Breathing Rhythm and Pattern and Their Influence on Emotion

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

---

The Dynamic Basis of Respiratory Rhythm Generation: One Breath at a Time

Annual Review of Neuroscience, Год журнала: 2018, Номер 41(1), С. 475 - 499

Опубликована: Май 1, 2018

Rhythmicity is a universal timing mechanism in the brain, and rhythmogenic mechanisms are generally dynamic. This illustrated for neuronal control of breathing, behavior that occurs as one-, two-, or three-phase rhythm. Each breath assembled stochastically, increasing evidence suggests each phase can be generated independently by dedicated excitatory microcircuit. Within microcircuit, rhythmicity emerges through three entangled mechanisms: ( a) glutamatergic transmission, which amplified b) intrinsic bursting opposed c) concurrent inhibition. triangle dynamically tuned neuromodulators other network interactions. The ability coupled oscillators to reconfigure recombine may allow breathing remain robust yet plastic enough conform nonventilatory behaviors such vocalization, swallowing, coughing. Lessons learned from respiratory translate highly dynamic integrated rhythmic systems, if approached one at time.

Язык: Английский

---

Understanding and countering opioid‐induced respiratory depression

British Journal of Pharmacology, Год журнала: 2021, Номер 180(7), С. 813 - 828

Опубликована: Июнь 5, 2021

Respiratory depression is the proximal cause of death in opioid overdose, yet mechanisms underlying this potentially fatal outcome are not well understood. The goal review to provide a comprehensive understanding pharmacological opioid‐induced respiratory depression, which could lead improved therapeutic options counter as other detrimental effects opioids on breathing. development tolerance system also discussed, differences degree caused by various agonists. Finally, potential future agents aimed at reversing or avoiding through non‐opioid receptor targets and certain advantages over naloxone. By providing an overview network, will benefit research countering depression. LINKED ARTICLES This article part themed issue Advances Opioid Pharmacology Time Epidemic. To view articles section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc

Язык: Английский

---

Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network

eLife, Год журнала: 2021, Номер 10

Опубликована: Авг. 17, 2021

The analgesic utility of opioid-based drugs is limited by the life-threatening risk respiratory depression. Opioid-induced depression (OIRD), mediated μ-opioid receptor (MOR), characterized a pronounced decrease in frequency and regularity inspiratory rhythm, which originates from medullary preBötzinger Complex (preBötC). To unravel cellular- network-level consequences MOR activation preBötC, MOR-expressing neurons were optogenetically identified manipulated transgenic mice vitro vivo. Based on these results, model OIRD was developed silico. We conclude that hyperpolarization - expressing preBötC alone does not phenocopy OIRD. Instead, effects are twofold: (1) pre-inspiratory spiking reduced (2) excitatory synaptic transmission suppressed, thereby disrupting network-driven rhythmogenesis. These dual mechanisms opioid action act synergistically to make normally robust rhythm-generating network particularly prone collapse when challenged with exogenous opioids.

Язык: Английский

---

Bursting in a next generation neural mass model with synaptic dynamics: a slow–fast approach

Nonlinear Dynamics, Год журнала: 2022, Номер 108(4), С. 4261 - 4285

Опубликована: Апрель 19, 2022

Abstract We report a detailed analysis on the emergence of bursting in recently developed neural mass model that includes short-term synaptic plasticity. Neural models can mimic collective dynamics large-scale neuronal populations terms few macroscopic variables like mean membrane potential and firing rate. The present one is particularly important, as it represents an exact meanfield limit synaptically coupled quadratic integrate fire (QIF) neurons. Without dynamics, periodic external current with slow frequency $$\varepsilon $$ ε lead to burst-like dynamics. patterns be understood using singular perturbation theory, specifically slow–fast dissection. With timescale separation leads variety phenomena their role for becomes inordinately more intricate. Canards are crucial understand route bursting. They describe trajectories evolving nearby repelling locally invariant sets system exist at transition between subthreshold Near = 0$$ xmlns:mml="http://www.w3.org/1998/Math/MathML">ε=0 , we peculiar jump-on canards which block continuous In biologically plausible -regime, this bursts emerge via consecutive spike-adding transitions. onset complex involves mixed-type-like torus form very first spikes burst follow fast-subsystem cycles. numerically evidence same mechanisms responsible QIF network plastic synapses. main conclusions apply network, owing exactness limit.

Язык: Английский

---

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex

The Journal of Physiology, Год журнала: 2024, Номер 602(5), С. 809 - 834

Опубликована: Фев. 14, 2024

Abstract Breathing behaviour involves the generation of normal breaths (eupnoea) on a timescale seconds and sigh order minutes. Both rhythms emerge in tandem from single brainstem site, but whether how cell population can generate two disparate remains unclear. We posit that recurrent synaptic excitation concert with depression cellular refractoriness gives rise to eupnoea rhythm, whereas an intracellular calcium oscillation is slower by orders magnitude rhythm. A mathematical model capturing these dynamics simultaneously generates frequencies, which be separately regulated physiological parameters. experimentally validated key predictions regarding signalling. All vertebrate brains feature network oscillator drives breathing pump for regular respiration. However, air‐breathing mammals compliant lungs susceptible collapse, rhythmogenic may have refashioned ubiquitous signalling systems produce second rhythm (for sighs) prevents atelectasis without impeding eupnoea. image Key points simplified activity‐based preBötC inspiratory neuron population. Inspiration attributable canonical excitatory mechanism. Sigh emerges The predicts perturbations uptake release across endoplasmic reticulum counterintuitively accelerate decelerate rhythmicity, respectively, was validated. Vertebrate evolution adapted existing mechanisms slow oscillations needed optimize pulmonary function mammals.

Язык: Английский

---

Amplitude-modulated spiking as a novel route to bursting: Coupling-induced mixed-mode oscillations by symmetry breaking

Chaos An Interdisciplinary Journal of Nonlinear Science, Год журнала: 2022, Номер 32(1)

Опубликована: Янв. 1, 2022

Mixed-mode oscillations consisting of alternating small- and large-amplitude are increasingly well understood often caused by folded singularities, canard orbits, or singular Hopf bifurcations. We show that coupling between identical nonlinear oscillators can cause mixed-mode because symmetry breaking. This behavior is illustrated for diffusively coupled FitzHugh-Nagumo with negative constant, we it a bifurcation related to saddle-node (FSN) singularity. Inspired earlier work on models pancreatic beta-cells [Sherman, Bull. Math. Biol. 56, 811 (1994)], then identify new type bursting dynamics due diffusive cells firing action potentials when isolated. In the presence coupling, small-amplitude in potential height precede transitions square-wave bursting. Confirming hypothesis from this pitchfork-of-limit-cycles fast subsystem, find Moreover, organized FSN averaged system, which causes bifurcation. Such recently studied so-called torus canards.

Язык: Английский

---

Carotid Bodies and the Integrated Cardiorespiratory Response to Hypoxia

Physiology, Год журнала: 2018, Номер 33(4), С. 281 - 297

Опубликована: Июнь 14, 2018

Advances in our understanding of brain mechanisms for the hypoxic ventilatory response, coordinated changes blood pressure, and long-term consequences chronic intermittent hypoxia as sleep apnea, such hypertension heart failure, are giving impetus to search therapies "erase" dysfunctional memories distributed carotid bodies central nervous system. We review current network models, open questions, sex differences, implications translational research.

Язык: Английский

---

Kinetic properties of persistent Na+ current orchestrate oscillatory bursting in respiratory neurons

The Journal of General Physiology, Год журнала: 2018, Номер 150(11), С. 1523 - 1540

Опубликована: Окт. 9, 2018

The rhythmic pattern of breathing depends on the pre-Bötzinger complex (preBötC) in brainstem, a vital circuit that contains population neurons with intrinsic oscillatory bursting behavior. Here, we investigate specific kinetic properties enable voltage-gated sodium channels to establish preBötC inspiratory neurons, which exhibit an unusually large persistent Na+ current (INaP). We first characterize kinetics INaP neonatal rat brainstem slices vitro, using whole-cell patch-clamp and computational modeling, then test contribution live dynamic clamp technique. provide evidence subthreshold activation, persistence at suprathreshold potentials, slow inactivation, recovery from inactivation are features regulate all aspects neurons. cumulative during burst active phase controls duration termination, while interburst interval. To demonstrate this mechanism, develop Markov state model explains comprehensive set voltage data. By adding or subtracting computer-generated neuron via clamp, able convert nonbursters into bursters, vice versa. As control, removed. Adding noninactivating results random transitions between sustained firing quiescence. relative amplitude is key factor separates bursters can change fraction preBötC. could thus be important target for regulating network rhythmogenic properties.

Язык: Английский

---

Putting the theory into ‘burstlet theory’ with a biophysical model of burstlets and bursts in the respiratory preBötzinger complex

eLife, Год журнала: 2022, Номер 11

Опубликована: Апрель 5, 2022

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBötzinger complex (preBötC). In vitro slice preparations containing preBötC, extracellular potassium must be elevated above physiological levels (to 7–9 mM) to observe regular rhythmic respiratory motor output hypoglossal nerve which preBötC projects. Reexamination of how K + affects has revealed that low-amplitude oscillations persist at levels. These oscillatory events are subthreshold standpoint transmission and dubbed burstlets. Burstlets neural rhythmogenic subpopulation within some instances may fail recruit larger network events, or bursts, required generate output. The fraction (burstlet fraction) decreases sigmoidally with increasing potassium. observations underlie burstlet theory rhythm generation. Experimental computational studies have suggested recruitment non-rhythmogenic component population requires intracellular Ca 2+ dynamics activation calcium-activated nonselective cationic current. this study, we show calcium driven by synaptically triggered influx well release/uptake endoplasmic reticulum conjunction current can reproduce offer an explanation for many key properties associated Altogether, our modeling work provides mechanistic basis unify wide range experimental findings on generation preBötC.

Язык: Английский

---