Activation of 5-hydroxytryptamine type 3 receptor-expressing c-fiber vagal afferents inhibits retrotrapezoid nucleus chemoreceptors in rats

Retrotrapezoid nucleus (RTN) chemoreceptors are regulated by inputs from the carotid bodies (CB) and from pulmonary mechanoreceptors. Here we tested whether RTN neurons are influenced by 5-hydroxytryptamine type 3 receptor-expressing C-fiber vagal afferents. in urethan-anesthetized rats, selective activation of vagal C-fiber afferents by phenylbiguanide (PBG) eliminated the phrenic nerve discharge (PND) and inhibited RTN neurons (n = 24). PBG had no inhibitory effect in vagotomized rats. Muscimol injection into the solitary tract nucleus, commissural part, reduced inhibition of PND and RTN by PBG (73%), blocked activation of PND and RTN by CB stimulation (cyanide) but had no effect on inhibition of PND and RTN by lung inflation. Bilateral injections of muscimol into interstitial solitary tract nucleus (NTS) reduced the inhibition of PND and RTN by PBG (53%), blocked the inhibitory effects of lung inflation but did not change the activation of PND and RTN neurons by CB stimulation. PBG and lung inflation activated postinspiratory neurons located within the rostral ventral respiratory group (rVRG) and inhibited inspiratory and expiratory neurons. Bilateral injections of muscimol into rVRG eliminated PND and partially decreased RTN neuron inhibition by PBG (32%). in conclusion, activation of cardiopulmonary C-fiber afferents inhibits the activity of RTN chemoreceptors. the pathway relays within a broad medial region of the NTS and involves the rVRG to a limited degree. the apnea triggered by activation of cardiopulmonary C-fiber afferents may be due in part to a reduction of the activity of RTN chemoreceptors.Univ Virginia Hlth Syst, Dept Pharmacol, Charlottesville, VA 22908 USAUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, São Paulo, BrazilWeb of Scienc

Neural Control of Breathing and CO2 Homeostasis

Recent advances have clarified how the brain detects CO2 to regulate breathing (central respiratory chemoreception). These mechanisms are reviewed and their significance is presented in the general context of CO2/pH homeostasis through breathing. At rest, respiratory chemoreflexes initiated at peripheral and central sites mediate rapid stabilization of arterial PCO2 and pH. Specific brainstem neurons (e.g., retrotrapezoid nucleus, RTN; serotonergic) are activated by PCO2 and stimulate breathing. RTN neurons detect CO2 via intrinsic proton receptors (TASK-2, GPR4), synaptic input from peripheral chemoreceptors and signals from astrocytes. Respiratory chemoreflexes are arousal state dependent whereas chemoreceptor stimulation produces arousal. When abnormal, these interactions lead to sleep-disordered breathing. During exercise, central command and reflexes from exercising muscles produce the breathing stimulation required to maintain arterial PCO2 and pH despite elevated metabolic activity. The neural circuits underlying central command and muscle afferent control of breathing remain elusive and represent a fertile area for future investigation

Central Network Dynamics Regulating Visceral and Humoral Functions

The brain processes information from the periphery and regulates visceral and immune activity to maintain internal homeostasis, optimally respond to a dynamic external environment, and integrate these functions with ongoing behavior. In addition to its relevance for survival, this integration underlies pathology as evidenced by diseases exhibiting comorbid visceral and psychiatric symptoms. Advances in neuroanatomical mapping, genetically specific neuronal manipulation, and neural network recording are overcoming the challenges of dissecting complex circuits that underlie this integration and deciphering their function. Here we focus on reciprocal communication between the brain and urological, gastrointestinal, and immune systems. These studies are revealing how autonomic activity becomes integrated into behavior as part of a social strategy, how the brain regulates innate immunity in response to stress, and how drugs impact emotion and gastrointestinal function. These examples highlight the power of the functional organization of circuits at the interface of the brain and periphery

Central CO2 chemoreception and integrated neural mechanisms of cardiovascular and respiratory control

In this review, we ex-amine why blood pressure (BP) and sympathetic nerve activity (SNA) increase during a rise in central nervous system. (CNS) Pco 2 (central chemoreceptor stimulation). CNS acidification modifies SNA by two classes of mechanisms. The first one depends on the activation of the central respiratory controller (CRG) and causes the much-emphasized respiratory modulation of the SNA. The CRG prob-ably modulates SNA at several brain stem or spinal locations, but the most important site of interaction seems to be the caudal ventrolateral medulla (CVLM), where unidentified components of the CRG periodically gate the baroreflex. CNS Pco2 also influences sympathetic tone in a CRG-independent manner, and we propose that this process operates differently according to the level of CNS Pco2. In normocapnia and indeed even below the ventilatory recruitment threshold, CNS Pco2 exerts a tonic concentration-dependent excitatory effect on SNA that is plausibly mediated by specialized brain stem chemoreceptors such as the retrotrap-ezoid nucleus. Abnormally high levels of Pco2 cause an aversive interoceptive awareness in awake individuals and trigger arousal from sleep. These alerting responses presumably activate wake-promoting and/or stress-related pathways such as the orexinergic, noradrenergic, and serotonergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have brainwide projections that contribute to the CO 2-induced rise in breathing and SNA by facilitating neuronal activity at innumerable CNS locations. In the case of SNA, these sites include the nucleus of the solitary tract, the ventrolateral medulla, and the preganglionic neurons.8 page(s