Impaired chemosensory control of breathing after depletion of bulbospinal catecholaminergic neurons in rats
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Bulbospinal catecholaminergic neurons located in the rostral aspect of the ventrolateral medulla (C1 neurons) or within the ventrolateral pons (A5 neurons) are involved in the regulation of blood pressure and sympathetic outflow. A stimulus that commonly activates the C1 or A5 neurons is hypoxia, which is also involved in breathing activation. Although pharmacological and optogenetic evidence suggests that catecholaminergic neurons also regulate breathing, a specific contribution of the bulbospinal neurons to respiratory control has not been demonstrated. Therefore, in the present study, we evaluated whether the loss of bulbospinal catecholaminergic C1 and A5 cells affects cardiorespiratory control during resting, hypoxic (8% O2), and hypercapnic (7% CO2) conditions in unanesthetized rats. Thoracic spinal cord (T4-T8) injections of the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-SAP—2.4 ng/100 nl) and the retrograde tracer Fluor-Gold or ventrolateral pontine injections of 6-OHDA were performed in adult male Wistar rats (250–280 g, N = 7–9/group). Anti-DβH-SAP or 6-OHDA eliminated most bulbospinal C1 and A5 neurons or A5 neurons, respectively. Serotonergic neurons and astrocytes were spared. Depletion of the bulbospinal catecholaminergic cells did not change cardiorespiratory variables under resting condition, but it did affect the response to hypoxia and hypercapnia. Specifically, the increase in the ventilation, the number of sighs, and the tachycardia were reduced, but the MAP increased during hypoxia in anti-DβH-SAP-treated rats. Our data reveal that the bulbospinal catecholaminergic neurons (A5 and C1) facilitate the ventilatory reflex to hypoxia and hypercapnia.
KeywordsAnti-DβH-SAP C1 cells Hypercapnia Hypoxia 6-OHDA
This work was supported by the São Paulo Research Foundation (FAPESP; grants: 2014/22406-1 to ACT; 2015/23376-1 to TSM) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant: 471263/2013-3 to ACT and 471283/2012-6 to TSM). FAPESP fellowship (2014/07698-6 to MRML) and CNPq fellowship (301219/2016-8 to ACT and 301904/2015-4 to TSM).
MRML, ACT, and TSM designed the research; MRML and LTT performed the research; MRML, LTT, and TSM analyzed the data; and MRML, ACT, and TSM wrote the paper.
- 14.DePuy SD, Stornetta RL, Bochorishvili G, Deisseroth K, Witten I, Coates M, Guyenet PG (2013) Glutamatergic neurotransmission between the C1 neurons and the parasympathetic preganglionic neurons of the dorsal motor nucleus of the vagus. J Neurosci 33(4):1486–1497Google Scholar
- 16.Freiria-Oliveira AH, Blanch GT, Pedrino GR, Cravo SL, Murphy D, Menani JV, Colombari DS (2015) Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses. Am J Physiol Regul Integr Comp Physiol 309:R1082–R1091CrossRefPubMedGoogle Scholar
- 20.Guyenet PG (2014) Regulation of breathing and autonomic outflows by chemoreceptors. Compr Physiol 4(4):1511–1562Google Scholar
- 27.Kang JJ, Liang WH, Lam CS, Huang XF, Yang SJ, Wong-Riley MT, Fung ML, Liu YY (2016) Catecholaminergic neurons in synaptic connections with pre-Bötzinger complex neurons in the rostral ventrolateral medulla in normoxic and daily acute intermittent hypoxic rats. Exp Neurol 287:165–175CrossRefPubMedGoogle Scholar
- 29.Koshiya N, Guyenet PG (1994) A5 noradrenergic neurons and the carotid sympathetic chemoreflex. Am J Phys 267:R519–R526Google Scholar
- 36.Madden CJ, Ito S, Rinaman L, Wiley RG, Sved AF (1999) Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DbetaH-saporin. Am J Phys 277:R1063–R1075Google Scholar
- 42.Paxinos G & Watson C (1998). The rat brain in stereotaxic coordinatesGoogle Scholar
- 47.Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502(3):455–467Google Scholar
- 57.Takakura AC, Moreira TS (2011) Contribution of excitatory amino acid receptors of the retrotrapezoid nucleus to the sympathetic chemoreflex in rats. Exp Physiol 96(10):989–999Google Scholar
- 59.Takakura AC, Colombari E, Menani JV, Moreira TS (2011) Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats. Am J Physiol Regul Integr Comp Physiol 300(2):R501–510Google Scholar