CO2-induced c-fos expression in the CNS catecholaminergic neurons

In these studies we examined c-fos expression in catecholaminergic neurons following exposure of unanesthetized rats to hypercapnic stress. Breathing a gas mixture with elevated CO2 (15% CO2, 21% O2 and 64% N2, or 15% CO2 balance O2) for 60 min, induced activation of the c-fos gene in widespread regions of the CNS, as indicated by the expression of Fos-like immunoreactive protein (Fos). Similar results were obtained in carotid body denervated animals. Colocalization studies of tyrosine hydroxylase (TH) and Fos protein revealed that in the brainstem, 73 to 85% of noradrenaline-containing cells expressed Fos immunoreactivity. Double-labeled neurons were found in the ventrolateral medullary reticular formation (A1 noradrenaline cells), in the dorsal aspect of medulla oblongata (A2 noradrenaline cells), in the ventrolateral pons (A5 noradrenaline cells), and in the locus coeruleus (A6 noradrenaline cells). However, over 90% of TH-immunoreactive neurons in the mesencephalon and diencephalon (dopaminergic cells) did not express Fos-like immunoreactivity in response to CO2. These results indicate that the brainstem noradrenaline-containing neurons are part of the neuronal networks that react to hypercapnic exposure.