scholarly journals Differential Modulation of Neural Network and Pacemaker Activity Underlying Eupnea and Sigh-Breathing Activities

2008 ◽  
Vol 99 (5) ◽  
pp. 2114-2125 ◽  
Author(s):  
Andrew K. Tryba ◽  
Fernando Peña ◽  
Steven P. Lieske ◽  
Jean-Charles Viemari ◽  
Muriel Thoby-Brisson ◽  
...  
Keyword(s):  
Low Frequency ◽  
Network Activity ◽  
Pacemaker Activity ◽  
Differential Modulation ◽  
Multiple Frequency ◽  
Low Frequencies ◽  
Respiratory Network ◽  
Bötzinger Complex ◽  
Amplitude Characteristics

Many networks generate distinct rhythms with multiple frequency and amplitude characteristics. The respiratory network in the pre-Bötzinger complex (pre-Böt) generates both the low-frequency, large-amplitude sigh rhythm and a faster, smaller-amplitude eupneic rhythm. Could the same set of pacemakers generate both rhythms? Here we used an in vitro respiratory brainslice preparation. We describe a subset of synaptically isolated pacemakers that spontaneously generate two distinct bursting patterns. These two patterns resemble network activity including sigh-like bursts that occur at low frequencies and have large amplitudes and eupneic-like bursts with higher frequency and smaller amplitudes. Cholinergic neuromodulation altered the network and pacemaker bursting: fictive sigh frequency is increased dramatically, whereas fictive eupneic frequency is drastically lowered. The data suggest that timing and amplitude characteristics of fictive eupneic and sigh rhythms are set by the same set of pacemakers that are tuned by changes in the neuromodulatory state.

scholarly journals CT2A Cell Viability Modulated by Electromagnetic Fields at Extremely Low Frequency under No Thermal Effects

2019 ◽  
Vol 21 (1) ◽  
pp. 152 ◽  
Author(s):  
Olga García-Minguillán ◽  
Raquel Prous ◽  
Maria del Carmen Ramirez-Castillejo ◽  
Ceferino Maestú
Keyword(s):  
Cell Viability ◽  
Frequency Dependence ◽  
Electromagnetic Fields ◽  
Thermal Effects ◽  
Low Frequency ◽  
Human Beings ◽  
Cellular Mechanisms ◽  
Low Frequencies ◽  
Hsp90 Expression

The effects produced by electromagnetic fields (EMFs) on human beings at extremely low frequencies (ELFs) have being investigated in the past years, across in vitro studies, using different cell lines. Nevertheless, the effects produced on cells are not clarified, and the cellular mechanisms and cell-signaling processes involved are still unknown. This situation has resulted in a division among the scientific community about the adequacy of the recommended level of exposure. In this sense, we consider that it is necessary to develop long-term exposure studies and check if the recommended levels of EMFs are under thermal effects. Hence, we exposed CT2A cells to different EMFs at different ELFs at short and long times. Our results showed frequency dependence in CT2A exposed during 24 h to a small EMF of 30 μT equal to those originated by the Earth and frequency dependence after the exposure during seven days to an EMF of 100 µT at different ELFs. Particularly, our results showed a remarkable cell viability decrease of CT2A cells exposed to EMFs of 30 Hz. Nevertheless, after analyzing the thermal effects in terms of HSP90 expression, we did not find thermal damages related to the differences in cell viability, so other crucial cellular mechanism should be involved.

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.

Norepinephrine Differentially Modulates Different Types of Respiratory Pacemaker and Nonpacemaker Neurons

2006 ◽  
Vol 95 (4) ◽  
pp. 2070-2082 ◽  
Author(s):  
Jean-Charles Viemari ◽  
Jan-Marino Ramirez
Keyword(s):  
Frequency Modulation ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Flufenamic Acid ◽  
Pacemaker Activity ◽  
Rhythm Generation ◽  
Burst Frequency ◽  
Pacemaker Neurons ◽  
Respiratory Network ◽  
Different Types

Pacemakers are found throughout the mammalian CNS. Yet, it remains largely unknown how these neurons contribute to network activity. Here we show that for the respiratory network isolated in transverse slices of mice, different functions can be assigned to different types of pacemakers and nonpacemakers. This difference becomes evident in response to norepinephrine (NE). Although NE depolarized 88% of synaptically isolated inspiratory neurons, this neuromodulator had differential effects on different neuron types. NE increased in cadmium-insensitive pacemakers burst frequency, not burst area and duration, and it increased in cadmium-sensitive pacemakers burst duration and area, but not frequency. NE also differentially modulated nonpacemakers. Two types of nonpacemakers were identified: “silent nonpacemakers” stop spiking, whereas “active nonpacemakers” spontaneously spike when isolated from the network. NE selectively induced cadmium-sensitive pacemaker properties in active, but not silent, nonpacemakers. Flufenamic acid (FFA), a blocker of ICAN, blocked the induction as well as modulation of cadmium-sensitive pacemaker activity, and blocked at the network level the NE-induced increase in burst area and duration of inspiratory network activity; the frequency modulation (FM) was unaffected. We therefore propose that modulation of cadmium-sensitive pacemaker activity contributes at the network level to changes in burst shape, not frequency. Riluzole blocked the FM of isolated cadmium-insensitive pacemakers. In the presence of riluzole, NE caused disorganized network activity, suggesting that cadmium-insensitive pacemakers are critical for rhythm generation. We conclude that different types of nonpacemaker and pacemaker neurons differentially control different aspects of the respiratory rhythm.

scholarly journals Physiology and anatomy of neurons in the medial superior olive of the mouse

2016 ◽  
Vol 116 (6) ◽  
pp. 2676-2688 ◽  
Author(s):  
Matthew J. Fischl ◽  
R. Michael Burger ◽  
Myriam Schmidt-Pauly ◽  
Olga Alexandrova ◽  
James L. Sinclair ◽  
...  
Keyword(s):  
Sound Localization ◽  
Molecular Mechanisms ◽  
Low Frequency ◽  
Acoustic Stimulation ◽  
Medial Superior Olive ◽  
Temporal Acuity ◽  
Low Frequencies ◽  
Superior Olive

In mammals with good low-frequency hearing, the medial superior olive (MSO) computes sound location by comparing differences in the arrival time of a sound at each ear, called interaural time disparities (ITDs). Low-frequency sounds are not reflected by the head, and therefore level differences and spectral cues are minimal or absent, leaving ITDs as the only cue for sound localization. Although mammals with high-frequency hearing and small heads (e.g., bats, mice) barely experience ITDs, the MSO is still present in these animals. Yet, aside from studies in specialized bats, in which the MSO appears to serve functions other than ITD processing, it has not been studied in small mammals that do not hear low frequencies. Here we describe neurons in the mouse brain stem that share prominent anatomical, morphological, and physiological properties with the MSO in species known to use ITDs for sound localization. However, these neurons also deviate in some important aspects from the typical MSO, including a less refined arrangement of cell bodies, dendrites, and synaptic inputs. In vitro, the vast majority of neurons exhibited a single, onset action potential in response to suprathreshold depolarization. This spiking pattern is typical of MSO neurons in other species and is generated from a complement of Kv1, Kv3, and IH currents. In vivo, mouse MSO neurons show bilateral excitatory and inhibitory tuning as well as an improvement in temporal acuity of spiking during bilateral acoustic stimulation. The combination of classical MSO features like those observed in gerbils with more unique features similar to those observed in bats and opossums make the mouse MSO an interesting model for exploiting genetic tools to test hypotheses about the molecular mechanisms and evolution of ITD processing.

Long-Term Modulation of Respiratory Network Activity Following Anoxia In Vitro

2002 ◽  
Vol 87 (6) ◽  
pp. 2964-2971 ◽  
Author(s):  
Dawn M. Blitz ◽  
Jan-Marino Ramirez
Keyword(s):  
Respiratory Frequency ◽  
Network Activity ◽  
Oxygen Level ◽  
Frequency Increase ◽  
Respiratory Network ◽  
Temporary Decrease ◽  
Rhythmic Behaviors ◽  
Lasting Influence

Neural networks that produce rhythmic behaviors require flexibility to respond to changes in the internal and external state of the animal. It is important to not only understand how a network responds during such perturbations but also how the network recovers. For example, the respiratory network needs to respond to and recover from temporary changes in oxygen level that can occur during sleep, exercise, and respiratory disorders. During a temporary decrease in oxygen level, there is an increase in respiratory frequency followed by a depression that can lead to complete apnea. Here we used a mouse brain stem slice preparation as a model system to examine the recovery of respiratory network activity after brief episodes of anoxia. We found the respiratory network recovers from a single anoxic episode with a transient increase in fictive respiratory frequency. Although repetitive anoxia does not elicit a greater frequency increase, it does elicit a longer lasting frequency increase persisting ≤90 min. Thus there is a centrally mediated long-lasting influence on the respiratory network elicited by decreased oxygen levels. This modulation occurs as a prolonged facilitation of fictive respiratory frequency after brief repetitive but not single anoxic exposure. These data are important to consider in the context of disorders such as sleep apnea in which brief periodic anoxic episodes are experienced.

scholarly journals Graded Reductions in Oxygenation Evoke Graded Reconfiguration of the Isolated Respiratory Network

2011 ◽  
Vol 105 (2) ◽  
pp. 625-639 ◽  
Author(s):  
Andrew A. Hill ◽  
Alfredo J. Garcia ◽  
Sebastien Zanella ◽  
Ridhdhi Upadhyaya ◽  
Jan Marino Ramirez
Keyword(s):  
Oxidative Stress ◽  
Tissue Oxygenation ◽  
Control Of Breathing ◽  
Network Activity ◽  
Central Control ◽  
Respiratory Network ◽  
Bötzinger Complex ◽  
Network Output ◽  
Brain Stem Slices ◽  
Stem Slices

Neurons depend on aerobic metabolism, yet are very sensitive to oxidative stress and, as a consequence, typically operate in a low O2 environment. The balance between blood flow and metabolic activity, both of which can vary spatially and dynamically, suggests that local O2 availability markedly influences network output. Yet the understanding of the underlying O2-sensing mechanisms is limited. Are network responses regulated by discrete O2-sensing mechanisms or, rather, are they the consequence of inherent O2 sensitivities of mechanisms that generate the network activity? We hypothesized that a broad range of O2 tensions progressively modulates network activity of the pre-Bötzinger complex (preBötC), a neuronal network critical to the central control of breathing. Rhythmogenesis was measured from the preBötC in transverse neonatal mouse brain stem slices that were exposed to graded reductions in O2 between 0 and 95% O2, producing tissue oxygenation values ranging from 20 ± 18 (mean ± SE) to 440 ± 56 Torr at the slice surface, respectively. The response of the preBötC to graded changes in O2 is progressive for some metrics and abrupt for others, suggesting that different aspects of the respiratory network have different sensitivities to O2.

Pepsinogen secretion: coupling of exocytosis visualized by video microscopy and [Ca2+]iin single cells

1998 ◽  
Vol 274 (6) ◽  
pp. G1166-G1177 ◽  
Author(s):  
Chie Tao ◽  
Masao Yamamoto ◽  
Hiroshi Mieno ◽  
Masaki Inoue ◽  
Tsutomu Masujima ◽  
...  
Keyword(s):  
Cellular Response ◽  
Single Cells ◽  
Critical Role ◽  
Low Frequency ◽  
Close Relation ◽  
Low Frequencies ◽  
Low Concentrations ◽  
Pepsinogen Secretion ◽  
Initial Peak

Conventional in vitro studies of pepsinogen secretion have measured secretion into the bulk medium and have demonstrated the critical role of Ca2+ in the process. The present study was undertaken to obtain further details of the process of secretion and its relation to Ca2+changes over very short time periods. The relation between Ca2+ mobilization and exocytosis in an isolated individual peptic cell of the bullfrog was investigated by a method to measure both intracellular Ca2+([Ca2+]i), using a fluorescent Ca2+indicator, fura 2, and exocytosis from single cells using a video microscope analyzing system. Bombesin (3.2 × 10−7 M) and bethanechol (3.2 × 10−4 M) caused a rapid increase in [Ca2+]i(initial peak) and a corresponding high frequency of initial exocytosis. After the initial peak, [Ca2+]iwas maintained at a somewhat elevated level over the baseline (sustained phase), with a corresponding low frequency of exocytosis. Both the sustained phase of elevated [Ca2+]iand the related exocytosis were eliminated by the depletion of extracellular Ca2+. Low concentrations of bombesin (3.2 × 10−10 M) and bethanechol (3.2 × 10−7 M) caused sustained low-amplitude Ca2+oscillations with correspondingly low frequencies but also caused sustained exocytosis. These data show that 1) cellular response differs between high and low concentrations of stimulus, 2) there is a close relation between [Ca2+]iand exocytosis, 3) exocytosis follows elevation of [Ca2+]iby 14–45 s ( n = 6), and 4) there is a significant positive correlation between the peak [Ca2+]iand the number of exocytoses.

scholarly journals Different roles for inhibition in the rhythm-generating respiratory network

2017 ◽  
Vol 118 (4) ◽  
pp. 2070-2088 ◽  
Author(s):  
Kameron Decker Harris ◽  
Tatiana Dashevskiy ◽  
Joshua Mendoza ◽  
Alfredo J. Garcia ◽  
Jan-Marino Ramirez ◽  
...  
Keyword(s):  
Long Range ◽  
Biophysical Model ◽  
Two Phase ◽  
Adverse Conditions ◽  
Local Inhibition ◽  
Respiratory Network ◽  
Bötzinger Complex ◽  
The Stability ◽  
Rhythmic Behaviors

Unraveling the interplay of excitation and inhibition within rhythm-generating networks remains a fundamental issue in neuroscience. We use a biophysical model to investigate the different roles of local and long-range inhibition in the respiratory network, a key component of which is the pre-Bötzinger complex inspiratory microcircuit. Increasing inhibition within the microcircuit results in a limited number of out-of-phase neurons before rhythmicity and synchrony degenerate. Thus unstructured local inhibition is destabilizing and cannot support the generation of more than one rhythm. A two-phase rhythm requires restructuring the network into two microcircuits coupled by long-range inhibition in the manner of a half-center. In this context, inhibition leads to greater stability of the two out-of-phase rhythms. We support our computational results with in vitro recordings from mouse pre-Bötzinger complex. Partial excitation block leads to increased rhythmic variability, but this recovers after blockade of inhibition. Our results support the idea that local inhibition in the pre-Bötzinger complex is present to allow for descending control of synchrony or robustness to adverse conditions like hypoxia. We conclude that the balance of inhibition and excitation determines the stability of rhythmogenesis, but with opposite roles within and between areas. These different inhibitory roles may apply to a variety of rhythmic behaviors that emerge in widespread pattern-generating circuits of the nervous system. NEW & NOTEWORTHY The roles of inhibition within the pre-Bötzinger complex (preBötC) are a matter of debate. Using a combination of modeling and experiment, we demonstrate that inhibition affects synchrony, period variability, and overall frequency of the preBötC and coupled rhythmogenic networks. This work expands our understanding of ubiquitous motor and cognitive oscillatory networks.

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