) receptors in the generation of respiratory rhythm and transmission of inspiratory drive to hypoglossal (XII) motoneurons was examined in an in vitro neonatal rat medullary slice preparation. Slices generated rhythmic inspiratory activity in XII nerves. The role of EAAs in rhythm generation was determined by analyzing perturbations of respiratory network activity after bath application of EAA receptor antagonists or local microinjection of antagonists into the main column of respiratory neurons in the ventrolateral medulla (ventral respiratory group), particularly in the pre-Botzinger complex (pre-BotC). The involvement of EAAs in drive transmission to XII motoneurons was examined by recording perturbations in XII nerve discharge or motoneuron synaptic inputs after microinjection of EAA receptor antagonists into either the XII motor nuclei or sites in the ventrolateral medulla containing interneurons of the drive transmission circuit. 2. Block of non-N-methyl-D-aspartate (non-NMDA) receptors by bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reversibly reduced XII nerve burst frequency and amplitude in a concentration-dependent manner, completely blocking respiratory motor output at concentrations > 4 microM. Activation of 2-amino-4-phosphonobutyric acid (AP-4)-sensitive receptors with D,L AP-4 reduced XII nerve burst amplitude by 30% but did not alter burst frequency. Block of NMDA receptor channels by bath application of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-iminemaleate (MK-801) did not perturb the frequency or amplitude of motor output. Inhibition of EAA uptake in the slices by bath application of dihydrokainic acid reversibly increased the frequency and amplitude of XII motor discharge. 3. Block of non-NMDA receptors at multiple sites along the main column of respiratory neurons in the ventrolateral medulla, including the pre-BotC, by unilateral microinjection of CNQX produced a dose-dependent, bilateral reduction in XII nerve burst amplitude without substantial perturbations of the frequency of respiratory oscillations. Block of non-NMDA receptors within the pre-BotC at sites ventral to amplitude altering sites produced a reduction in frequency and ultimately bilateral block of respiratory network oscillations. 4. Non-NMDA receptor block within the XII motor nucleus by unilateral microinjection of CNQX produced a dose-dependent reduction in ipsilateral XII nerve discharge amplitude without perturbing the frequency of respiratory oscillations. Perturbations of contralateral XII nerve burst amplitude were significantly smaller. NMDA channel block within the XII motor nucleus did not affect inspiratory burst amplitude, whereas activation of AP-4 receptors caused a 30% reduction in amplitude.

Identification of Two Types of Inspiratory Pacemaker Neurons in the Isolated Respiratory Neural Network of Mice

2001 ◽  
Vol 86 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Muriel Thoby-Brisson ◽  
Jan-Marino Ramirez
Keyword(s):  
Neural Network ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Pacemaker Activity ◽  
Patch Clamp Technique ◽  
Population Activity ◽  
Pacemaker Neurons ◽  
Whole Cell Patch Clamp ◽  
Respiratory Network ◽  
Bursting Activity

In the respiratory network of mice, we characterized with the whole cell patch-clamp technique pacemaker properties in neurons discharging in phase with inspiration. The respiratory network was isolated in a transverse brain stem slice containing the pre-Bötzinger complex (PBC), the presumed site for respiratory rhythm generation. After blockade of respiratory network activity with 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), 18 of 52 inspiratory neurons exhibited endogenous pacemaker activity, which was voltage dependent, could be reset by brief current injections and could be entrained by repetitive stimuli. In the pacemaker group ( n = 18), eight neurons generated brief bursts (0.43 ± 0.03 s) at a relatively high frequency (1.05 ± 0.12 Hz) in CNQX. These bursts resembled the bursts that these neurons generated in the intact network during the interval between two inspiratory bursts. Cadmium (200 μM) altered but did not eliminate this bursting activity, while 0.5 μM tetrodotoxin suppressed bursting activity. Another set of pacemaker neurons (10 of 18) generated in CNQX longer bursts (1.57 ± 0.07 s) at a lower frequency (0.35 ± 0.01 Hz). These bursts resembled the inspiratory bursts generated in the intact network in phase with the population activity. This bursting activity was blocked by 50–100 μM cadmium or 0.5 μM tetrodotoxin. We conclude that the respiratory neural network contains pacemaker neurons with two types of bursting properties. The two types of pacemaker activities might have different functions within the respiratory network.

Differential Responses of Respiratory Nuclei to Anoxia in Rhythmic Brain Stem Slices of Mice

1999 ◽  
Vol 82 (5) ◽  
pp. 2163-2170 ◽  
Author(s):  
Petra Telgkamp ◽  
Jan-Marino Ramirez
Keyword(s):  
Motor Pattern ◽  
Respiratory Control ◽  
Pattern Generation ◽  
Initial Increase ◽  
Rhythm Generation ◽  
Population Activity ◽  
Newborn Mice ◽  
Respiratory Network ◽  
Burst Amplitude ◽  
Brain Stem Slices

The response of the neonatal respiratory system to hypoxia is characterized by an initial increase in ventilation, which is followed within a few minutes by a depression of ventilation below baseline levels. We used the transverse medullary slice of newborn mice as a model system for central respiratory control to investigate the effects of short-lasting periods of anoxia. Extracellular population activity was simultaneously recorded from the ventral respiratory group (VRG) and the hypoglossus (XII) nucleus (a respiration-related motor output nucleus). During anoxia, respiratory frequency was modulated in a biphasic manner and phase-locked in both the VRG and the XII. The amplitude of phasic respiratory bursts was increased only in the XII and not in the VRG. This increase in XII burst amplitude commenced ∼1 min after the anoxic onset concomitant with a transient increase in tonic activity. The burst amplitude remained elevated throughout the entire 5 min of anoxia. Inspiratory burst amplitude in the VRG, in contrary, remained constant or even decreased during anoxia. These findings represent the first simultaneous extracellular cell population recordings of two respiratory nuclei. They provide important data indicating that rhythm generation is altered in the VRG without a concomitant alteration in the VRG burst amplitude, whereas the burst amplitude is modulated only in the XII nucleus. This has important implications because it suggests that rhythm generation and motor pattern generation are regulated separately within the respiratory network.

Hyperthermia Modulates Respiratory Pacemaker Bursting Properties

2004 ◽  
Vol 92 (5) ◽  
pp. 2844-2852 ◽  
Author(s):  
Andrew K. Tryba ◽  
Jan-Marino Ramirez
Keyword(s):  
Network Effects ◽  
Elevated Temperatures ◽  
Heat Stroke ◽  
Network Activity ◽  
Respiratory Neurons ◽  
Population Activity ◽  
Normal Body Temperature ◽  
Respiratory Network ◽  
Hyperthermic Response

Most mammals modulate respiratory frequency (RF) to dissipate heat (e.g., panting) and avoid heat stroke during hyperthermic conditions. Respiratory neural network activity recorded in an isolated brain stem-slice preparation of mice exhibits a similar RF modulation in response to hyperthermia; fictive eupneic frequency increases while inspiratory network activity amplitude and duration are significantly reduced. Here, we study the effects of hyperthermia on the activity of synaptically isolated respiratory pacemakers to examine the possibility that these changes may account for the hyperthermic RF modulation of the respiratory network. During heating, modulation of the bursting frequency of synaptically isolated pacemakers paralleled that of population bursting recorded from the intact network, whereas nonpacemaker neurons were unaffected, suggesting that pacemaker bursting may account for the temperature-enhanced RF observed at the network level. Some respiratory neurons that were tonically active at hypothermic conditions exhibited pacemaker properties at approximately the normal body temperature of eutherian mammals (36.81 ± 1.17°C; mean ± SD) and continued to burst at 40°C. At elevated temperatures (40°C), there was an enhancement of the depolarizing drive potential in synaptically isolated pacemakers, while the amplitude of integrated population activity declined. Isolated pacemaker bursting ceased at 41–42°C ( n = 5), which corresponds to temperatures at which hyperthermic-apnea typically occurs in vivo. We conclude that pacemaker properties may play an important role in the hyperthermic frequency modulation and apnea, while network effects may play important roles in generating other aspects of the hyperthermic response, such as the decreased amplitude of ventral respiratory group activity during hyperthermia.

TEMPERATURE REGULATION IN EXERCISE

PEDIATRICS ◽  
1963 ◽  
Vol 32 (4) ◽  
pp. 691-702
Author(s):  
Sid Robinson
Keyword(s):  
Blood Flow ◽  
Body Temperature ◽  
Heat Stroke ◽  
The Body ◽  
Physiological Regulation ◽  
Temperature Changes ◽  
Metabolic Heat ◽  
Warm Blood ◽  
Hot Environments ◽  
Large Increments

The central body temperature of a man rises gradually during the first half hour of a period of work to a higher level and this level is precisely maintained until the work is stopped; body temperature then slowly declines to the usual resting level. During prolonged work the temperature regulatory center in the hypothalamus appears to be reset at a level which is proportional to the intensity of the work and this setting is independent of environmental temperature changes ranging from cold to moderately warm. In hot environments the resistance to heat loss may be so great that all of the increased metabolic heat of work cannot be dissipated and the man's central temperature will rise above the thermostatic setting. If this condition of imbalance is continued long enough heat stroke will ensue. We have found that in a 3 mile race lasting only 14 minutes on a hot summer day a runner's rectal temperature may rise to 41.1°C., with heat stroke imminent. The physiological regulation of body temperature of men in warm environments and during the increased metabolic heat production of work is dependent on sweating to provide evaporative cooling of the skin, and on adjustments of cutaneous blood flow which determine the conductance of heat from the deeper tissues to the skin. The mechanisms of regulating these responses during work are complex and not entirely understood. Recent experiments carried out in this laboratory indicate that during work, sweating may be regulated by reflexes originating from thermal receptors in the veins draining warm blood from the muscles, summated with reflexes from the cutaneous thermal receptors, both acting through the hypothalamic center, the activity of which is increased in proportion to its own temperature. At the beginning of work the demand for blood flow to the muscles results in reflex vasoconstriction in the skin. As the body temperature rises the thermal demand predominates and the cutaneous vessels dilate, increasing heat conductance to the skin. Large increments in cardiac output and compensatory vasoconstriction in the abdominal viscera make these vascular adjustments in work possible without circulatory embarrassment.

Amplitude and Direction of Saccadic Eye Movements Depend on the Synchronicity of Collicular Population Activity

2004 ◽  
Vol 92 (1) ◽  
pp. 424-432 ◽  
Author(s):  
Michael Brecht ◽  
Wolf Singer ◽  
Andreas K. Engel
Keyword(s):  
Eye Movements ◽  
Saccadic Eye Movements ◽  
Brain Structures ◽  
High Temporal Resolution ◽  
Temporal Relations ◽  
Neuronal Responses ◽  
Population Activity ◽  
Neuronal Processing ◽  
The Individual ◽  
Cat Superior Colliculus

Synchronization of neuronal discharges has been observed in numerous brain structures, but opinions diverge regarding its significance in neuronal processing. Here we investigate whether the motion vectors of saccadic eye movements evoked by electrical multisite stimulation of the cat superior colliculus (SC) are influenced by varying the degree of synchrony between the stimulus trains. With synchronous activation of SC sites, the vectors of the resulting saccades correspond approximately to the averages of the vectors of saccades evoked from each site alone. In contrast, when the pulses of trains applied to the different sites are temporally offset by as little as 5–10 ms, the vectors of the resulting saccades come close to the sum of the individual vectors. Thus saccade vectors depend not only on the site and amplitude of collicular activation but also on the precise temporal relations among the respective spike trains. These data indicate that networks within or downstream from the SC discriminate with high temporal resolution between synchronous and asynchronous population responses. This supports the hypothesis that information is encoded not only in the rate of neuronal responses but also in the precise temporal relations between discharges.

scholarly journals Reversible hierarchical structure induced by solvation and temperature modulation in an ionic liquid-based random bottlebrush copolymer

2018 ◽  
Vol 9 (42) ◽  
pp. 5200-5214 ◽  
Author(s):  
Harsha D. Magurudeniya ◽  
Bryan S. Ringstrand ◽  
Sönke Seifert ◽  
Millicent A. Firestone
Keyword(s):  
Ionic Liquid ◽  
Hierarchical Structure ◽  
Temperature Modulation ◽  
Temperature Changes ◽  
Poly Ionic Liquid

Discoidal bottlebrush poly(ionic liquid)s are reversibly stacked into 1-D rod like assembles by temperature changes.

scholarly journals Imaging of respiratory-related population activity with single-cell resolution

2007 ◽  
Vol 292 (1) ◽  
pp. C508-C516 ◽  
Author(s):  
Frank Funke ◽  
Mathias Dutschmann ◽  
Michael Müller
Keyword(s):  
Single Cell ◽  
Neuronal Activity ◽  
Single Cells ◽  
Activity Patterns ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Population Activity ◽  
Respiratory Network

The pre-Bötzinger complex (PBC) in the rostral ventrolateral medulla contains a kernel involved in respiratory rhythm generation. So far, its respiratory activity has been analyzed predominantly by electrophysiological approaches. Recent advances in fluorescence imaging now allow for the visualization of neuronal population activity in rhythmogenic networks. In the respiratory network, voltage-sensitive dyes have been used mainly, so far, but their low sensitivity prevents an analysis of activity patterns of single neurons during rhythmogenesis. We now have succeeded in using more sensitive Ca2+ imaging to study respiratory neurons in rhythmically active brain stem slices of neonatal rats. For the visualization of neuronal activity, fluo-3 was suited best in terms of neuronal specificity, minimized background fluorescence, and response magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar treatment (100 mM mannitol) during dye loading. Rhythmic population activity was imaged with single-cell resolution using a sensitive charge-coupled device camera and a ×20 objective, and it was correlated with extracellularly recorded mass activity of the contralateral PBC. Correlated optical neuronal activity was obvious online in 29% of slices. Rhythmic neurons located deeper became detectable during offline image processing. Based on their activity patterns, 74% of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons. Our approach is well suited to visualize and correlate the activity of several single cells with respiratory network activity. We demonstrate that neuronal synchronization and possibly even network configurations can be analyzed in a noninvasive approach with single-cell resolution and at frame rates currently not reached by most scanning-based imaging techniques.

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