Psychophysical and neural correlates of noised-induced tinnitus in animals: Intra- and inter-auditory and non-auditory brain structure studies

•Our new operant behavior paradigm produces fast and reliable testing for tinnitus.•Tinnitus involves both auditory and non-auditory brain structures.•Hyper-activity and synchrony in the AC and AMG contributes to tinnitus percepts.•Hypersynchrony between the AC and AMG mediates tinnitus percepts.

Tinnitus, a ringing in the ear or head without an external sound source, is a prevalent health problem. It is often associated with a number of limbic-associated disorders such as anxiety, sleep disturbance, and emotional distress. Thus, to investigate tinnitus, it is important to consider both auditory and non-auditory brain structures. This paper summarizes the psychophysical, immunocytochemical and electrophysiological evidence found in rats or hamsters with behavioral evidence of tinnitus. Behaviorally, we tested for tinnitus using a conditioned suppression/avoidance paradigm, gap detection acoustic reflex behavioral paradigm, and our newly developed conditioned licking suppression paradigm. Our new tinnitus behavioral paradigm requires relatively short baseline training, examines frequency specification of tinnitus perception, and achieves sensitive tinnitus testing at an individual level. To test for tinnitus-related anxiety and cognitive impairment, we used the elevated plus maze and Morris water maze. Our results showed that not all animals with tinnitus demonstrate anxiety and cognitive impairment. Immunocytochemically, we found that animals with tinnitus manifested increased Fos-like immunoreactivity (FLI) in both auditory and non-auditory structures. The manner in which FLI appeared suggests that lower brainstem structures may be involved in acute tinnitus whereas the midbrain and cortex are involved in more chronic tinnitus. Meanwhile, animals with tinnitus also manifested increased FLI in non-auditory brain structures that are involved in autonomic reactions, stress, arousal and attention. Electrophysiologically, we found that rats with tinnitus developed increased spontaneous firing in the auditory cortex (AC) and amygdala (AMG), as well as intra- and inter-AC and AMG neurosynchrony, which demonstrate that tinnitus may be actively produced and maintained by the interactions between the AC and AMG.