Title

Plasticity of synaptic endings in the cochlear nucleus following noise-induced hearing loss is facilitated in the fibroblast growth factor 2 overexpressor mouse

Date of Completion

January 2006

Keywords

Health Sciences, Audiology|Biology, Neuroscience

Degree

Ph.D.

Abstract

In adult mammals a single exposure to loud noise can damage cochlear hair cells and cause axonal degeneration in the cochlear nucleus. The possible mechanisms for the axonal and synaptic degeneration in the cochlear nucleus could be loss of trophic support and/or excitotoxicity. Fibroblast growth factor 2 (FGF2), which is important for neurite outgrowth and synapse formation during the development of the cochlear nucleus and the spiral ganglion, might be involved in either mechanism. To test this hypothesis we noise-exposed FGF2 overexpressor mice, which have an excess of FGF2 and wild-type controls to observe the effects on synaptic endings by immunolabeling a pre-synaptic marker, synaptic vesicular protein 2 (SV2). SV2 staining was observed in two major locations: perisomatic, representing axo-somatic terminals, and neuropil, representing axo-dendritic terminals. In the overexpressor, the perisomatic clusters remained unchanged after an intervening period of increase. The neuropil clusters underwent an initial decline, followed by a transient recovery and ultimate decline. On the other hand, the wild-type lost both the perisomatic and neuropil clusters, with an intervening period of modest recovery for the perisomatic clusters. ^ Previous work has shown that in the cochlear nucleus large perisomatic clusters mostly represent excitatory cochlear nerve endings, while neuropil clusters include inhibitory endings. Thus the overexpressor preserves excitatory perisomatic cochlear nerve endings and promotes recovery of neuropil clusters, including presumptive inhibitory synapses from interneurons. This raises the question of whether there was a change in the numbers of excitatory vs. inhibitory synapses. Hence we studied the inhibitory and excitatory receptors in the wild-type and overexpressor after noise. In the wild-type and overexpressor, GABA Aα1 staining increased at the soma by 2 weeks and stayed elevated for 4 weeks. In contrast, the staining for NMDAR1 and R2A decreased at 2 weeks and returned to control level by 4 weeks. The findings that GABA Aα1 increased, while the NMDA receptors decreased, suggest that there is a shift to inhibition in the wild-type, but not necessarily in the overexpressor where the receptor changes were not accompanied by SV2 loss.^