Abstract

Several key events in the development of the perinatal rat phrenic nerve and diaphragm have been determined, including the following: i) Fetal inspiratory motor discharge commences within the phrenic motoneuron (PMN) pool on embryonic day (E)17; gestation period is 21 days. ii) Phrenic axons grow to innervate the full extent of diaphragmatic musculature by E17-E18. iii) There is a radical maturation of PMN morphology during the period from E16-E20. We have subsequently gone on to examine functional changes by examining PMN electrophysiological and diaphragm contractile properties prior and subsequent to these pivotal developmental stages (E16-P0). Summary data will be presented demonstrating the following: 1) As PMNs develop from E16 to P0, there are changes in passive membrane properties; resting membrane potential becomes hyperpolarized by ~10 mV, the input resistance decreases ~3-fold, and the mean rheobase increases by a factor of ~2.6. 2) There are significant changes in the amplitude, duration and the afterpotentials of action potentials from E16-P0 which places restrictions on the repetitive firing patterns of fetal PMNs. 3) The changes in PMN firing properties are primarily due to age-dependent changes in the expression of voltage-sensitive calcium and calcium-activated potassium currents. 4) Both dye and electrical coupling have been detected amongst subpopulations of PMNs between ages E16 and P0. 5) There are marked changes in diaphragm muscle contractile properties that develop in concert with PMN repetitive firing properties so that the full-range of diaphragm force recruitment can be utilized at each age and potential problems of diaphragm fatigue are minimized. Data presented will be derived from the following references:

Highlights

  • To be effective, inspiratory muscles on the left and right sides must contract together

  • We have found that a prominent gap in the column of ventral respiratory group (VRG) The nucleus tractus solitarii (NTS) relays information from primary related parvalbumin cells [2] likely corresponds to the pBc since visceral receptors to the central nervous system and is critically parvalbumin cells are rare in this zone and never co-localize with involved in the reflex control of autonomic functions

  • The specific protein(s) necessary for longterm facilitation (LTF) is unknown, we recently found that episodic hypoxia and LTF are associated with elevations in ventral spinal concentrations of brain derived neurotrophic factor (BDNF)

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Summary

Introduction

Inspiratory muscles on the left and right sides must contract together. The left and right halves of the diaphragm are synchronised because a bilateral population of medullary premotor neurones [1] simultaneously excites left and right phrenic motoneurones. Transection studies demonstrate that each side of the brainstem is capable of generating respiratory rhythm independently [2], so that left and right medullary inspiratory neurones must themselves be synchronised. The interconnections and common excitation that accomplish such synchronisation are unknown in rats. The respiratory rhythm of hypoglossal (XII) nerve discharge in transverse medullary slice preparations from neonatal rats is thought to originate in the region of the ventral respiratory group (VRG); generated there by a combination of “pacemaker” neurones [1] and their interactions with other respiratory neurones. Our goal was to discover interconnections between left and right VRG neurones as well as their connections to XII motoneurones

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