Despite new developments, there remains a significant need for better therapies with improved long-term efficacy and decreased toxicity.

The pre-Bötzinger Complex (preBötC) inspiratory centre remains active in isolated brainstem-spinal cords and brainstem slices. The extent to which findings in these models depend on their dimensions or superfusate [K + ] and [Ca 2+ ] (both of which determine neuronal excitability) is not clear. We report here that inspiratory-related rhythms in newborn rat slices and brainstem-spinal cords with defined boundaries were basically similar in physiological Ca 2+ (1.2 mM) and K + (3 mM). Hypoglossal nerve rhythm was 1 : 1-coupled to preBötC activity in slices and to cervical nerve bursts in en bloc preparations lacking the facial motonucleus (VII). Hypoglossal rhythm was depressed in brainstems containing (portions of) VII, while pre/postinspiratory lumbar nerve bursting was present only in preparations with > 79% VII. preBötC-related slice rhythms were inhibited in 1.5 mM Ca 2+ solution, whereas their longevity and burst rate were substantially augmented in 1 mM Ca 2+ . Ca 2+ depression of slice rhythms was antagonized by raising superfusate K + to 8-10 mM. This strong extracellular Ca 2+ /K + antagonism of inspiratory (motor) rhythms was also revealed in brainstem-spinal cords without VII, while the inhibition was progressively attenuated with increasing amount of rostral tissue. We hypothesize that depression of hypoglossal rhythm and decreased Ca 2+ sensitivity of preBötC rhythm are probably not related to an increased content of rostral respiratory structures, but rather to larger brainstem dimensions resulting in interstitial gradients for neuromodulator(s) and K + , respectively. We discuss whether block of pre/postinspiratory activity in preparations with < 79% VII is due to impairment of the pathway from preinspiratory interneurons to abdominal muscles

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