Prostebby Mitchell, Saini Jashan, Biancardi Vivian, Dickson Clayton T, Pagliardini Silvia
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Department of Physiology, University of Alberta, Edmonton, AB, Canada.
Front Physiol. 2025 Jan 22;16:1516771. doi: 10.3389/fphys.2025.1516771. eCollection 2025.
The 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.
We 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.
Directly 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.
Our 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.
中脑导水管周围灰质（PAG）先前已被证实，在产生因威胁而出现的呼吸重要变化中起关键作用。然而，目前尚不完全清楚PAG激活如何改变正在进行的呼吸输出，也不清楚哪些通路介导这些效应，因为先前已确定有几个区域会影响呼吸活动。
我们使用光遗传学工具结合吸气和呼气肌肉组织的肌电图记录，以确定在短（250毫秒）和长（10 - 15秒）时间尺度上PAG激活如何改变呼吸肌肉活动。通过cFOS图谱，我们还确定了可能受PAG激活调节的关键下游脑区，包括前包钦格复合体（preBötC）和外侧面部旁区（pFL）。然后，我们刺激这些区域的PAG终末，以确定它们的活动是否能解释观察到的PAG刺激效应。
直接刺激PAG导致所有记录的肌肉活动发生显著变化，并以相位无关或相位依赖的方式重置呼吸节律。相比之下，用长或短时间尺度刺激分别刺激preBötC或pFL中的PAG终末，不能完全复制直接PAG刺激的效应，也不会产生任何呼吸重置。
我们的结果表明，PAG活动对呼吸的影响并非仅由PAG输入到preBötC或pFL介导，更可能涉及脑干区域更大网络的整合。
