To model or not to model – the physiologist's dilemma DOI Open Access
Christopher G. Wilson

The Journal of Physiology, Год журнала: 2020, Номер 598(21), С. 4747 - 4748

Опубликована: Сен. 9, 2020

We live in a time of ubiquitous computational convenience, meaning that computers are everywhere and useful for our needs as physiologists. have far more powerful than those took mankind to the moon we carry them upon person every day form cell phones laptops. Even common phone can be used simulation neurons simple neural networks (Dragly et al. 2017). Physiologists been taking advantage this kind power decades now – journal Hodgkin Huxley published first model neuron (Hodgkin & Huxley, 1952) revolutionized way approach neurophysiology. Within community investigators focused on respiratory physiology breathing control, many us use hybrid computation experiment drive work improve understanding brainstem network. (For comprehensive review these models, see Lindsey colleagues’ highlights approaches over past 60 years; 2012.) In issue The Journal Physiology, Flor (2020) present role Bötzinger complex play generation active expiration. Their paper is an excellent exemplar synthesis experimental work, showcasing physiological networks. Here, authors developed informed by extensive recordings from decerebrate, arterially perfused situ preparations juvenile rats. They recorded whole nerves single (extracellularly) correlate activity with phase exposure hypercapnia hypoxia. tested hypothesis inhibitory projections parafacial group (pFRG) control emergence expiration conditions elevated drive. These experiments provide necessary information about inhibition plays stabilizing transitions inspiration. interplay between expiratory inspiratory network ongoing focus research within field. few years, there has concentrated pFRG its interactions preBötzinger complexes. found contraction abdominal muscles at end during metabolic challenges (hypercapnia hypoxia) improves pulmonary ventilation. pattern requires recruitment pFRG. Additionally, they show important source oscillator. GABAergic glycinergic synapses oscillator under resting condition while modulating then perform simulations closely matched data their experiments. This combined modelling informs organization connections network, particularly regard expiration, which not subject such theoretical before. colleagues shown value closing feedback loop theory develop predictive refine illustrates salient point: bar entry using mathematical models lower ever access tools robust much user friendly writing own FORTRAN or C/C++ code (though chose write C++). Simulation environments like NEURON (https://neuron.yale.edu/neuron/), Brian (https://briansimulator.org/), MCell (https://mcell.org/) all foundation investigator begin purposes. if one chooses one's ModelDB (https://senselab.med.yale.edu/modeldb/) database adapted laboratory. make it possible to, relatively easily, build theoretical–experimental maximize efficiency cost-effectiveness While no perfectly captures subtlety cellular physiology, her team done job testing real physiology. serves blueprint world strive integrate new concepts ‘burstlet theory’ (Kallurkar 2020) massively parallel high performance clusters real-time neurophysiological work. None. Sole author.

Язык: Английский

Breathing Rhythm and Pattern and Their Influence on Emotion DOI Open Access
Sufyan Ashhad, Kaiwen Kam, Christopher A. Del Negro

и другие.

Annual Review of Neuroscience, Год журнала: 2022, Номер 45(1), С. 223 - 247

Опубликована: Март 9, 2022

Breathing is a vital rhythmic motor behavior with surprisingly broad influence on the brain and body. The apparent simplicity of breathing belies complex neural control system, central pattern generator (bCPG), that exhibits diverse operational modes to regulate gas exchange coordinate an array behaviors. In this review, we focus selected advances in our understanding bCPG. At core bCPG preBötzinger (preBötC), which drives inspiratory rhythm via unexpectedly sophisticated emergent mechanism. Synchronization dynamics underlying preBötC rhythmogenesis imbue system robustness lability. These are modulated by inputs from throughout generate rhythmic, patterned activity widely distributed. connectivity emerging literature support link between breathing, emotion, cognition becoming experimentally tractable. bring great potential for elucidating function dysfunction other mammalian circuits.

Язык: Английский

Процитировано

91
The integrated brain network that controls respiration DOI Creative Commons
Friedrich Krohn, Manuele Novello, Ruben S. van der Giessen

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 8, 2023

Respiration is a brain function on which our lives essentially depend. Control of respiration ensures that the frequency and depth breathing adapt continuously to metabolic needs. In addition, respiratory control network has organize muscular synergies integrate ventilation with posture body movement. Finally, coupled cardiovascular emotion. Here, we argue can handle this all by integrating brainstem central pattern generator circuit in larger also comprises cerebellum. Although currently not generally recognized as center, cerebellum well known for its coordinating modulating role motor behavior, autonomic nervous system. review, discuss regions involved respiration, their anatomical functional interactions. We how sensory feedback result adaptation these mechanisms be compromised various neurological psychological disorders. demonstrate generators are part integrated regions.

Язык: Английский

Процитировано

84
Advancing respiratory–cardiovascular physiology with the working heart–brainstem preparation over 25 years DOI Creative Commons
Julian F. R. Paton, Benedito H. Machado, Davi J. A. Moraes

и другие.

The Journal of Physiology, Год журнала: 2022, Номер 600(9), С. 2049 - 2075

Опубликована: Март 16, 2022

Abstract Twenty‐five years ago, a new physiological preparation called the working heart–brainstem (WHBP) was introduced with claim it would provide platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of progress made WHBP, advantages disadvantages along potential future applications, photographs technical drawings all customised equipment used for preparation. Using mice or rats, WHBP is an situ experimental model that perfused via extracorporeal circuit benefitting from unprecedented surgical access, mechanical stability brain whole cell recording uncompromised use pharmacological agents akin to vitro approaches. The has revealed novel mechanistic insights into, example, generation distinct rhythms, neurogenesis sympathetic activity, coupling between respiration heart circulation, hypothalamic spinal control mechanisms, peripheral central chemoreceptor mechanisms. Insights have been gleaned into diseases such as hypertension, failure sleep apnoea. Findings ratified conscious vivo animals when tested translated humans. We conclude by discussing applications including two‐photon imaging nervous systems adoption pharmacogenetic tools will improve our understanding mechanisms reveal may guide treatment strategies cardiorespiratory diseases. image

Язык: Английский

Процитировано

38
Role of the postinspiratory complex in regulating swallow–breathing coordination and other laryngeal behaviors DOI Creative Commons
Alyssa Huff, Marlusa Karlen‐Amarante, Luíz M. Oliveira

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Июнь 5, 2023

Breathing needs to be tightly coordinated with upper airway behaviors, such as swallowing. Discoordination leads aspiration pneumonia, the leading cause of death in neurodegenerative disease. Here, we study role postinspiratory complex (PiCo) coordinating breathing and Using optogenetic approaches freely anesthetized ChATcre:Ai32, Vglut2cre:Ai32 intersectional recombination ChATcre:Vglut2FlpO:ChR2 mice reveals PiCo mediates protective behaviors. Activation during inspiration or beginning postinspiration triggers swallow behavior an all-or-nothing manner, while there is a higher probability for stimulating only laryngeal activation when activated further into expiration. Laryngeal dependent on stimulation duration. Sufficient bilateral necessary preserving physiological motor sequence since few neurons unilateral blurred behavioral responses. We believe acts interface between pattern generator preBötzinger coordinate breathing. Investigating PiCo’s coordination will aid understanding discoordination neurological diseases.

Язык: Английский

Процитировано

23
Central respiratory chemoreception DOI
Patrice G. Guyenet, Douglas A. Bayliss

Handbook of clinical neurology, Год журнала: 2022, Номер unknown, С. 37 - 72

Опубликована: Янв. 1, 2022

Язык: Английский

Процитировано

27
Anatomical distribution of µ-opioid receptors, neurokinin-1 receptors, and vesicular glutamate transporter 2 in the mouse brainstem respiratory network DOI

Andreea Furdui,

Carolina da Silveira Scarpellini, Gaspard Montandon

и другие.

Journal of Neurophysiology, Год журнала: 2024, Номер 132(1), С. 108 - 129

Опубликована: Май 15, 2024

Opioid drugs can cause serious respiratory side-effects by binding to µ-opioid receptors (MORs) in brainstem regions that control breathing. To better understand the and their cellular subpopulations may be vulnerable modulation opioids, we provide a comprehensive map of Oprm1 (gene encoding MORs) mRNA expression throughout modulate Notably, identify glutamatergic neurokinin-1 receptor-expressing cells as potentially opioid worthy further investigation using targeted approaches.

Язык: Английский

Процитировано

6
Differential Contribution of the Retrotrapezoid Nucleus and C1 Neurons to Active Expiration and Arousal in Rats DOI Creative Commons
George M. P. R. Souza, Ruth L. Stornetta, Daniel S. Stornetta

и другие.

Journal of Neuroscience, Год журнала: 2020, Номер 40(45), С. 8683 - 8697

Опубликована: Сен. 24, 2020

Collectively, the retrotrapezoid nucleus (RTN) and adjacent C1 neurons regulate breathing, circulation state of vigilance, but previous methods to manipulate activity these have been insufficiently selective parse out their relative roles. We hypothesize that RTN distinct aspects breathing (e.g., frequency, amplitude, active expiration, sighing) differ in ability produce arousal from sleep. Here we use optogenetics a combination viral vectors adult male female Th -Cre rats transduce selectively (Phox2b + /Nmb ) or / with Channelrhodopsin-2. photostimulation modestly increased probability arousal. stimulation robustly frequency amplitude; it also triggered strong expiration not sighs. Consistent responses, innervates entire pontomedullary respiratory network, including expiratory premotor caudal ventral group, has very limited projections brainstem regions (locus ceruleus, CGRP parabrachial neurons). neuron produced robust arousals similar increases amplitude compared stimulation, sighs were elicited was absent. Unlike RTN, innervate locus processes within complex, lack group. In sum, stimulating activates robustly, only produces consistent role as central chemoreceptors. Conversely, strongly stimulates ascending systems sighs, postulated acute stress responses. SIGNIFICANCE STATEMENT The reside rostral ventrolateral medulla. Both cardiovascular system ways are unclear because technical limitations (anesthesia, nonselective neuronal actuators). Using unanesthetized rats, found either breathing. However, triggers presumably unlike C1, direct excitatory abdominal neurons. potential is far greater than however, C1's wake-promoting structures. short, orchestrate cardiorespiratory responses somatic stresses, whereas controls lung ventilation arterial P co 2 stability.

Язык: Английский

Процитировано

36
Mapping of the excitatory, inhibitory, and modulatory afferent projections to the anatomically defined active expiratory oscillator in adult male rats DOI
Vivian Biancardi, Jashan Saini,

Anileen Pageni

и другие.

The Journal of Comparative Neurology, Год журнала: 2020, Номер 529(4), С. 853 - 884

Опубликована: Июль 13, 2020

Abstract The lateral parafacial region (pF L ; which encompasses the respiratory group, pFRG) is a conditional oscillator that drives active expiration during periods of high demand, and increases ventilation through recruitment expiratory muscles. pF activity highly modulated, systematic analysis its afferent projections required to understand connectivity modulatory control. We combined viral retrograde tracing approach map direct brainstem putative location , with RNAScope immunofluorescence identify neurochemical phenotype projecting neurons. Within medulla, retrogradely‐labeled, glutamatergic, glycinergic GABAergic neurons were found in ventral column (Bötzinger preBötzinger Complex [preBötC], [pF V ] ), nucleus solitary tract (NTS), reticular formation (RF), pontine midbrain vestibular nuclei, medullary raphe. In pons midbrain, retrogradely‐labeled same phenotypes Kölliker‐Fuse parabrachial periaqueductal gray, pedunculopontine (PPT) laterodorsal tegmentum (LDT). also identified somatostatin‐expressing preBötC PHOX2B immunopositive cells NTS, part RF. Surprisingly, we no catecholaminergic A5 or Locus Coeruleus serotoninergic raphe nor any cholinergic PPT LDT projected . Our results indicate receive extensive excitatory inhibitory inputs from several nonrespiratory related regions could contribute complex modulation for expiration.

Язык: Английский

Процитировано

30
Respiratory rhythm and pattern generation: Brainstem cellular and circuit mechanisms DOI
Jeffrey C. Smith

Handbook of clinical neurology, Год журнала: 2022, Номер unknown, С. 1 - 35

Опубликована: Янв. 1, 2022

Язык: Английский

Процитировано

17
Supraspinal glycinergic neurotransmission in pain: A scoping review of current literature DOI Creative Commons
Caitlin Fenech, Bryony L. Winters, Yo Otsu

и другие.

Journal of Neurochemistry, Год журнала: 2024, Номер 168(11), С. 3663 - 3684

Опубликована: Июль 29, 2024

The neurotransmitter glycine is an agonist at the strychnine-sensitive receptors. In addition, it has recently been discovered to act two new receptors, excitatory receptor and metabotropic receptor. Glycine's roles have most extensively investigated in spinal cord, where known play essential pain, itch, motor function. contrast, less about supraspinal glycinergic functions, their contributions pain circuits are largely unrecognized. As neurons absent from cortical regions, a clearer understanding of how modulates could reveal pharmacological targets. This review aims synthesize published research on glycine's role adult brain, highlighting regions signaling may modulate responses. was achieved through scoping methodology identifying several key circuitry involved. Therefore, this unveils critical gaps for potential pain-associated responses, encouraging researchers consider neurotransmission more widely when investigating neural mechanisms pain.

Язык: Английский

Процитировано

4