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Article ; Online: Emergent Elements of Inspiratory Rhythmogenesis: Network Synchronization and Synchrony Propagation.

Ashhad, Sufyan / Feldman, Jack L

2020 Volume 106, Issue 3, Page(s) 482–497.e4

Abstract: We assessed the mechanism of mammalian breathing rhythmogenesis in the preBötzinger complex (preBötC) in vitro, where experimental tests remain inconsistent with hypotheses of canonical rhythmogenic cellular or synaptic mechanisms, i.e., pacemaker ... ...

Abstract	We assessed the mechanism of mammalian breathing rhythmogenesis in the preBötzinger complex (preBötC) in vitro, where experimental tests remain inconsistent with hypotheses of canonical rhythmogenic cellular or synaptic mechanisms, i.e., pacemaker neurons or inhibition. Under rhythmic conditions, in each cycle, an inspiratory burst emerges as (presumptive) preBötC rhythmogenic neurons transition from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration (for ∼50-500 ms), which can trigger inspiratory bursts that propagate to motoneurons. In nonrhythmic conditions, antagonizing GABA
MeSH term(s)	Action Potentials ; Animals ; Central Pattern Generators/physiology ; Mice ; Models, Neurological ; Motor Neurons/metabolism ; Motor Neurons/physiology ; Receptors, GABA-A/metabolism ; Respiration ; Respiratory Center/physiology ; Synaptic Potentials
Chemical Substances	Receptors, GABA-A
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2020.02.005
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article: Precision Medicine for Breath-Focused Mind-Body Therapies for Stress and Anxiety: Are We Ready Yet?

Lavretsky, Helen / Feldman PhD, Jack L

Global advances in health and medicine

2021 Volume 10, Page(s) 2164956120986129

Abstract: In this viewpoint, we present an argument for transdisciplinary "precision medicine" approaches that combine studies of basic neurobiology of breathing in animal and human models of stress that can help characterize physiological and neural biomarkers ... ...

Abstract	In this viewpoint, we present an argument for transdisciplinary "precision medicine" approaches that combine studies of basic neurobiology of breathing in animal and human models of stress that can help characterize physiological and neural biomarkers and mechanisms of breathing control and emotion regulation in humans. Such mechanistic research is fundamental for the development of more effective and mechanism-based mind-body therapies. The potential for this research to positively impact public health is high, as breathing techniques are inexpensive, accessible, and cross-culturally accepted, with fewer complications then observed with other standard therapies for stress-related disorders.
Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2709002-4
ISSN	2164-9561 ; 2164-957X
ISSN (online)	2164-9561
ISSN	2164-957X
DOI	10.1177/2164956120986129
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Article ; Online: Breathing Rhythm and Pattern and Their Influence on Emotion.

Ashhad, Sufyan / Kam, Kaiwen / Del Negro, Christopher A / Feldman, Jack L

Annual review of neuroscience

2022 Volume 45, Page(s) 223–247

Abstract: Breathing is a vital rhythmic motor behavior with a surprisingly broad influence on the brain and body. The apparent simplicity of breathing belies a complex neural control system, the breathing central pattern generator (bCPG), that exhibits diverse ... ...

Abstract	Breathing is a vital rhythmic motor behavior with a surprisingly broad influence on the brain and body. The apparent simplicity of breathing belies a complex neural control system, the breathing central pattern generator (bCPG), that exhibits diverse operational modes to regulate gas exchange and coordinate breathing with an array of behaviors. In this review, we focus on selected advances in our understanding of the bCPG. At the core of the bCPG is the preBötzinger complex (preBötC), which drives inspiratory rhythm via an unexpectedly sophisticated emergent mechanism. Synchronization dynamics underlying preBötC rhythmogenesis imbue the system with robustness and lability. These dynamics are modulated by inputs from throughout the brain and generate rhythmic, patterned activity that is widely distributed. The connectivity and an emerging literature support a link between breathing, emotion, and cognition that is becoming experimentally tractable. These advances bring great potential for elucidating function and dysfunction in breathing and other mammalian neural circuits.
MeSH term(s)	Animals ; Brain ; Emotions ; Mammals ; Respiration ; Respiratory Center/physiology
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	282459-0
ISSN	1545-4126 ; 0147-006X
ISSN (online)	1545-4126
ISSN	0147-006X
DOI	10.1146/annurev-neuro-090121-014424
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Zs.A 1433: Show issues

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Article ; Online: Microcircuit Synchronization and Heavy-Tailed Synaptic Weight Distribution Augment preBötzinger Complex Bursting Dynamics.

Ashhad, Sufyan / Slepukhin, Valentin M / Feldman, Jack L / Levine, Alex J

The Journal of neuroscience : the official journal of the Society for Neuroscience

2022 Volume 43, Issue 2, Page(s) 240–260

Abstract: The preBötzinger Complex (preBötC) encodes inspiratory time as rhythmic bursts of activity underlying each breath. Spike synchronization throughout a sparsely connected preBötC microcircuit initiates bursts that ultimately drive the inspiratory motor ... ...

Abstract	The preBötzinger Complex (preBötC) encodes inspiratory time as rhythmic bursts of activity underlying each breath. Spike synchronization throughout a sparsely connected preBötC microcircuit initiates bursts that ultimately drive the inspiratory motor patterns. Using minimal microcircuit models to explore burst initiation dynamics, we examined the variability in probability and latency to burst following exogenous stimulation of a small subset of neurons, mimicking experiments. Among various physiologically plausible graphs of 1000 excitatory neurons constructed using experimentally determined synaptic and connectivity parameters, directed Erdős-Rényi graphs with a broad (lognormal) distribution of synaptic weights best captured the experimentally observed dynamics. preBötC synchronization leading to bursts was regulated by the efferent connectivity of spiking neurons that are optimally tuned to amplify modest preinspiratory activity through input convergence. Using graph-theoretic and machine learning-based analyses, we found that input convergence of efferent connectivity at the next-nearest neighbor order was a strong predictor of incipient synchronization. Our analyses revealed a crucial role of synaptic heterogeneity in imparting exceptionally robust yet flexible preBötC attractor dynamics. Given the pervasiveness of lognormally distributed synaptic strengths throughout the nervous system, we postulate that these mechanisms represent a ubiquitous template for temporal processing and decision-making computational motifs.
MeSH term(s)	Animals ; Respiratory Center/physiology ; Reproducibility of Results ; Neurons/physiology ; Respiration ; Mammals
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1195-22.2022
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Zs.A 1668: Show issues

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Article ; Online: Phase- and state-dependent modulation of breathing pattern by preBötzinger complex somatostatin expressing neurons.

de Sousa Abreu, Raquel P / Bondarenko, Evgeny / Feldman, Jack L

The Journal of physiology

2021 Volume 600, Issue 1, Page(s) 143–165

Abstract: As neuronal subtypes are increasingly categorized, delineating their functional role is paramount. The preBötzinger complex (preBötC) subpopulation expressing the neuropeptide somatostatin (SST) is classified as mostly excitatory, inspiratory-modulated ... ...

Abstract	As neuronal subtypes are increasingly categorized, delineating their functional role is paramount. The preBötzinger complex (preBötC) subpopulation expressing the neuropeptide somatostatin (SST) is classified as mostly excitatory, inspiratory-modulated and not rhythmogenic. We further characterized their phenotypic identity: 87% were glutamatergic and the balance were glycinergic and/or GABAergic. We then used optogenetics to investigate their modulatory role in both anaesthetized and freely moving mice. In anaesthetized mice, short photostimulation (100 ms) of preBötC SST
MeSH term(s)	Animals ; Channelrhodopsins ; Mice ; Neurons/metabolism ; Optogenetics ; Respiration ; Respiratory Center/metabolism ; Somatostatin/metabolism
Chemical Substances	Channelrhodopsins ; Somatostatin (51110-01-1)
Language	English
Publishing date	2021-12-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP282002
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Uc I Zs.65: Show issues

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Article ; Online: Octreotide's role in the management of post-esophagectomy chylothorax.

Deboever, Nathaniel / Feldman, Hope / Eisenberg, Michael / Antonoff, Mara B / Mehran, Reza J / Rajaram, Ravi / Rice, David C / Roth, Jack A / Sepesi, Boris / Swisher, Stephen G / Vaporciyan, Ara A / Walsh, Garrett L / Hofstetter, Wayne L

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

2024

Abstract: The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support ... ...

Abstract	The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doae011
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Zs.A 2378: Show issues

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Article ; Online: Efferent projections of excitatory and inhibitory preBötzinger Complex neurons.

Yang, Cindy F / Feldman, Jack L

The Journal of comparative neurology

2018 Volume 526, Issue 8, Page(s) 1389–1402

Abstract: The preBötzinger Complex (preBötC), a compact medullary region essential for generating normal breathing rhythm and pattern, is the kernel of the breathing central pattern generator (CPG). Excitatory preBötC neurons in rats project to major breathing- ... ...

Abstract	The preBötzinger Complex (preBötC), a compact medullary region essential for generating normal breathing rhythm and pattern, is the kernel of the breathing central pattern generator (CPG). Excitatory preBötC neurons in rats project to major breathing-related brainstem regions. Here, we provide a brainstem connectivity map in mice for both excitatory and inhibitory preBötC neurons. Using a genetic strategy to label preBötC neurons, we confirmed extensive projections of preBötC excitatory neurons within the brainstem breathing CPG including the contralateral preBötC, Bötzinger Complex (BötC), ventral respiratory group, nucleus of the solitary tract, parahypoglossal nucleus, parafacial region (RTN/pFRG or alternatively, pF
MeSH term(s)	Animals ; Choline O-Acetyltransferase/metabolism ; Efferent Pathways/physiology ; Forkhead Transcription Factors/metabolism ; Glycine Plasma Membrane Transport Proteins/genetics ; Glycine Plasma Membrane Transport Proteins/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Male ; Mice ; Mice, Transgenic ; Neural Inhibition/physiology ; Neurons/physiology ; Phosphopyruvate Hydratase/metabolism ; Prosencephalon/cytology ; Prosencephalon/metabolism ; Repressor Proteins/metabolism ; Respiratory Center/cytology ; Somatostatin/genetics ; Somatostatin/metabolism ; Transduction, Genetic
Chemical Substances	Forkhead Transcription Factors ; Foxp2 protein, mouse ; Glycine Plasma Membrane Transport Proteins ; Repressor Proteins ; Slc6a5 protein, mouse ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; Somatostatin (51110-01-1) ; Choline O-Acetyltransferase (EC 2.3.1.6) ; Phosphopyruvate Hydratase (EC 4.2.1.11)
Language	English
Publishing date	2018-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.24415
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Article ; Online: Precision Medicine for Breath-Focused Mind-Body Therapies for Stress and Anxiety

Helen Lavretsky MD, MS / Jack L Feldman PhD

Global Advances in Health and Medicine, Vol

Are We Ready Yet?

2021 Volume 10

Abstract: In this viewpoint, we present an argument for transdisciplinary “precision medicine” approaches that combine studies of basic neurobiology of breathing in animal and human models of stress that can help characterize physiological and neural biomarkers ... ...

Abstract	In this viewpoint, we present an argument for transdisciplinary “precision medicine” approaches that combine studies of basic neurobiology of breathing in animal and human models of stress that can help characterize physiological and neural biomarkers and mechanisms of breathing control and emotion regulation in humans. Such mechanistic research is fundamental for the development of more effective and mechanism-based mind-body therapies. The potential for this research to positively impact public health is high, as breathing techniques are inexpensive, accessible, and cross-culturally accepted, with fewer complications then observed with other standard therapies for stress-related disorders.
Keywords	Medicine (General) ; R5-920 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
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Article ; Online: Association between brain health outcomes and metabolic risk factors in persons with diabetes.

Reynolds, Evan L / Votruba, Kristen / Jack, Clifford R / Beare, Richard / Reid, Robert I / Preboske, Gregory M / Waseta, Camille / Pop-Busui, Rodica / Nelson, Robert G / Callaghan, Brian C / Feldman, Eva L

Annals of clinical and translational neurology

2023 Volume 10, Issue 10, Page(s) 1891–1898

Abstract: We performed a cross-sectional study to determine associations between cognition and MRI-derived brain outcomes, with obesity, diabetes duration, and metabolic risk factors in 51 Pima American Indians with longstanding type 2 diabetes (T2d) (mean [SD] ... ...

Abstract	We performed a cross-sectional study to determine associations between cognition and MRI-derived brain outcomes, with obesity, diabetes duration, and metabolic risk factors in 51 Pima American Indians with longstanding type 2 diabetes (T2d) (mean [SD] age: 48.4 [11.3] years, T2d duration: 20.1 [9.1] years). Participants had similar cognition (NIH Toolbox Cognition Battery composite: 45.3 [9.8], p = 0.64, n = 51) compared to normative data. T2d duration, but not other metabolic risk factors, associated with decreased cortical thickness (Point Estimate (PE): -0.0061, 95%CI: -0.0113, -0.0009, n = 45), gray matter volume (PE: -830.39, 95%CI: -1503.14, -157.64, n = 45), and increased white matter hyperintensity volume (PE: 0.0389, 95%CI: 0.0049, 0.0729, n = 45).
MeSH term(s)	Humans ; United States ; Middle Aged ; Diabetes Mellitus, Type 2/complications ; Brain/diagnostic imaging ; Brain/metabolism ; Cross-Sectional Studies ; Risk Factors ; Outcome Assessment, Health Care
Language	English
Publishing date	2023-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51859
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Article: Monosynaptic Projections to Excitatory and Inhibitory preBötzinger Complex Neurons.

Yang, Cindy F / Kim, Euiseok J / Callaway, Edward M / Feldman, Jack L

Frontiers in neuroanatomy

2020 Volume 14, Page(s) 58

Abstract: The key driver of breathing rhythm is the preBötzinger Complex (preBötC) whose activity is modulated by various functional inputs, e.g., volitional, physiological, and emotional. While the preBötC is highly interconnected with other regions of the ... ...

Abstract	The key driver of breathing rhythm is the preBötzinger Complex (preBötC) whose activity is modulated by various functional inputs, e.g., volitional, physiological, and emotional. While the preBötC is highly interconnected with other regions of the breathing central pattern generator (bCPG) in the brainstem, there is no data about the direct projections to either excitatory and inhibitory preBötC subpopulations from other elements of the bCPG or from suprapontine regions. Using modified rabies tracing, we identified neurons throughout the brain that send monosynaptic projections to identified excitatory and inhibitory preBötC neurons in mice. Within the brainstem, neurons from sites in the bCPG, including the contralateral preBötC, Bötzinger Complex, the nucleus of the solitary tract (NTS), parafacial region (pF
Language	English
Publishing date	2020-09-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2020.00058
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