HYPOXIA-INDUCED FOS EXPRESSION IN NEURONS PROJECTING TO THE PRESSOR REGION IN THE ROSTRAL VENTROLATERAL MEDULLA

Previous studies in anaesthetized animals have shown that the hypoxia- induced increase in sympathetic vasomotor activity is largely dependen t on synaptic excitation of sympathoexcitatory presser neurons in the rostral part of the ventrolateral medulla. The primary aim of this stu dy was to determine, in conscious rabbits, the distribution of neurons within the brain that have properties characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary pre sser region in response to systemic hypoxia. In a preliminary operatio n; a retrogradely-transported tracer, fluorescent-labelled microsphere s, was injected into the physiologically-identified presser region in the rostral ventrolateral medulla. After a waiting period of one to tw o weeks, the conscious rabbits were subjected to moderate hypoxia (ind uced by breathing 10% O-2 in N-2) for a period of 60 min. Control grou ps of animals were exposed to room air or to mild hypoxia (12% O-2 in N-2). Moderate hypoxia resulted in a modest hypertension of approximat ely 15 mmHg, and in the expression of Fos (a marker of neuronal activa tion) in many neurons in the nucleus tractus solitarius, the rostral, intermediate and caudal parts of the ventrolateral medulla, the Kollik er-Fuse nucleus, locus coeruleus, subcoeruleus and A5 area in the pens as well as in several midbrain and forebrain regions, including the p eriaqueductal grey in the midbrain and the paraventricular, supraoptic and arcuate nuclei in the hypothalamus. Fos expression was also obser ved in these regions in rabbits subjected to mild hypoxia or normoxia, but it was much reduced compared to rabbits subjected to moderate hyp oxia. Approximately half of the neurons in the ventrolateral medulla, 27% of neurons in the nucleus tractus solitarius, and 49-81% of neuron s in the locus coeruleus, sub-coeruleus and A5 area that expressed Fos following moderate hypoxia were also immunoreactive For tyrosine hydr oxylase, and were therefore catecholamine cells. Approximately half of the neurons in the nucleus tractus solitarius and two-thirds of neuro ns in the Kolliker-Fuse nucleus that expressed Fos following moderate hypoxia were retrogradely labelled from the rostral ventrolateral medu llary presser region. Similarly, approximately one quarter of Fos-posi tive cells in the caudal and intermediate ventrolateral medulla were r etrogradely labelled, but very few Fos-positive/retrogradely-labelled cells were found in other pontomedullary or suprapontine brain regions . The results indicate that systemic hypoxia results in activation of neurons in several discrete nuclei in the brainstem and forebrain, inc luding neurons in all the major pontomedullary catecholamine cell grou ps. However, neurons that are activated by systemic hypoxia and that a lso project to the rostral ventrolateral medullary pressor region are virtually confined to the lower brainstem, primarily in the nucleus tr actus solitarius and Kolliker-Fuse nucleus and to a lesser extent the caudal/intermediate ventrolateral medulla. In a previous study from ou r laboratory, we determined the distribution of neurons in the brainst em that are activated by hypertension and that also project to the ros tral ventrolateral medullary presser region. [Poison et ni. (1995) Neu roscience 67, 107-123]. Comparison of the present results with those f rom this previous study indicates that the hypoxia-activated neurons i n the nucleus tractus solitarius and Kolliker-Fuse nucleus that projec t to the rostral ventrolateral medulla are likely to be interneurons c onveying excitatory chemoreceptor signals, while those in the caudal/i ntermediate ventrolateral medulla are likely to be mainly interneurons conveying inhibitory baroreceptor signals, activated by the rise in a rterial blood pressure associated with the hypoxia-induced hypertensio n. (C) 1997 IBRO. Published by Elsevier Science Ltd.