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Variations in arousal levels can impact respiratory patterns. The mechanisms by which breathing behaviors can influence arousal state is not fully understood. In this study, we investigated the role of astrocytes in the preBötzinger complex (preBötC) in modulating arousal states via breathing in adult conscious rats. Using viral vector tools, we selectively interfered with astrocytic signaling in the preBötC. Rats with inhibited astrocytic signaling exhibited slower breathing rates and behaviors indicative of a calmer state, whereas enhanced purinergic signaling in preBötC astrocytes led to faster breathing and heightened arousal. Our findings reveal a key role for an astrocyte-mediated mechanism in the preBötC that influences both respiratory behaviors and higher-order brain functions like arousal, suggesting a bidirectional link between breathing behaviors and mental states.

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RESUMEN

Variations in arousal levels can impact respiratory patterns. However, whether changes in breathing behaviors can influence arousal state is not fully understood. In this study, we investigated the role of astrocytes in the preBötzinger complex (preBötC) in modulating arousal states via breathing in adult conscious rats. Using viral vector tools, we selectively interfered with astrocytic signaling in the preBötC. Rats with inhibited astrocytic signaling exhibited slower breathing rates and behaviors indicative of a calmer state, whereas enhanced purinergic signaling in preBötC astrocytes led to faster breathing and heightened arousal. Our findings reveal a key role for astrocyte-mediated mechanism in the preBötC that influences both respiratory behaviors and higher-order brain functions like arousal, suggesting a bidirectional link between breathing behaviors and mental states.

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Central pattern generators (CPGs) generate the rhythmic and coordinated neural features necessary for the proper conduction of complex behaviors. In particular, CPGs are crucial for complex motor behaviors such as locomotion, mastication, respiration, and vocal production. While the importance of these networks in modulating behavior is evident, the mechanisms driving these CPGs are still not fully understood. On the other hand, accumulating evidence suggests that astrocytes have a significant role in regulating the function of some of these CPGs. Here, we review the location, function, and role of astrocytes in locomotion, respiration, and mastication CPGs and propose that, similarly, astrocytes may also play a significant role in the vocalization CPG.

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The respiratory system maintains homeostatic levels of oxygen (O2) and carbon dioxide (CO2) in the body through rapid and efficient regulation of breathing frequency and depth (tidal volume). The commonly used methods of analyzing breathing data in behaving experimental animals are usually subjective, laborious, and time-consuming. To overcome these hurdles, we optimized an analysis toolkit for the unsupervised study of respiratory activities in animal subjects. Using this tool, we analyzed breathing behaviors of the common marmoset (Callithrix jacchus), a New World non-human primate model. Using whole-body plethysmography in room air as well as acute hypoxic (10% O2) and hypercapnic (6% CO2) conditions, we describe breathing behaviors in awake, freely behaving marmosets. Our data indicate that marmosets' exposure to acute hypoxia decreased metabolic rate and increased sigh rate. However, the hypoxic condition did not augment ventilation. Hypercapnia, on the other hand, increased both the frequency and depth (i.e., tidal volume) of breathing.

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BACKGROUND: Postoperative pain after arthroscopic rotator cuff repair (RCR) is difficult to predict and manage. The experience of pain is thought to be influenced by a range of different factors. Determining which patient factors contribute to the pain may help us to better understand and manage it. PURPOSE: To evaluate the preoperative patient characteristics that may be predictive of, and correlated with, postoperative pain after arthroscopic RCR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study evaluated 2172 patients who underwent an arthroscopic RCR between February 2004 and December 2015. Pain frequency and severity were measured preoperatively and at 6 weeks after surgery using a modified L'Insalata questionnaire with Likert scales. This 6-week time point was chosen as previous studies have shown patients rank this time point as high in terms of pain after RCR. Logistic regression analysis was conducted to examine the relationship between postoperative pain scores and preoperative pain scores, age, sex, tear size, strength, level of sporting and work activity, and work-related injury status. RESULTS: The severity of preoperative pain at night (r = 0.33; P < .001), preoperative pain at rest (r = 0.32; P < .001), and frequency of extreme pain (r = 0.31; P < .001) were the strongest independent associations with the frequency of pain at 6 weeks postoperatively. Other associations with postoperative pain frequency included reduced liftoff strength (r = -0.21; P < .001), work-related injury status (P < .001), younger age (P = .001), and female sex (P = .04). Tear size was inversely related with pain severity (R2 = 0.85). The severity of preoperative pain had the strongest independent association with the severity of postoperative pain at 6 weeks after surgery (r = 0.35; P < .001). Other associations with postoperative pain severity included increased patient-ranked preoperative stiffness (P < .001), a poorer impression of one's shoulder (P < .001), reduced level of sporting activity (P < .001), and work-related injury status (P < .001). CONCLUSION: Multiple risk factors have been identified for postoperative pain after RCR, the strongest of which is preoperative pain. However, of note, the magnitude of the correlations between preoperative severity and frequency of pain and postoperative severity and frequency of pain were found to be weak to moderate (r = 0.30-0.35). This suggests that while preoperative pain and its severity are associated with postoperative pain, other factors are likely involved in predicting pain. Smaller tear size, younger age, female sex, and work-related injuries were also associated with postoperative pain at 6 weeks after surgery.

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