Inhibitory Subpopulations in preBötzinger Complex Play Distinct Roles in Modulating Inspiratory Rhythm and Pattern

Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2 ) and glycinergic (GlyT2 ) neurons are functionally and an...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of neuroscience Vol. 44; no. 25; p. 1
Main Authors Chang, Zheng, Skach, Jordan, Kam, Kaiwen
Format Journal Article
LanguageEnglish
Published United States Society for Neuroscience 19.06.2024
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2 ) and glycinergic (GlyT2 ) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1 ) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2 , GAD1 , or GAD2 neurons. We found that the majority of preBötC inhibitory neurons expressed both GlyT2 and GAD2 while a much smaller subpopulation also expressed GAD1. To determine the functional role of these subpopulations, we used holographic photostimulation, a patterned illumination technique, in rhythmically active medullary slices from neonatal Dbx1 ;GlyT2 and Dbx1 ;GAD1 double reporter mice of either sex. Stimulation of 4 or 8 preBötC GlyT2 neurons during endogenous rhythm prolonged the interburst interval in a phase-dependent manner and increased the latency to burst initiation when bursts were evoked by stimulation of Dbx1 neurons. In contrast, stimulation of 4 or 8 preBötC GAD1 neurons did not affect interburst interval or latency to burst initiation. Instead, photoactivation of GAD1 neurons during the inspiratory burst prolonged endogenous and evoked burst duration and decreased evoked burst amplitude. We conclude that GlyT2 /GAD2 neurons modulate breathing rhythm by delaying burst initiation while a smaller GAD1 subpopulation shapes inspiratory patterning by altering burst duration and amplitude.
AbstractList Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2 ) and glycinergic (GlyT2 ) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1 ) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2 , GAD1 , or GAD2 neurons. We found that the majority of preBötC inhibitory neurons expressed both GlyT2 and GAD2 while a much smaller subpopulation also expressed GAD1. To determine the functional role of these subpopulations, we used holographic photostimulation, a patterned illumination technique, in rhythmically active medullary slices from neonatal Dbx1 ;GlyT2 and Dbx1 ;GAD1 double reporter mice of either sex. Stimulation of 4 or 8 preBötC GlyT2 neurons during endogenous rhythm prolonged the interburst interval in a phase-dependent manner and increased the latency to burst initiation when bursts were evoked by stimulation of Dbx1 neurons. In contrast, stimulation of 4 or 8 preBötC GAD1 neurons did not affect interburst interval or latency to burst initiation. Instead, photoactivation of GAD1 neurons during the inspiratory burst prolonged endogenous and evoked burst duration and decreased evoked burst amplitude. We conclude that GlyT2 /GAD2 neurons modulate breathing rhythm by delaying burst initiation while a smaller GAD1 subpopulation shapes inspiratory patterning by altering burst duration and amplitude.
Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2+) and glycinergic (GlyT2+) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1+) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2+, GAD1+, or GAD2+ neurons. We found that the majority of preBötC inhibitory neurons expressed both GlyT2 and GAD2 while a much smaller subpopulation also expressed GAD1. To determine the functional role of these subpopulations, we used holographic photostimulation, a patterned illumination technique, in rhythmically active medullary slices from neonatal Dbx1tdTomato;GlyT2EGFP and Dbx1tdTomato;GAD1EGFP double reporter mice of either sex. Stimulation of 4 or 8 preBötC GlyT2+ neurons during endogenous rhythm prolonged the interburst interval in a phase-dependent manner and increased the latency to burst initiation when bursts were evoked by stimulation of Dbx1+ neurons. In contrast, stimulation of 4 or 8 preBötC GAD1+ neurons did not affect interburst interval or latency to burst initiation. Instead, photoactivation of GAD1+ neurons during the inspiratory burst prolonged endogenous and evoked burst duration and decreased evoked burst amplitude. We conclude that GlyT2+/GAD2+ neurons modulate breathing rhythm by delaying burst initiation while a smaller GAD1+ subpopulation shapes inspiratory patterning by altering burst duration and amplitude.Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2+) and glycinergic (GlyT2+) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1+) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2+, GAD1+, or GAD2+ neurons. We found that the majority of preBötC inhibitory neurons expressed both GlyT2 and GAD2 while a much smaller subpopulation also expressed GAD1. To determine the functional role of these subpopulations, we used holographic photostimulation, a patterned illumination technique, in rhythmically active medullary slices from neonatal Dbx1tdTomato;GlyT2EGFP and Dbx1tdTomato;GAD1EGFP double reporter mice of either sex. Stimulation of 4 or 8 preBötC GlyT2+ neurons during endogenous rhythm prolonged the interburst interval in a phase-dependent manner and increased the latency to burst initiation when bursts were evoked by stimulation of Dbx1+ neurons. In contrast, stimulation of 4 or 8 preBötC GAD1+ neurons did not affect interburst interval or latency to burst initiation. Instead, photoactivation of GAD1+ neurons during the inspiratory burst prolonged endogenous and evoked burst duration and decreased evoked burst amplitude. We conclude that GlyT2+/GAD2+ neurons modulate breathing rhythm by delaying burst initiation while a smaller GAD1+ subpopulation shapes inspiratory patterning by altering burst duration and amplitude.
Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2+) and glycinergic (GlyT2+) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1+) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2+, GAD1+, or GAD2+ neurons. We found that the majority of preBötC inhibitory neurons expressed both GlyT2 and GAD2 while a much smaller subpopulation also expressed GAD1. To determine the functional role of these subpopulations, we used holographic photostimulation, a patterned illumination technique, in rhythmically active medullary slices from neonatal Dbx1tdTomato;GlyT2EGFP and Dbx1tdTomato;GAD1EGFP double reporter mice of either sex. Stimulation of 4 or 8 preBötC GlyT2+ neurons during endogenous rhythm prolonged the interburst interval in a phase-dependent manner and increased the latency to burst initiation when bursts were evoked by stimulation of Dbx1+ neurons. In contrast, stimulation of 4 or 8 preBötC GAD1+ neurons did not affect interburst interval or latency to burst initiation. Instead, photoactivation of GAD1+ neurons during the inspiratory burst prolonged endogenous and evoked burst duration and decreased evoked burst amplitude. We conclude that GlyT2+/GAD2+ neurons modulate breathing rhythm by delaying burst initiation while a smaller GAD1+ subpopulation shapes inspiratory patterning by altering burst duration and amplitude.
Author Skach, Jordan
Chang, Zheng
Kam, Kaiwen
Author_xml – sequence: 1
  givenname: Zheng
  surname: Chang
  fullname: Chang, Zheng
  organization: Stanson Toshok Center for Brain Function and Repair, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064
– sequence: 2
  givenname: Jordan
  surname: Skach
  fullname: Skach, Jordan
  organization: Stanson Toshok Center for Brain Function and Repair, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064
– sequence: 3
  givenname: Kaiwen
  orcidid: 0000-0002-8479-0542
  surname: Kam
  fullname: Kam, Kaiwen
  email: kaiwen.kam@rosalindfranklin.edu
  organization: Stanson Toshok Center for Brain Function and Repair, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064 kaiwen.kam@rosalindfranklin.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/38729762$$D View this record in MEDLINE/PubMed
BookMark eNpd0M9uGjEQBnCrStUA6StElnLJZen4D-v1saE0oaIlIuGM7LUJjnbtje2VSh8sL5AXK6L0ktMc5vd9Gs0QnfngLUKXBMZkQtmXH79m69XyYTofE0mrgrIxBco_oMFhKwvKgZyhAVABRckFP0fDlJ4BQAARn9A5qwSVoqQDlOZ-57TLIe7xQ6-70PWNyi74hJ3HXbQ3b6_5j_NPNuJpaLvG_sb3jdrjby5l5-uMV6GxR_wzmGPWP-G5T52L6ti62u3zrsXKG3yvcrbRX6CPW9Uk-_k0R2j9ffY4vSsWy9v59Oui6Egpc0EnhitZa2klNbosLWFbZYGQitfCAqMa2LZWYBSvSGmsMcAIl8JoqLVmFRuh63-9XQwvvU1507pU26ZR3oY-bRhMmBRcVuWBXr2jz6GP_nDdQQnKoCJHdXlSvW6t2XTRtSruN__fyf4CAAV9Tw
ContentType Journal Article
Copyright Copyright © 2024 the authors.
Copyright Society for Neuroscience Jun 19, 2024
Copyright_xml – notice: Copyright © 2024 the authors.
– notice: Copyright Society for Neuroscience Jun 19, 2024
DBID CGR
CUY
CVF
ECM
EIF
NPM
7QG
7QR
7TK
7U7
7U9
8FD
C1K
FR3
H94
P64
7X8
DOI 10.1523/JNEUROSCI.1928-23.2024
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Animal Behavior Abstracts
Chemoreception Abstracts
Neurosciences Abstracts
Toxicology Abstracts
Virology and AIDS Abstracts
Technology Research Database
Environmental Sciences and Pollution Management
Engineering Research Database
AIDS and Cancer Research Abstracts
Biotechnology and BioEngineering Abstracts
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Virology and AIDS Abstracts
Technology Research Database
Toxicology Abstracts
Animal Behavior Abstracts
AIDS and Cancer Research Abstracts
Chemoreception Abstracts
Engineering Research Database
Neurosciences Abstracts
Biotechnology and BioEngineering Abstracts
Environmental Sciences and Pollution Management
MEDLINE - Academic
DatabaseTitleList MEDLINE
MEDLINE - Academic
Virology and AIDS Abstracts
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Anatomy & Physiology
EISSN 1529-2401
ExternalDocumentID 38729762
Genre Journal Article
GrantInformation_xml – fundername: NINDS NIH HHS
  grantid: R01 NS097492
GroupedDBID ---
-DZ
-~X
.55
18M
34G
39C
53G
5GY
5RE
AAFWJ
ABBAR
ABIVO
ACGUR
ACNCT
ADBBV
AENEX
AFCFT
AFHIN
AFOSN
AHWXS
AIZTS
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BTFSW
CGR
CS3
CUY
CVF
DIK
DU5
E3Z
EBS
ECM
EIF
EJD
F5P
GX1
H13
H~9
KQ8
L7B
NPM
OK1
P0W
P2P
QZG
R.V
RHF
RHI
RPM
TFN
TR2
WH7
WOQ
X7M
YBU
YHG
YKV
YNH
YSK
7QG
7QR
7TK
7U7
7U9
8FD
C1K
FR3
H94
P64
7X8
ID FETCH-LOGICAL-p169t-25d4a9cb9e92db66e13fae01184c7e032b03fca0da4816dedd031497db0cbb383
ISSN 0270-6474
1529-2401
IngestDate Sat Oct 26 04:50:51 EDT 2024
Thu Oct 10 22:03:03 EDT 2024
Sat Nov 02 12:27:59 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 25
Keywords inhibition
motor systems
breathing
central pattern generator
Language English
License Copyright © 2024 the authors.
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-p169t-25d4a9cb9e92db66e13fae01184c7e032b03fca0da4816dedd031497db0cbb383
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0002-8479-0542
PMID 38729762
PQID 3072308186
PQPubID 2049535
ParticipantIDs proquest_miscellaneous_3053974986
proquest_journals_3072308186
pubmed_primary_38729762
PublicationCentury 2000
PublicationDate 2024-Jun-19
20240619
PublicationDateYYYYMMDD 2024-06-19
PublicationDate_xml – month: 06
  year: 2024
  text: 2024-Jun-19
  day: 19
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: Baltimore
PublicationTitle The Journal of neuroscience
PublicationTitleAlternate J Neurosci
PublicationYear 2024
Publisher Society for Neuroscience
Publisher_xml – name: Society for Neuroscience
References 37609332 - bioRxiv. 2023 Sep 01:2023.08.07.552303. doi: 10.1101/2023.08.07.552303
References_xml
SSID ssj0007017
Score 2.5007703
Snippet Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 1
SubjectTerms Amplitudes
Animals
Animals, Newborn
Brain slice preparation
Dbx1 protein
Female
Glutamate Decarboxylase - genetics
Glutamate Decarboxylase - metabolism
Glutamatergic transmission
Glycine Plasma Membrane Transport Proteins - genetics
Glycine Plasma Membrane Transport Proteins - metabolism
Glycine transporter
Inhalation - physiology
Latency
Male
Medulla Oblongata - cytology
Medulla Oblongata - physiology
Mice
Mice, Transgenic
Neonates
Neural Inhibition - physiology
Neural networks
Neurogenesis
Neurons
Neurons - physiology
Patterning
Periodicity
Photoactivation
Respiration
Respiratory Center - cytology
Respiratory Center - physiology
Rhythm
Rhythms
Spatial distribution
Stimulation
Subpopulations
γ-Aminobutyric acid
Title Inhibitory Subpopulations in preBötzinger Complex Play Distinct Roles in Modulating Inspiratory Rhythm and Pattern
URI https://www.ncbi.nlm.nih.gov/pubmed/38729762
https://www.proquest.com/docview/3072308186
https://www.proquest.com/docview/3053974986
Volume 44
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1fSxwxEA-tQvFFWm2rrZUUxJdy193N_sujHoreoahVkL4cyW6WW9DcoSvt-cH6BfrFOpNk_4gKbV-WZZNsIPPL7GRn5jeEbEWFr1gi4h4DwMABBe54ESGNq_DyJJJpYjLkjo7jg4tweBldtnG6Jrukkv3s_sm8kv-RKjwDuWKW7D9ItnkpPIB7kC9cQcJw_SsZH-pJKUvjJgcFMGtqcdnY8Bu1i27w3bi6t2yDuPev1E8sVDRH2s2q1Fn15QwpnXDA0TQ3420IQeOAP5vMq4ktpHFiyDh116BtU8uMUduhx2wQM6j_SX-fKPedNFW_hK1CNYTjbwvRkQXoSJQ_XJKa-yURhBg65RSfcmo0MH4bv6tnLc-jw5PNdn6kvyPDIzE8xjDGb4PDPtifIHLWx1m6A0AOs2sjVZbC8aDW6A-Zs-uml2QRaRKxssLotOWST0AZuZxxmPbr05MukVf1a54_gxhb5Pw1WXbrTXcsIt6QF0qvkNUdDQK7ntNtasJ6jb9kldy2IKEPQUJLTREkv385gFAHEIoAoTVAqAEIdm4BQjsAoRYgFABCHUDekov9vfPBQc9V2ujN_JhXvSDKQ8EzyRUPchnHymeFUJiUHGaJ8lggPVZksHtFmPpxrvIcqx7wJJdeJiVL2TuyoKdarRHKAi6LIPNlkclQiSTlCfelVIEXqzAVbJ1s1Ks4dlvpdgwfGjgKI7niOvncNIOiQ--V0Gp6h30isJ1Djn3e29Ufzywjy7gW0YdnWz6SpRapG2ShurlTn8CcrOSmQcUfDWR5Aw
link.rule.ids 314,780,784,27924,27925
linkProvider Colorado Alliance of Research Libraries
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Inhibitory+Subpopulations+in+preB%C3%B6tzinger+Complex+Play+Distinct+Roles+in+Modulating+Inspiratory+Rhythm+and+Pattern&rft.jtitle=The+Journal+of+neuroscience&rft.au=Chang%2C+Zheng&rft.au=Skach%2C+Jordan&rft.au=Kam%2C+Kaiwen&rft.date=2024-06-19&rft.eissn=1529-2401&rft.volume=44&rft.issue=25&rft_id=info:doi/10.1523%2FJNEUROSCI.1928-23.2024&rft_id=info%3Apmid%2F38729762&rft.externalDocID=38729762
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0270-6474&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0270-6474&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0270-6474&client=summon