Breathing stability during sleep and during hypercapnia is dependent on the retrotrapezoid nucleus in adult mice
| Autor: | George Souza, Daniel Stornetta, Douglas Bayliss, Stephen Abbott |
|---|---|
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Physiology. 38 |
| ISSN: | 1548-9221 1548-9213 |
| Popis: | Background: Eupneic breathing during sleep is determined by the chemical drive arising from central and peripheral chemoreceptors. The retrotrapezoid nucleus (RTN) contains chemoreceptor neurons that are proposed to be critical for ventilatory responses to CO2. RTN chemoreceptor neurons can be identified by expression of transcripts for Neuromedin B ( Nmb+). We hypothesized that the ablation of RTN Nmb+ neurons cause alveolar hypoventilation at rest and breathing instability during sleep. Normally, in intact subjects, increasing respiratory drive with hypercapnia produces a robust and more stable breathing pattern compared to resting condition. We furhter hypothesized that in the absence of RTN, hypercapnia will not increase breathing stability and the ventilatory response to CO2 will be impaired. Methods: Bilateral microinjections of a designer cell-ablation virus, AAV5-Flex-Casp3-TEVP, were placed in the RTN in heterozygous Cre-positive (RTN lesion) and Cre-negative (controls) Nmb-Cre mice and EEG/neck EMG electrodes were implanted. One month later, mice were tested in an unrestrained plethysmography chamber for breathing and sleep/wake recordings in normoxic conditions. Mice were exposed to hyperoxic hypercapnia (FICO2 up to 0.09) to assess the central respiratory CO2 chemoreflex after RTN lesion. Arterial blood gases were also collected in unrestrained unanesthetized conditions. Values are presented as mean ±SD. Results: Ablation of the RTN was complete (+ neurons remaining in RTN lesion group) and selective based on counts of neighboring catecholaminergic and serotonergic neurons. Arterial PCO2 was increased in RTN-lesion mice (n=6) compared to controls (n=7) (49 ± 5 vs. 39 ± 3 mmHg, p2 was reduced (75 ± 11 vs. 89 ± 7 mmHg, p=0.019). Minute-ventilation was reduced in RTN-lesion mice (n=13) compared to control (n=13) (1.7 ± 0.4 vs. 2.4 ± 0.3 mL/min/g, p2 was attenuated in RTN lesion mice compared to controls (3.2 ±1 vs. 10.4 ±2 mL/min/g at FICO2 0.09, p This work is funded by National Institutes of Health, R01HL148004 to Stephen BG Abbott and R01HL108609 to Douglas A Bayliss. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|