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

Silva, TM;Takakura, AC;Moreira, TS;

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 (682 neurons), and half of the RVLM cells activated are catecholaminergic (352 neurons). We observed that 234% 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.