ACETYLCHOLINE AND CENTRAL RESPIRATORY CONTROL - PERTURBATIONS OF ACETYLCHOLINE SYNTHESIS IN THE ISOLATED BRAIN-STEM OF THE NEONATAL RAT

The brainstem neurochemical processes which support spontaneous ventil ation are not known. Cholinergic transmission may play an important ro le. If this is true, perturbations in acetylcholine (ACh) turnover sho uld alter ventilatory output in a predictable manner. Using the isolat ed superfused brainstem-spinal axis from the neonatal rat, the effects of modifiers of ACh synthesis on spontaneous C-4 (phrenic) output wer e determined. S-Bromopyruvate and hydroxycitrate, inhibitors of acetyl -CoA (substrate for ACh synthesis) formation, caused depression of the C-4 output in a dose-dependent manner when added to the superfusate. Triethylcholine, a false-transmitter generating choline analog, caused a similar depression. Citrate, a cytosolic precursor to acetyl-CoA fo rmation, caused stimulation of C-4 (phrenic) output. The stimulatory e ffects of citrate were blocked by the muscarinic cholinergic blocker, atropine. These findings are consistent with the view that the ACh syn thetic pathway provides a continuous and important input to the normal brainstem elements that support ventilation.