Distinct inspiratory rhythm and pattern generating mechanisms in the preBötzinger complex.

In the mammalian respiratory central pattern generator, the preBötzinger complex (preBötC) produces rhythmic bursts that drive inspiratory motor output. Cellular mechanisms initiated by each burst are hypothesized to be necessary to determine the timing of the subsequent burst, playing a critical role in rhythmogenesis. To explore mechanisms relating inspiratory burst generation to rhythmogenesis, we compared preBötC and hypoglossal (XII) nerve motor activity in medullary slices from neonatal mice in conditions where periods between successive inspiratory XII bursts were highly variable and distributed multimodally. This pattern resulted from rhythmic preBötC neural population activity that consisted of bursts, concurrent with XII bursts, intermingled with significantly smaller "burstlets". Burstlets occurred at regular intervals during significantly longer XII interburst intervals, at times when a XII burst was expected. When a preBötC burst occurred, its high amplitude inspiratory component (I-burst) was preceded by a preinspiratory component that closely resembled the rising phase of burstlets. Cadmium (8 μM) eliminated preBötC and XII bursts, but rhythmic preBötC burstlets persisted. Burstlets and preinspiratory activity were observed in ~90% of preBötC neurons that were active during I-bursts. When preBötC excitability was raised significantly, burstlets could leak through to motor output in medullary slices and in vivo in adult anesthetized rats. Thus, rhythmic bursting, a fundamental mode of nervous system activity and an essential element of breathing, can be deconstructed into a rhythmogenic process producing low amplitude burstlets and preinspiratory activity that determine timing, and a pattern-generating process producing suprathreshold I-bursts essential for motor output

Opioid-resistant respiratory pathway from the preinspiratory neurones to abdominal muscles: in vivo and in vitro study in the newborn rat

We report that after spontaneous breathing movements are stopped by administration of opioids (opioid-induced apnoea) in neonatal rats, abdominal muscles continue to contract at a rate similar to that observed during periods of ventilation. Correspondingly, in vitro bath application of a μ opioid receptor agonist suppresses the activity of the fourth cervical root (C4) supplying the diaphragm, but not the rhythmic activity of the first lumbar root (L1) innervating the abdominal muscles. This indicates the existence of opioid-resistant rhythmogenic neurones and a neuronal pathway transmitting their activity to the abdominal motoneurones. We have investigated this pathway by using a brainstem-spinal cord preparation of the neonatal rat. We identified bulbospinal neurones with a firing pattern identical to that of the L1 root. These neurones were located caudal to the obex in the vicinity of the nucleus retroambiguus. Resting potentials ranged from -49 to -40 mV (mean ± s.d. -44.0 ± 4.3 mV). The mean input resistance was 315.5 ± 54.8 MΩ. The mean antidromic latency from the L1 level was 42.8 ± 4.4 ms. Axons crossed the midline at the level of the cell body. The activity pattern of the bulbospinal neurones and the L1 root consisted of two bursts per respiratory cycle with a silent period during inspiration. This pattern is characteristic of preinspiratory neurones. We found that 11 % of the preinspiratory neurones projected to the area where the bulbospinal neurones were located. These preinspiratory neurones were found in the rostral ventrolateral medulla close (200-350 μm) to the ventral surface at the level of the rostral half of the nucleus retrofacialis. Our data suggest the operation of a disynaptic pathway from the preinspiratory neurones to the L1 motoneurones in the in vitro preparation. We propose that the same pathway is responsible for rhythmic activation of the abdominal muscles during opioid-induced apnoea in the newborn rat