Activation of the periaqueductal gray controls respiratory output through a distributed brain network
IntroductionThe periaqueductal gray (PAG) has been previously established to play a key role in producing the vital changes in respiration occurring in response to threat. However, it is not fully understood how PAG activation alters the ongoing respiratory output, nor it is understood which pathway...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1516771/full |
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| author | Mitchell Prostebby Jashan Saini Vivian Biancardi Vivian Biancardi Vivian Biancardi Clayton T. Dickson Clayton T. Dickson Clayton T. Dickson Clayton T. Dickson Silvia Pagliardini Silvia Pagliardini Silvia Pagliardini |
| author_facet | Mitchell Prostebby Jashan Saini Vivian Biancardi Vivian Biancardi Vivian Biancardi Clayton T. Dickson Clayton T. Dickson Clayton T. Dickson Clayton T. Dickson Silvia Pagliardini Silvia Pagliardini Silvia Pagliardini |
| author_sort | Mitchell Prostebby |
| collection | DOAJ |
| description | IntroductionThe periaqueductal gray (PAG) has been previously established to play a key role in producing the vital changes in respiration occurring in response to threat. However, it is not fully understood how PAG activation alters the ongoing respiratory output, nor it is understood which pathways mediate these effects, as several regions have been previously identified to influence respiratory activity.MethodsWe used optogenetic tools in conjunction with EMG recordings of inspiratory and expiratory musculature to determine how PAG activation on short (250 ms) and longer (10–15 s) timescales alters respiratory muscle activity. Through cFOS mapping, we also identified key downstream brain regions which were likely modulated by PAG activation including the preBötzinger Complex (preBötC) and the lateral parafacial area (pFL). We then stimulated PAG terminals in those regions to determine whether their activity can account for the observed effects of PAG stimulation.ResultsDirectly stimulating the PAG resulted in prominent changes to all recorded muscle activities and reset the breathing rhythm in either a phase-independent or phase-dependent manner. In contrast, stimulating PAG terminals in either preBötC or pFL with long or shorter timescale stimuli could not completely replicate the effects of direct PAG stimulation and also did not produce any respiratory reset.ConclusionsOur results show that the effects of PAG activity on respiration are not mediated solely by PAG inputs to either the preBötC or pFL and more likely involve integration across a larger network of brainstem areas. |
| format | Article |
| id | doaj-art-da4f8acb9bf44d95b9ac9bee9f36e365 |
| institution | Kabale University |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-da4f8acb9bf44d95b9ac9bee9f36e3652025-01-22T07:11:29ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-01-011610.3389/fphys.2025.15167711516771Activation of the periaqueductal gray controls respiratory output through a distributed brain networkMitchell Prostebby0Jashan Saini1Vivian Biancardi2Vivian Biancardi3Vivian Biancardi4Clayton T. Dickson5Clayton T. Dickson6Clayton T. Dickson7Clayton T. Dickson8Silvia Pagliardini9Silvia Pagliardini10Silvia Pagliardini11Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaNeuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaWomen and Children’s Health Research Institute, University of Alberta, Edmonton, AB, CanadaNeuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaWomen and Children’s Health Research Institute, University of Alberta, Edmonton, AB, CanadaDepartment of Psychology, University of Alberta, Edmonton, AB, CanadaNeuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaWomen and Children’s Health Research Institute, University of Alberta, Edmonton, AB, CanadaIntroductionThe periaqueductal gray (PAG) has been previously established to play a key role in producing the vital changes in respiration occurring in response to threat. However, it is not fully understood how PAG activation alters the ongoing respiratory output, nor it is understood which pathways mediate these effects, as several regions have been previously identified to influence respiratory activity.MethodsWe used optogenetic tools in conjunction with EMG recordings of inspiratory and expiratory musculature to determine how PAG activation on short (250 ms) and longer (10–15 s) timescales alters respiratory muscle activity. Through cFOS mapping, we also identified key downstream brain regions which were likely modulated by PAG activation including the preBötzinger Complex (preBötC) and the lateral parafacial area (pFL). We then stimulated PAG terminals in those regions to determine whether their activity can account for the observed effects of PAG stimulation.ResultsDirectly stimulating the PAG resulted in prominent changes to all recorded muscle activities and reset the breathing rhythm in either a phase-independent or phase-dependent manner. In contrast, stimulating PAG terminals in either preBötC or pFL with long or shorter timescale stimuli could not completely replicate the effects of direct PAG stimulation and also did not produce any respiratory reset.ConclusionsOur results show that the effects of PAG activity on respiration are not mediated solely by PAG inputs to either the preBötC or pFL and more likely involve integration across a larger network of brainstem areas.https://www.frontiersin.org/articles/10.3389/fphys.2025.1516771/fullperiaqueductal grayoptogeneticsrespiratory controlrespiratory resetPreBotzinger complex |
| spellingShingle | Mitchell Prostebby Jashan Saini Vivian Biancardi Vivian Biancardi Vivian Biancardi Clayton T. Dickson Clayton T. Dickson Clayton T. Dickson Clayton T. Dickson Silvia Pagliardini Silvia Pagliardini Silvia Pagliardini Activation of the periaqueductal gray controls respiratory output through a distributed brain network Frontiers in Physiology periaqueductal gray optogenetics respiratory control respiratory reset PreBotzinger complex |
| title | Activation of the periaqueductal gray controls respiratory output through a distributed brain network |
| title_full | Activation of the periaqueductal gray controls respiratory output through a distributed brain network |
| title_fullStr | Activation of the periaqueductal gray controls respiratory output through a distributed brain network |
| title_full_unstemmed | Activation of the periaqueductal gray controls respiratory output through a distributed brain network |
| title_short | Activation of the periaqueductal gray controls respiratory output through a distributed brain network |
| title_sort | activation of the periaqueductal gray controls respiratory output through a distributed brain network |
| topic | periaqueductal gray optogenetics respiratory control respiratory reset PreBotzinger complex |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1516771/full |
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