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For successful future therapeutic strategies for tinnitus and hyperacusis, a subcategorization of both conditions on the basis of differentiated neural correlates would be of invaluable advantage. In the present study, we used our refined operant conditioning animal model to divide equally noise-exposed rats into groups with either tinnitus or hyperacusis, with neither condition, or with both conditions co-occurring simultaneously. Using click stimulus and noise burst-evoked Auditory Brainstem Responses (ABR) and Distortion Product Otoacoustic Emissions, no hearing threshold difference was observed between any of the groups. However, animals with neither tinnitus nor hyperacusis responded to noise trauma with shortened ABR wave I and IV latencies and elevated central neuronal gain (increased ABR wave IV/I amplitude ratio), which was previously assumed in most of the literature to be a neural correlate for tinnitus. In contrast, animals with tinnitus had reduced neural response gain and delayed ABR wave I and IV latencies, while animals with hyperacusis showed none of these changes. Preliminary studies, aimed at establishing comparable non-invasive objective tools for identifying tinnitus in humans and animals, confirmed reduced central gain and delayed response latency in human and animals. Moreover, the first ever resting state functional Magnetic Resonance Imaging (rs-fMRI) analyses comparing humans and rats with and without tinnitus showed reduced rs-fMRI activities in the auditory cortex in both patients and animals with tinnitus. These findings encourage further efforts to establish non-invasive diagnostic tools that can be used in humans and animals alike and give hope for differentiated classification of tinnitus and hyperacusis., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Synaptosomes isolated from the rat brain corpus striatum and locust head and thoracic ganglia were loaded with radioactive neurotransmitter ([3H]dopamine and [3H]acetylcholine, respectively) and then treated with alpha-latrotoxin and other fractions (fractions C, D and E of Frontali et al.8) obtained by Sephadex G200 column chromatography from black widow spider venom gland homogenates. As shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, alpha-latrotoxin is a high Mr protein, whereas fractions C-E are mixtures of several proteins, that include small amounts of contaminating alpha-latrotoxin (especially in fraction C). In rat synaptosomes alpha-latrotoxin induced massive neurotransmitter release, and some release was induced also by high concentrations of fractions C and D. These responses were blocked almost completely by a monospecific anti-alpha-latrotoxin serum, indicating that they were all due to alpha-latrotoxin. Release of [3H]acetylcholine from locust synaptosomes was induced by the various preparations investigated. alpha-Latrotoxin was about 10-fold less potent in locust than in rat synaptosomes. The effects of fractions C-E tended to disappear with storage. The most active batches of fractions C and E were even more potent than alpha-latrotoxin, while the D fraction was approximately 5-fold less potent. The anti-alpha-latrotoxin antiserum inhibited part of the responses elicited by fractions C and E, but left fraction D almost unaffected. Release by D and E fractions was maintained even when Ca2+ was removed from the incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS)