Anatomical changes in selected cardio-respiratory brainstem nuclei following early post-natal chronic intermittent hypoxia

Early post-natal environmental exposures, including chronic intermittent hypoxia (CIH), may lead to long-term alterations in cardio-respiratory control, such as reductions in baroreflex sensitivity and acute hypoxic ventilatory responses in adult rats. Although the mechanisms underlying CIH-induced functional metaplasticity are unclear, anatomical alterations within selected brainstem nuclei may develop after CIH. To examine this issue, male rats were exposed to CIH (RAIH) or room air (RARA) for the first 30 days of life and were microinjected unilaterally in the right nodose ganglion with the neuronal tracer tetramethylrhodamine-dextran (TMR-D) to label brainstem neurons receiving vagal and glossopharyngeal projections. Substantial reductions in labeled afferents within the nucleus tractus solitarii (nTS) and significant increases in the total number of labeled neurons within the ventrolateral medulla (VLM), principally in the nucleus ambiguus (Namb; p < 0.01) occurred in RAIH. Furthermore, 5-bromo-2′deoxyuridine labeling revealed enhanced neurogenesis within the Namb in RAIH and could partially account for the increased neuronal population in Namb. Thus, CIH-associated cardio-respiratory metaplasticity is accompanied by substantial structural changes within both the nTS and Namb.