Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat
Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that ge...
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description | Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.
Interactions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may func |
doi_str_mv | 10.1523/JNEUROSCI.0502-19.2019 |
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Interactions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may function as a premotor relay that integrates activity generated by diverse respiratory and nonrespiratory CPGs.</description><identifier>ISSN: 0270-6474</identifier><identifier>ISSN: 1529-2401</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.0502-19.2019</identifier><identifier>PMID: 31666354</identifier><language>eng</language><publisher>United States: Society for Neuroscience</publisher><subject>Animals ; Apnea ; Apnea - physiopathology ; Autonomic nervous system ; Central pattern generator ; Central Pattern Generators - physiology ; Choline O-Acetyltransferase - physiology ; Cholinergics ; Deglutition - physiology ; Female ; Glutamatergic transmission ; Hypercapnia - physiopathology ; Hypoxemia ; Hypoxia - physiopathology ; Larynx - physiology ; Male ; Mice ; Muscles ; Nerve Net - physiology ; Nerves ; Neurons ; Neurons - physiology ; Rats ; Respiration ; Respiratory Mechanics - physiology ; Reticular Formation - physiology ; Rhythms ; Swallowing ; Sympathetic nerves ; Sympathetic Nervous System - physiology ; Vagus nerve ; Vagus Nerve - physiology</subject><ispartof>The Journal of neuroscience, 2019-12, Vol.39 (49), p.9757-9766</ispartof><rights>Copyright © 2019 the authors.</rights><rights>Copyright Society for Neuroscience Dec 4, 2019</rights><rights>Copyright © 2019 the authors 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c561t-be1c6dfa6b975c1466e5cbbe7725aef106ee88312f55dc20e1f160f7d6c8c4663</citedby><cites>FETCH-LOGICAL-c561t-be1c6dfa6b975c1466e5cbbe7725aef106ee88312f55dc20e1f160f7d6c8c4663</cites><orcidid>0000-0002-4917-7734 ; 0000-0001-6468-8922 ; 0000-0001-8517-1738 ; 0000-0003-3624-9839 ; 0000-0003-4712-8792 ; 0000-0002-9854-1029</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891060/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891060/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31666354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toor, Rahat Ul Ain Summan</creatorcontrib><creatorcontrib>Sun, Qi-Jian</creatorcontrib><creatorcontrib>Kumar, Natasha N</creatorcontrib><creatorcontrib>Le, Sheng</creatorcontrib><creatorcontrib>Hildreth, Cara M</creatorcontrib><creatorcontrib>Phillips, Jacqueline K</creatorcontrib><creatorcontrib>McMullan, Simon</creatorcontrib><title>Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.
Interactions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may function as a premotor relay that integrates activity generated by diverse respiratory and nonrespiratory CPGs.</description><subject>Animals</subject><subject>Apnea</subject><subject>Apnea - physiopathology</subject><subject>Autonomic nervous system</subject><subject>Central pattern generator</subject><subject>Central Pattern Generators - physiology</subject><subject>Choline O-Acetyltransferase - physiology</subject><subject>Cholinergics</subject><subject>Deglutition - physiology</subject><subject>Female</subject><subject>Glutamatergic transmission</subject><subject>Hypercapnia - physiopathology</subject><subject>Hypoxemia</subject><subject>Hypoxia - physiopathology</subject><subject>Larynx - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Muscles</subject><subject>Nerve Net - physiology</subject><subject>Nerves</subject><subject>Neurons</subject><subject>Neurons - physiology</subject><subject>Rats</subject><subject>Respiration</subject><subject>Respiratory Mechanics - physiology</subject><subject>Reticular Formation - physiology</subject><subject>Rhythms</subject><subject>Swallowing</subject><subject>Sympathetic nerves</subject><subject>Sympathetic Nervous System - physiology</subject><subject>Vagus nerve</subject><subject>Vagus Nerve - physiology</subject><issn>0270-6474</issn><issn>1529-2401</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkcFO3DAQhq2qVVloXwFF6qUHsvU4aye5VEIraLdCS7VbzpbjTMAoa6e2A9qX6DPjCFi1Pfnwf_ONRz8hp0DnwFnx5cf64mZzvV2u5pRTlkM9ZxTqN2SW0jpnCwpvyYyykuZiUS6OyHEI95TSkkL5nhwVIIQo-GJG_qxx9M6GzNgs3mG2shH9DlujImYbjEaPvfLZetQ9jiFbOudbY6fwpwvR2DAYr6Lz--xcR_Ng4v4s2z6qvnePxt6eZcq2SXOg8u1-N6i0KImTbBz6RL3u3qj4gbzrVB_w48t7Qm4uL34tv-dX199Wy_OrXHMBMW8QtGg7JZq65BoWQiDXTYNlybjCDqhArKoCWMd5qxlF6EDQrmyFrnSiixPy9dk7jE26VqONXvVy8Gan_F46ZeS_iTV38tY9SFHVyU6T4POLwLvfI4YodyZo7Htl0Y1BsgJoCRwqSOin_9B7N3qbzksUqwpaVDBR4pnS3oXgsTt8BqicKpeHyuVUuYRaTpWnwdO_TzmMvXZcPAFYSqzO</recordid><startdate>20191204</startdate><enddate>20191204</enddate><creator>Toor, Rahat Ul Ain Summan</creator><creator>Sun, Qi-Jian</creator><creator>Kumar, Natasha N</creator><creator>Le, Sheng</creator><creator>Hildreth, Cara M</creator><creator>Phillips, Jacqueline K</creator><creator>McMullan, Simon</creator><general>Society for Neuroscience</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4917-7734</orcidid><orcidid>https://orcid.org/0000-0001-6468-8922</orcidid><orcidid>https://orcid.org/0000-0001-8517-1738</orcidid><orcidid>https://orcid.org/0000-0003-3624-9839</orcidid><orcidid>https://orcid.org/0000-0003-4712-8792</orcidid><orcidid>https://orcid.org/0000-0002-9854-1029</orcidid></search><sort><creationdate>20191204</creationdate><title>Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat</title><author>Toor, Rahat Ul Ain Summan ; Sun, Qi-Jian ; Kumar, Natasha N ; Le, Sheng ; Hildreth, Cara M ; Phillips, Jacqueline K ; McMullan, Simon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c561t-be1c6dfa6b975c1466e5cbbe7725aef106ee88312f55dc20e1f160f7d6c8c4663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Apnea</topic><topic>Apnea - physiopathology</topic><topic>Autonomic nervous system</topic><topic>Central pattern generator</topic><topic>Central Pattern Generators - physiology</topic><topic>Choline O-Acetyltransferase - physiology</topic><topic>Cholinergics</topic><topic>Deglutition - physiology</topic><topic>Female</topic><topic>Glutamatergic transmission</topic><topic>Hypercapnia - physiopathology</topic><topic>Hypoxemia</topic><topic>Hypoxia - physiopathology</topic><topic>Larynx - physiology</topic><topic>Male</topic><topic>Mice</topic><topic>Muscles</topic><topic>Nerve Net - physiology</topic><topic>Nerves</topic><topic>Neurons</topic><topic>Neurons - physiology</topic><topic>Rats</topic><topic>Respiration</topic><topic>Respiratory Mechanics - physiology</topic><topic>Reticular Formation - physiology</topic><topic>Rhythms</topic><topic>Swallowing</topic><topic>Sympathetic nerves</topic><topic>Sympathetic Nervous System - physiology</topic><topic>Vagus nerve</topic><topic>Vagus Nerve - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toor, Rahat Ul Ain Summan</creatorcontrib><creatorcontrib>Sun, Qi-Jian</creatorcontrib><creatorcontrib>Kumar, Natasha N</creatorcontrib><creatorcontrib>Le, Sheng</creatorcontrib><creatorcontrib>Hildreth, Cara M</creatorcontrib><creatorcontrib>Phillips, Jacqueline K</creatorcontrib><creatorcontrib>McMullan, Simon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toor, Rahat Ul Ain Summan</au><au>Sun, Qi-Jian</au><au>Kumar, Natasha N</au><au>Le, Sheng</au><au>Hildreth, Cara M</au><au>Phillips, Jacqueline K</au><au>McMullan, Simon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2019-12-04</date><risdate>2019</risdate><volume>39</volume><issue>49</issue><spage>9757</spage><epage>9766</epage><pages>9757-9766</pages><issn>0270-6474</issn><issn>1529-2401</issn><eissn>1529-2401</eissn><abstract>Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.
Interactions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may function as a premotor relay that integrates activity generated by diverse respiratory and nonrespiratory CPGs.</abstract><cop>United States</cop><pub>Society for Neuroscience</pub><pmid>31666354</pmid><doi>10.1523/JNEUROSCI.0502-19.2019</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4917-7734</orcidid><orcidid>https://orcid.org/0000-0001-6468-8922</orcidid><orcidid>https://orcid.org/0000-0001-8517-1738</orcidid><orcidid>https://orcid.org/0000-0003-3624-9839</orcidid><orcidid>https://orcid.org/0000-0003-4712-8792</orcidid><orcidid>https://orcid.org/0000-0002-9854-1029</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Apnea Apnea - physiopathology Autonomic nervous system Central pattern generator Central Pattern Generators - physiology Choline O-Acetyltransferase - physiology Cholinergics Deglutition - physiology Female Glutamatergic transmission Hypercapnia - physiopathology Hypoxemia Hypoxia - physiopathology Larynx - physiology Male Mice Muscles Nerve Net - physiology Nerves Neurons Neurons - physiology Rats Respiration Respiratory Mechanics - physiology Reticular Formation - physiology Rhythms Swallowing Sympathetic nerves Sympathetic Nervous System - physiology Vagus nerve Vagus Nerve - physiology |
title | Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat |
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