Central respiratory neuronal activity after axonal regeneration within blind-ended peripheral nerve grafts: time course of recovery and loss of functional neurons

Abstract

Autologous segments of peroneal nerve were implanted into the medulla of adult rats to induce axonal regeneration of central neurons axotomised during the grafting procedure. Grafts were inserted in the midline where respiratory axons decussate or laterally, either in the nucleus tractus solitarius or in the nucleus ambiguus, close to respiratory cell bodies. The distal part of each graft was left unconnected (blind-ended graft). Between 2 and 30 months post-implantation, unit recordings from single fibres were made from small strands teased from the grafts to investigate activity of neurons regenerating axons. Spontaneous respiratory and non-respiratory activity was present only in grafts examined between 2 and 6 months post-implantation. Respiratory units had discharge patterns identical to those of normal inspiratory or expiratory neurons; their responses to lung inflation and asphyxia were also similar to those of central respiratory neurons. No spontaneous activity was present in the grafts examined 7–30 months post-implantation. Moreover, asphyxia, which normally enhances the activity of central respiratory neurons, failed to elicit activity. These results were similar in all grafts, regardless of the site of implantation. The presence of spontaneous activity only between 2 and 6 months post-implantation indicates that once axonal growth of respiratory neurons is stopped within blind-ended grafts, those neurons still exhibited normal functional properties for 3 months. The absence of activity 6 months after grafting suggests that loss of functional regenerating respiratory neurons does not occur progressively and follows an “all or nothing” rule within blind-ended grafts.