Opioid Sensitivity Reveals Two Distinct Rhythmogenic States of the Respiratory Network

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan–anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and “limit” changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.

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The UK’s Global Health Respiratory Network: Improving respiratory health of the world's poorest through research collaborations

Journal of Global Health ◽

10.7189/jogh.09.020104 ◽

2019 ◽

Vol 9 (2) ◽

Cited By ~ 1

Author(s):

Aziz Sheikh ◽

Harry Campbell ◽

Dominique Balharry ◽

Peymané Adab ◽

Mauricio L Barreto3 ◽

...

Keyword(s):

Global Health ◽

Respiratory Health ◽

Research Collaborations ◽

Respiratory Network

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Reciprocal connectivity of the periaqueductal gray with the ponto-medullary respiratory network in rat

10.1101/2020.09.15.298927 ◽

2020 ◽

Author(s):

Pedro Trevizan-Baú ◽

Werner I. Furuya ◽

Stuart B. Mazzone ◽

Davor Stanić ◽

Rishi R. Dhingra ◽

...

Keyword(s):

Respiratory Rhythm ◽

Upper Airway ◽

Periaqueductal Gray ◽

List Type ◽

Airway Patency ◽

Respiratory Network ◽

Cholera Toxin Subunit B ◽

Motor Activities ◽

Descending Projections ◽

Subunit B

AbstractSynaptic activities of the periaqueductal gray (PAG) can modulate or appropriate the respiratory motor activities in the context of behavior and emotion via descending projections to nucleus retroambiguus. However, alternative anatomical pathways for the mediation of PAG-evoked respiratory modulation via core nuclei of the brainstem respiratory network remains only partially described. We injected the retrograde tracer Cholera toxin subunit B (CT-B) in the pontine Kölliker-Fuse nucleus (KFn, n=5), medullary Bötzinger (BötC, n=3) and pre-Bötzinger complexes (pre-BötC; n=3), and the caudal raphé nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BötC, and caudal raphé, but not in the BötC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections into the lateral and ventrolateral PAG columns (n=4) yield the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BötC and caudal raphé. Analysis of the relative projection strength revealed that the KFn shares the densest reciprocal connectivity with the PAG (ventrolateral and lateral columns, in particular). Overall, our data imply that the PAG may engage a distributed respiratory rhythm and pattern generating network beyond the nucleus retroambiguus to mediate downstream modulation of breathing. However, the reciprocal connectivity of the KFn and PAG suggests specific roles for synaptic interaction between these two nuclei that are most likely related to the regulation of upper airway patency during vocalization or other volitional orofacial behaviors.HighlightsThe lateral and ventrolateral PAG project to the primary respiratory network.The Kölliker-Fuse nucleus shares the densest reciprocal connectivity with the PAG.The Bötzinger complex appears to have very little connectivity with the PAG.

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Modulation and reconfiguration of the pontomedullary respiratory network: A computational modeling study

The FASEB Journal ◽

10.1096/fasebj.21.5.a559-a ◽

2007 ◽

Vol 21 (5) ◽

Cited By ~ 1

Author(s):

B G Lindsey ◽

A Ross ◽

R O'Connor ◽

K F Morris ◽

S C Nuding ◽

...

Keyword(s):

Computational Modeling ◽

Respiratory Network ◽

Modeling Study

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Sex in the brain: hormones and sex differences

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2016.18.4/jmarrocco ◽

2016 ◽

Vol 18 (4) ◽

pp. 373-383 ◽

Cited By ~ 45

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Genetic Factors ◽

Motor Coordination ◽

Brain Regions ◽

New Era ◽

Brain Functions ◽

Opioid Sensitivity ◽

Males And Females ◽

The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

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