Synaptic Remodeling in the Vagal Nuclei Following Vagal-hypoglossal Nerve Anastomosis

Synaptic remodeling associated with neuronal and glial changes in the vagal dorsal motor nucleus (DMV) and nucleus ambiguous (NA) after vagal-hypoglossal nerve anastomosis (VHA). At 25 days postoperation (dpo), there were 50% fewer presynaptic boutons containing round vesicles (R) or round and large dense-cored synaptic vesicles (R+D) contacting HRP-labeled DMV motoneurons. The loss of R boutons was maintained throughout the remaining postoperative intervals up to 500 dpo, whereas R+D boutons were further reduced at 123 dpo but were restored at 315 dpo so that by 500 dpo, 71.4% of them had gained access to the DMV motoneurons. Boutons containing pleomorphic synaptic vesicles (P) were completely disconnected from the DMV motoneurons at 25 dpo and did not reappear even in long-term reinnervation stage. Loss and recovery of presynaptic boutons occurred in parallel with changes in astroglial ensheathment of the DMV motoneurons. However, the vagal efferent neurons in the NA had responded to VHA in a different manner. Firstly, the numbers of R, R+D, P or F (containing flattened synaptic vesicles) boutons contacting the NA motoneurons were markedly increased at 500 dpo. Secondly, the astroglial ensheathment was not evident in the NA. Thirdly, the extensive dendritic sprouting of the NA neurons as opposed to the dendritic retraction of the DMV neurons. The differences between NA and DMV may be attributed to the unique nature of the two nuclei to structures they normally supply and their different compatibility with the newly innervated target, viz. tongue skeletal musculature. INTRODUCTION Experiments using vagal-hypoglossal nerve anastomosis (VHA) have been carried out in rats by Flumerfelt et al. (1986) [8] and McWilliam et al. (1995) [33] and, more recently, in cats by us [5, 27, 28]. These studies [8, 33] had demonstrated that after VHA, the general visceral efferent (GVE) neurons in the dorsal motor nucleus of the vagus (DMV) can reinnervate the tongue musculature by sending their axon terminals to motor endplates initially occupied by the hypoglossal nerve [8]. Neuronal phenotype in the DMV was also altered from CGRP-negative to CGRP-positive [33]. Our study had extended this to show that in long-term VHA, the GVE neurons in the DMV exhibited signs of dendritic withdrawal and that they were ensheathed by hypertrophied astroglial processes [27, 28]. In light of the above, we suggested that the autonomic nature of the DMV motoneurons was not appropriate for the newly acquired target, viz. the tongue skeletal musculature, for voluntary movement and, hence, some chemical [33] and structural [5, 27, 28] modifications would be necessary for the regenerating DMV motoneurons to facilitate a better functional recovery after VHA. Furthermore, with the astroglial ensheathment induced by VHA, the regenerating DMV motoneurons could physically displace most, if not all, of the synaptic boutons related to autonomic function [27]. Our experimental results furthermore suggested that neural plastic changes in the DMV may be influenced by some retrogradely transported factors/signals derived from the new target organ, tongue muscles [27]. This view is