Synaptic Reorganization in the Adult Rat's Ventral Cochlear Nucleus following Its Total Sensory Deafferentation

Ablation of a cochlea causes total sensory deafferentation of the cochlear nucleus in the brainstem, providing a model to investigate nervous degeneration and formation of new synaptic contacts in the adult brain. In a quantitative electron microscopical study on the plasticity of the central auditory system of the Wistar rat, we first determined what fraction of the total number of synaptic contact zones (SCZs) in the anteroventral cochlear nucleus (AVCN) is attributable to primary sensory innervation and how many synapses remain after total unilateral cochlear ablation. Second, we attempted to identify the potential for a deafferentation-dependent synaptogenesis. SCZs were ultrastructurally identified before and after deafferentation in tissue treated for ethanolic phosphotungstic acid (EPTA) staining. This was combined with pre-embedding immunocytochemistry for gephyrin identifying inhibitory SCZs, the growth-associated protein GAP-43, glutamate, and choline acetyltransferase. A stereological analysis of EPTA stained sections revealed 1.11±0.09 (S.E.M.)×109 SCZs per mm3 of AVCN tissue. Within 7 days of deafferentation, this number was down by 46%. Excitatory and inhibitory synapses were differentially affected on the side of deafferentation. Excitatory synapses were quickly reduced and then began to increase in number again, necessarily being complemented from sources other than cochlear neurons, while inhibitory synapses were reduced more slowly and continuously. The result was a transient rise of the relative fraction of inhibitory synapses with a decline below original levels thereafter. Synaptogenesis was inferred by the emergence of morphologically immature SCZs that were consistently associated with GAP-43 immunoreactivity. SCZs of this type were estimated to make up a fraction of close to 30% of the total synaptic population present by ten weeks after sensory deafferentation. In conclusion, there appears to be a substantial potential for network reorganization and synaptogenesis in the auditory brainstem after loss of hearing, even in the adult brain

Evidence of Key Tinnitus-Related Brain Regions Documented by a Unique Combination of Manganese-Enhanced MRI and Acoustic Startle Reflex Testing

Animal models continue to improve our understanding of tinnitus pathogenesis and aid in development of new treatments. However, there are no diagnostic biomarkers for tinnitus-related pathophysiology for use in awake, freely moving animals. To address this disparity, two complementary methods were combined to examine reliable tinnitus models (rats repeatedly administered salicylate or exposed to a single noise event): inhibition of acoustic startle and manganese-enhanced MRI. Salicylate-induced tinnitus resulted in wide spread supernormal manganese uptake compared to noise-induced tinnitus. Neither model demonstrated significant differences in the auditory cortex. Only in the dorsal cortex of the inferior colliculus (DCIC) did both models exhibit supernormal uptake. Therefore, abnormal membrane depolarization in the DCIC appears to be important in tinnitus-mediated activity. Our results provide the foundation for future studies correlating the severity and longevity of tinnitus with hearing loss and neuronal activity in specific brain regions and tools for evaluating treatment efficacy across paradigms

On the Role of the Wideband Inhibitor in the Dorsal Cochlear Nucleus: A Computational Modeling Study

Principal cells (type IV units) in the dorsal cochlear nucleus (DCN) are uniquely sensitive to (are inhibited by) energy minima or notches in acoustic spectra, which provide cues to sound localization. The once accepted conceptual model of the DCN suggested that this sensitivity was shaped largely by inhibitory inputs from wideband inhibitors (WBIs), which received auditory nerve inputs over a wide frequency range and inhibited type IV units over a narrow frequency range. A computational model based on this wide-input narrow-output conceptual model was able to reproduce quantitatively type IV unit responses to notch-noise stimuli as a function of notch width. Recent physiological results have shown however that WBIs are unresponsive to notch-noise stimuli with wide notch widths and thus have narrower auditory nerve fiber input bandwidths than previously assumed. A computational model based on a narrow-input narrow-output model of the WBI was unable to account fully for the notch sensitivity of type IV units suggesting the need to add a new component to the DCN circuit. The goal of this study was to test whether making the output bandwidth of the WBIs wide while keeping their input bandwidth narrow could explain the responses of type IV units to notch-noise stimuli. Anatomical evidence supports this model configuration, and the results show that such a model can produce strong inhibition in type IV units for wide notches. The results thus suggest that WBIs, in narrow-input wide-output form, are sufficient to account for the notch sensitivity of DCN type IV units

Diagnosis of osteoporotic vertebral fractures in children

Osteoporosis is a generalised disorder of the skeleton with reduced bone density and abnormal bone architecture. It increases bone fragility and renders the individual susceptible to fractures. Fractures of the vertebrae are common osteoporotic fractures. Vertebral fractures may result in scoliosis or kyphosis and, because they may be clinically silent, it is imperative that vertebral fractures are diagnosed in children accurately and at an early stage, so the necessary medical care can be implemented. Traditionally, diagnosis of osteoporotic vertebral fractures has been from lateral spine radiographs; however, a small number of studies have shown that dual energy x-ray absorptiometry is comparable to radiographs for identifying vertebral fractures in children, while allowing reduced radiation exposure. The diagnosis of vertebral fractures from dual energy x-ray absorptiometry is termed vertebral fracture assessment. Existing scoring systems for vertebral fracture assessment in adults have been assessed for use in children, but there is no standardisation and observer reliability is variable. This literature review suggests the need for a semiautomated tool that (compared to the subjective and semiquantitative methods available) will allow more reliable and precise detection of vertebral fractures in children