Cochlear damage induces GAP-43 expression in cholinergic synapses of the cochlear nucleus in the adult rat: a light and electron microscopic study.
Recent studies suggest a potential for activity-dependent reconstruction in the adult mammalian brainstem that exceeds previous expectations. We found that a unilateral cochlear lesion led within 1 week to a rise of choline acetyltransferase (ChAT) immunoreactivity in the ventral cochlear nucleus of the affected side, matching the lesion-induced expression of growth-associated protein 43 (GAP-43) previously described. The rise of both ChAT and GAP-43 immunoreactivity was reflected in the average density of the staining. Moreover, the number of light-microscopically identifiable boutons increased in both stains. GAP-43-positive boutons could, by distinct ultrastructural features, regularly be identified as presynaptic endings. However, GAP-43 immunoreactivity was not only found in presynaptic endings with a classical morphology, but also in profiles that suggest morphological dynamic structures by showing filopodia, assemblages of pleomorphic vesicles, large vesicles (diameter up to 200 nm) fusing with the presynaptic plasma membrane close to synaptic contacts, small dense-core vesicles (diameter about 80 nm) and presynaptic ribosomes. Moreover, we observed perforated synapses as well as GAP-43 immunoreactivity condensed in rafts, both indicative of growing or changing neuronal connections. Classical and untypical ultrastructural profiles that contained GAP-43 also contained ChAT. We conclude that there is extensive deafness-induced GAP-43-mediated synaptic plasticity in the cochlear nucleus, and that this plasticity is predominantly, if not exclusively, based on cholinergic afferents.
Meidinger
Markus A
MA
Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, D-79106 Freiburg, Germany.
Hildebrandt-Schoenfeld
Heika
H
Illing
Robert-Benjamin
RB
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003051:Cochlea / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D017626:Cochlear Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D019922:GAP-43 Protein / Q000378:metabolism*; D007150:Immunohistochemistry; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
D019922:GAP-43 Protein; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine