Role of midbrain in the control of breathing in anuran amphibians

The present study was designed to explore systematically the midbrain of unanesthetized, decerebrate anuran amphibians (bullfrogs), using chemical and electrical stimulation and midbrain transections to identify sites capable of exciting and inhibiting breathing. Ventilation was measured as fictive motor output from the mandibular branch of the trigeminal nerve and the laryngeal branch of the vagus nerve. The results of our transection studies suggest that, under resting conditions, the net effect of inputs from sites within the rostral half of the midbrain is to increase fictive breathing frequency, whereas inputs from sites within the caudal half of the midbrain have no net effect on fictive breathing frequency but appear to act on the medullary central rhythm generator to produce episodic breathing. The results of our stimulation experiments indicate that the principal sites in the midbrain that are capable of exciting or inhibiting the fictive frequency of lung ventilation, and potentially clustering breaths into episodes, appear to be those primarily involved in visual and auditory integration, motor functions, and attentional state.

Nucleus isthmi and control of breathing in amphibians

Despite recent advances, the mechanisms of neurorespiratory control in amphibians are far from understood. One of the brainstem structures believed to play a key role in the ventilatory control of anuran amphibians is the nucleus isthmi (NI). This nucleus is a mesencephalic structure located between the roof of the midbrain and the cerebellum, which differentiates during metamorphosis; the period when pulmonary ventilation develops in bullfrogs. It has been recently suggested that the NI acts to inhibit hypoxic and hypercarbic drives in breathing by restricting increases in tidal volume. This data is similar to the influence of two pontine structures of mammals, the locus coeruleus and the nucleus raphe magnus. The putative mediators for this response are glutamate and nitric oxide. Microinjection of kynurenic acid (an ionotropic receptor antagonist of excitatory amino acids) and L-NAME (a non-selective NO synthase inhibitor) elicited increases in the ventilatory response to hypoxia and hypercarbia. This article reviews the available data on the role of the NI in the control of ventilation in amphibians. (C) 2004 Elsevier B.V. All rights reserved.

Control of breathing in anuran amphibians

The primary role of the respiratory system is to ensure adequate tissue oxygenation, eliminate carbon dioxide and help to regulate acid-base status. To maintain this homeostasis, amphibians possess an array of receptors located at peripheral and central chemoreceptive sites that sense respiration-related variables in both internal and external environments. As in mammals, input from these receptors is integrated at central rhythmogenic and pattern-forming elements in the medulla in a manner that meets the demands determined by the environment within the constraints of the behavior and breathing pattern of the animal. Also as in mammals, while outputs from areas in the midbrain may modulate respiration directly, they do not play a significant role in the production of the normal respiratory rhythm. However, despite these similarities, the breathing patterns of the two classes are different: mammals maintain homeostasis of arterial blood gases through rhythmic and continuous breathing, whereas amphibians display an intermittent pattern of aerial respiration. While the latter is also often rhythmic, it allows a degree of fluctuation in key respiratory variables that has led some to suggest that control is not as tight in these animals. In this review we will focus specifically on recent advances in studies of the control of ventilation in anuran amphibians. This is the group of amphibians that has attracted the most recent attention from respiratory physiologists. (c) 2006 Elsevier B.V. All rights reserved.

Control of breathing and blood pressure by parafacial neurons in conscious rats

New Findings: • What is the central question of this study? The main purpose of the present manuscript was to investigate the cardiorespiratory responses to hypoxia or hypercapnia in conscious rats submitted to neuronal blockade of the parafacial region. We clearly showed that the integrity of parafacial region is important for the respiratory responses elicited by peripheral and central chemoreflex activation in freely behavior rats. • What is the main finding and its importance? Since the parafacial region is part of the respiratory rhythm generator, they are essential for postnatal survival, which is probably due to their contribution to chemoreception in conscious rats. The retrotrapezoid nucleus (RTN), located in the parafacial region, contains glutamatergic neurons that express the transcriptor factor Phox2b and that are suggested to be central respiratory chemoreceptors. Studies in anaesthetized animals or in vitro have suggested that RTN neurons are important in the control of breathing by influencing respiratory rate, inspiratory amplitude and active expiration. However, the contribution of these neurons to cardiorespiratory control in conscious rats is not clear. Male Holtzman rats (280-300 g, n= 6-8) with bilateral stainless-steel cannulae implanted into the RTN were used. In conscious rats, the microinjection of the ionotropic glutamatergic agonist NMDA (5 pmol in 50 nl) into the RTN increased respiratory frequency (by 42%), tidal volume (by 21%), ventilation (by 68%), peak expiratory flow (by 24%) and mean arterial pressure (MAP, increased by 16 ± 4, versus saline, 3 ± 2 mmHg). Bilateral inhibition of the RTN neurons with the GABAA agonist muscimol (100 pmol in 50 nl) reduced resting ventilation (52 ± 34, versus saline, 250 ± 56 ml min-1 kg-1 with absolute values) and attenuated the respiratory response to hypercapnia and hypoxia. Muscimol injected into the RTN slightly reduced resting MAP (decreased by 13 ± 7, versus saline, increased by 3 ± 2 mmHg), without changing the effects of hypercapnia or hypoxia on MAP and heart rate. The results suggest that RTN neurons activate facilitatory mechanisms important to the control of ventilation in resting, hypoxic or hypercapnic conditions in conscious rats. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.

Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Control of cardiorespiratory function in response to hypoxia in an air-breathing fish, the African sharptooth catfish, Clarias gariepinus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Autonomic control of post-air-breathing tachycardia in Clarias gariepinus

The African catfish (Clarias gariepinus) is a teleost with bimodal respiration that utilizes a paired suprabranchial chamber located in the gill cavity as an air-breathing organ. Like all air-breathing fishes studied to date, the African catfish exhibits pronounced changes in heart rate (f H) that are associated with air-breathing events. We acquired f H, gill-breathing frequency (f G) and air-breathing frequency (f AB) in situations that require or do not require air breathing (during normoxia and hypoxia), and we assessed the autonomic control of post-air-breathing tachycardia using an infusion of the β-adrenergic antagonist propranolol and the muscarinic cholinergic antagonist atropine. During normoxia, C. gariepinus presented low f AB (1.85 ± 0.73 AB h−1) and a constant f G (43.16 ± 1.74 breaths min−1). During non-critical hypoxia (PO2 = 60 mmHg), f AB in the African catfish increased to 5.42 ± 1.19 AB h−1 and f G decreased to 39.12 ± 1.58 breaths min−1. During critical hypoxia (PO2 = 20 mmHg), f AB increased to 7.4 ± 1.39 AB h−1 and f G decreased to 34.97 ± 1.78 breaths min−1. These results were expected for a facultative air breather. Each air breath (AB) was followed by a brief but significant tachycardia, which in the critical hypoxia trials, reached a maximum of 143 % of the pre-AB f H values of untreated animals. Pharmacological blockade allowed the calculation of cardiac autonomic tones, which showed that post-AB tachycardia is predominantly regulated by the parasympathetic subdivision of the autonomic nervous system.

Autonomic control of post-air-breathing tachycardia in Clarias gariepinus (Teleostei: Clariidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Control of respiration in fish, amphibians and reptiles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Autonomic control of cardiorespiratory interactions in fish, amphibians and reptiles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Branchial O2 chemoreceptors in Nile tilapia Oreochromis niloticus: Control of cardiorespiratory function in response to hypoxia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Respiratory manifestations of panic disorder in animals and humans: A unique opportunity to understand how supramedullary structures regulate breathing

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)