Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Abstract

Developmental changes in the respiratory activity and its modulation by substance P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from the day of birth to day 3 (P0-P3). The respiratory network activity in the ventrolateral medulla was represented by two types of bursts: basic regular bursts with typical decrementing shape and biphasic bursts appearing after augmented biphasic discharges in inspiratory neurons. With advancing postnatal age the respiratory output was considerably modified; the basic rhythm became faster by 20%, whereas the biphasic burst rate, which was originally 15 times slower, declined further by 180% and the C4 burst duration significantly decreased by 20% due to reduced decay time without preceding changes in the central inspiratory drive. SP had an age-dependent excitatory effect on respiratory activity. In the basic rhythm, SP could induce transient rhythm cessations on P0-P2 but not on P3. For the biphasic burst frequency, the sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP-induced changes increased. In both types of bursts, SP prolonged C4 burst duration due to increasing decay time. This effect was three times greater on P3 and did not depend on the central inspiratory drive. Our results suggest that the potency of SP to regulate the respiratory activity elevates during the early postnatal period. The developmental changes in the respiratory activity appear to represent the transient stage in the maturation of rhythm and pattern generation mechanisms facilitating adaptive behavior of a quickly growing organism.

Postnatal conversion of cross phrenic activity from an active to latent state

“…This finding is supported by a previous report which shows that the basic frequency of respiratory rhythm increases and becomes faster from P0 to P3 in rat brainstem-spinal cord preparations (Shvarev and Lagercrantz, 2006). Since there are significant changes in frequency between injured and non-injured animals within specific time groups, this suggests that the hemisection injury induced the change of respiratory frequency.…”

“…However, the developmental pattern of respiratory frequency in the hemisected animals is the same as the non-hemisection controls. In general, the developmental change of the respiratory frequency suggests that the respiratory rhythm generation and the transformation by the motoneurons of rhythmic inspiratory drive into appropriate patterns of respiratory output continue to mature postnatally (Greer and Funk, 2005; Shvarev and Lagercrantz, 2006). …”

Dynamics of neuromodulatory feedback determines frequency modulation in a reduced respiratory network: A computational study

“…Thus, our model predicts that loss of the positive feedback from preBötC to Raphe will result in decreased frequency or even loss of rhythmicity for some degrees of neuromodulatory tone. It has been shown that in the neonatal rat brainstem-spinal cord preparation, the effects of SP can be biphasic at the very early age (P0–P1), with an initial drop or even cessation of the rhythm and prolonged period of increased frequency (Shvarev and Lagercrantz, 2006). This finding is identical to results of our model for the weak feedback strengths.…”

“…For more mature preparations (P2–P3) SP did not induce a decrease in respiratory frequency, which is similar to our modeling results for larger values of positive feedback. Therefore, one possible interpretation of Shvarev and Lagercrantz (2006) experiments for early post-natal experiment is an increase in positive feedback between the Raphe and preBötC during the first few days of postnatal life. It has been reported that victims of sudden infant death syndrome (SIDS) have multiple defects in the serotonergic system (Duncan et al, 2010; Paterson et al, 2009).…”

Substance P/Neurokinin 1 and Trigeminal System: A Possible Link to the Pathogenesis in Sudden Perinatal Deaths

“…Under increasing hypoxia, SP manifests as natural anti-hypoxant and is not only involved in nociception mechanisms but also in brain adaptation to oxygen deficiency (40). SP-ergic system was found to be more active in regulating the respiratory responses during the early postnatal period in neonatal rat brainstem–spinal cord preparation (41) and medullary slice preparations of newborn mice (42). But surprisingly, SP was not found to control ventilatory rhythm generation in fetal rats, and it was hypothesized that, may be, SP does not modulate the generation of respiratory responses before birth and affects the phrenic motoneurons only after birth (43).…”