Biology subjects

Zoccal, D. B.

Publications and source records attributed to Zoccal, D. B..

5 recordsLinked to original sources

bioRxiv2025

A comprehensive characterization of active expiration in freely behaving rats

Blood gas disturbances caused by exposure to low oxygen (hypoxia) or high carbon dioxide levels (hypercapnia) lead to a compensatory increase in pulmonary ventilation. Among the motor changes supporting these reflex respiratory responses is the recruitment of abdominal muscles (ABD) during the expiratory phase, which can enhance expiratory airflow or alter the duration of the expiratory phase. In this study, we assessed the functional impact of ABD recruitment on metabolic, motor, and ventilatory parameters in unanesthetized, freely behaving animals. Sprague-Dawley Holtzman male adult rats (n=7) were instrumented to perform simultaneous recordings of pulmonary ventilation, body temperature, diaphragmatic and ABD activities, and O2 consumption during exposure to various levels of hypoxia (12-8% O2) and hypercapnia (3-7% CO2). We observed that hypoxia or hypercapnia conditions evoked AE; however, ABD recruitment did not occur during the entire exposure period, displaying an intermittent profile. The occurrence of AE during hypoxia and hypercapnia conditions was linked to additional increases in tidal volume when compared to periods without ABD activity (P<0.05) and showed no associations with changes in diaphragmatic burst amplitude. Analyses of flow-like patterns suggested that AE during hypoxia recruited expiratory reserve volume during late expiration, while under hypercapnia, it accelerated lung emptying and increased the expiratory flow peak during post-inspiration. We also observed that AE was associated with an increase in oxygen consumption and did not improve air convection requirement, suggesting that this motor behavior may influence other aspects of respiration that potentially improve alveolar ventilation and gas exchange. Key points summaryO_LIAbdominal recruitment during the expiratory phase, known as active expiration (AE), emerges during blood gas disturbances to enhance pulmonary ventilation; however, the effect of AE on metabolic, motor, and ventilatory parameters in freely behaving animals exposed to hypoxia or hypercapnia remains uncertain. C_LIO_LIBy simultaneously recording pulmonary ventilation, diaphragmatic and abdominal activities, and O2 consumption, we found that the occurrence of AE during hypoxia or hypercapnia exposure resulted in an additional increase in tidal volume. C_LIO_LIAE was not evident during all periods of exposure to hypoxia or hypercapnia, and its expression increased O2 consumption. C_LIO_LIAnalysis of flow-like signals suggested that AE during hypoxia recruits expiratory reserve volume in late expiration, while under hypercapnia, it facilitates lung emptying and increases the peak expiratory flow post-inspiration. C_LIO_LIDespite being similar from a motor perspective, the impact of AE on lung ventilation differs between hypoxia and hypercapnia in unanesthetized rats. C_LI

physiology↗

bioRxiv2025

Prenatal cannabinoid exposure affects central cardiorespiratory control in young male and female rats

Cannabis use among pregnant women is rising globally, mainly for recreational and medical reasons to relieve symptoms like nausea, vomiting, anxiety, and insomnia. This trend is reinforced by the misconception that its natural origin guarantees safety, along with government policies promoting legalization. However, exposure to cannabinoids in utero can impact normal offsprings neurodevelopment and induce malfunctioning of various physiological systems, including the cardiorespiratory function. The present study investigated whether prenatal cannabinoid exposure disrupts the generation and control of autonomic and respiratory activities in early adulthood. Using in situ preparations of juvenile male and female rats (27-28 days old) exposed to a synthetic cannabinoid (WIN 55,212-2; 0.5 mg/kg/day, n=4-9) or vehicle (n=3-10) during gestation, we analyzed the activity of nerves innervating respiratory muscles and blood vessels. We noticed that females receiving WIN prenatally exhibited a reduced excitatory drive (post-inspiratory activity, post-I) to laryngeal muscles under resting conditions, suggesting impaired control of upper airway patency. Moreover, males and females exposed to WIN displayed reduced post-I and abdominal expiratory motor activities during stimulation of carotid body chemoreceptors (mimicking low oxygen situations) or exposure to high carbon dioxide levels, indicating an inability to mount appropriate reflex respiratory motor responses during blood gas disturbances. In addition, WIN-treated males showed attenuated sympathoexcitatory responses to carotid body activation or hypercapnia, evidencing a limited capacity to promote sympathetic-mediated hemodynamic changes. Thus, manipulating the fetal endocannabinoid system impacts the development of networks controlling respiratory and autonomic functions, leading to negative, long-term consequences for ventilation and cardiovascular function.

physiology↗

bioRxiv2023

The role of Kölliker-Fuse nucleus in breathing variability

The Kolliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apneas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupneic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. Key pointsThe Kolliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modeling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analyzing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide plausible hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

neuroscience↗

bioRxiv2021

The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex

Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we demonstrated that the TNF- receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF- increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where the majority of pre-sympathetic neurons reside. The activation of these neurons was accompanied by generalized activation of the sympathetic nervous system. Carotid body ablation blunted the TNF--induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF- administration were higher in rats subjected to either carotid body ablation or splanchnic sympathetic denervation. Collectively, our findings indicate that the carotid body detects circulating TNF- to activate a counteracting sympathetic anti-inflammatory mechanism.

neuroscience↗

bioRxiv2019

Inhibitory control of active expiration by the Botzinger complex in rats

The expiratory neurons of the Botzinger complex (BotC) provide inhibitory inputs to the respiratory network, which, during eupnea, are critically important for respiratory phase transition and duration control. Herein, we investigated how the BotC neurons interact with the expiratory oscillator located in the parafacial respiratory group (pFRG) and control the abdominal activity during active expiration. Using the decerebrated, arterially perfused in situ rat preparations, we recorded the neuronal activity and performed pharmacological manipulations of the BotC and pFRG during hypercapnia or after the exposure to short-term sustained hypoxia - conditions that generate active expiration. The experimental data were integrated in a mathematical model to gain new insights in the inhibitory connectome within the respiratory central pattern generator. Our results reveal a complex inhibitory circuitry within the BotC that provides inhibitory inputs to the pFRG thus restraining abdominal activity under resting conditions and contributing to abdominal expiratory pattern formation during active expiration.

physiology↗