Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Abstract

Cardiorespiratory activity is controlled by a network of neurons located within the lower brainstem. The basic rhythm of breathing is generated by neuronal circuits within the medullary pre-Bö tzinger complex, modulated by pontine and other inputs from cell groups within the medulla oblongata and then transmitted to bulbospinal pre-motor neurons that relay the respiratory pattern to cranial and spinal motor neurons controlling respiratory muscles. Cardiovascular sympathetic and vagal activities have characteristic discharges that are patterned by respiratory activity. This patterning ensures ventilation-perfusion matching for optimal respiratory gas exchange within the lungs. Peripheral arterial chemoreceptors and central respiratory chemoreceptors are crucial for the maintenance of cardiorespiratory homeostasis. Inputs from these receptors ensure adaptive changes in the respiratory and cardiovascular motor outputs in various environmental and physiological conditions. Many of the connections in the reflex pathway that mediates the peripheral arterial chemoreceptor input have been established. The nucleus tractus solitarii, the ventral respiratory network, presympathetic circuitry and vagal pre-ganglionic neurons at the level of the medulla oblongata are integral components, although supramedullary structures also play a role in patterning autonomic outflows according to behavioural requirements. These medullary structures mediate cardiorespiratory reflexes that are initiated by the carotid and aortic bodies in response to acute changes in PO 2 , PCO 2 and pH in the arterial blood. The level of arterial PCO 2 is the primary factor in determining respiratory drive and although there is a significant role of the arterial chemoreceptors, the principal sensor is located either at or in close proximity to the ventral surface of the medulla. The cellular and molecular mechanisms of central chemosensitivity as well as the neural basis for the integration of central and peripheral chemosensory inputs within the medulla remain challenging issues, but ones that have some emerging answers.

Widespread depolarization during expiration: A source of respiratory drive?

“…the brainstem and respiratory neurons in the central pattern generator produce synaptic drive for neurons that control respiratory muscles [9]. It has also been established that respiratory drive derives from detection of high carbon dioxide levels by peripheral chemoreceptors and receptors in the medulla [10]. There is also the theory of hypoxic drive, a form of respiratory drive, in which the medulla detects low levels of oxygen rather than high levels of carbon dioxide, resulting in the drive to breathe [11].…”

“…Peripheral chemoreceptors detect elevated levels of CO 2 in the blood which stimulate the respiratory center to stimulate respiratory muscles to breathe [10]. There is also the debated existence of hypoxic drive, in individuals with compromised respiratory function, in which the body uses oxygen chemoreceptors rather than CO 2 chemoreceptors [11].…”

Mecanismos purinérgicos no bulbo ventrolateral rostral modulam respostas cardiovasculares e respiratórias promovidas pela ativação dos quimiorreceptores centrais e periféricos.

“…For these experiments, we targeted the raphe pallidus (RPa; n = 6) and the parapyramidal region (Ppy) (n = 5) because serotonergic cells in these regions reportedly function as chemoreceptors (Richerson, 2004) and are thought to be located within diffusion distance (estimated to be ß400 μm from the ventral surface; Spyer & Gourine, 2009) from sites of CO 2 /H + -evoked ATP release on the ventral surface. Injections of PPADS were placed bilaterally in the medullary raphe in these rats (Fig.…”

Neurônios catecolaminérgicos do tronco encefálico participam dos ajustes respiratórios induzidos por hipóxia e hipercapnia.

“…A porção ventrolateral do bulbo (VLM) está localizada no quadrante ventrolateral da formação reticular bulbar, sendo delimitada, em sua porção rostral, pela porção caudal do núcleo motor do facial (VII) e, em sua porção caudal, pela porção compacta do núcleo ambíguos (NA) (Ilustração 1A) (Spyer, Gourine, 2009;Guyenet et al, 2013). O VLM é subdividido em três porções: rostral, intermediária e caudal, sendo, respectivamente, denominadas de bulbo ventrolateral rostral (RVLM), bulbo ventrolateral intermediário (IVLM) e bulbo ventrolateral caudal (CVLM).…”

“…O VLM é subdividido em três porções: rostral, intermediária e caudal, sendo, respectivamente, denominadas de bulbo ventrolateral rostral (RVLM), bulbo ventrolateral intermediário (IVLM) e bulbo ventrolateral caudal (CVLM). Nestas regiões, estão localizados diversos grupamentos neuronais envolvidos no controle cardiovascular e respiratório (Spyer, Gourine, 2009;Smith et al, 2013 …”