Acute hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the C1 region

• Published in: Experimental neurology 2016-11, Vol.285 (Pt A), p.1-11
• Main Authors: Silva, Talita M., Takakura, Ana C., Moreira, Thiago S.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Blood Pressure - physiology; C1 region; Catecholamines - metabolism; Cell Count; Cholera Toxin - pharmacokinetics; Disease Models, Animal; Drug Administration Schedule; Glutamate Decarboxylase - metabolism; Heart Rate - physiology; Hypothalamic paraventricular nucleus; Hypoxia; Hypoxia - pathology; Hypoxia - physiopathology; Male; Medulla Oblongata - pathology; Neural Pathways - physiology; Neurons - physiology; Oncogene Proteins v-fos - metabolism; Paraventricular Hypothalamic Nucleus; Peripheral chemoreflex; Phytohemagglutinins - administration & dosage; Phytohemagglutinins - pharmacokinetics; Rats; Rats, Wistar; Tyrosine 3-Monooxygenase - metabolism; Vesicular Glutamate Transport Protein 2 - metabolism
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2016.08.016

Catecholaminergic C1 cells reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM) and can be activated by hypoxia. These neurons regulate the hypothalamic pituitary axis via direct projections to the hypothalamic paraventricular nucleus (PVH) and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. Based on the various effects attributed to the C1 cells and what is currently known of their synaptic inputs, our hypothesis is that acute hypoxia (AH) activates RVLM projecting catecholaminergic neurons to PVH. Anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) was unilaterally injected into the RVLM and a retrograde tracer Cholera toxin b (CTb) was unilaterally injected into the PVH region. After ten days, male Wistar rats that received CTb injection into the PVH were subjected to AH (8% O2, balanced with N2) or normoxia (21% O2) for 3h. Acute hypoxia significantly increased Fos immunoreactivity in the C1 region (68±2 neurons), and half of the RVLM cells activated are catecholaminergic (35±2 neurons). We observed that 23±4% of the RVLM projecting PVH cells that were activated by AH were also C1 cells. The presence of varicosities containing PHA-L in PVH region was also observed. The present results suggest that catecholaminergic C1-PVH projection is hypoxia-sensitive and the pathway between these two important brain areas can be one more piece in the complex puzzle of neural control of autonomic regulation during hypoxia. •C1 neurons in the ventrolateral medulla are activated by hypoxia and project to PVH.•C1 neurons activate the PVH monosynaptically by releasing glutamate.•C1 cells recruited by hypoxia produce a repertoire of autonomic responses.