Effects of Acoustic Trauma on the Induction of Long-term Potentiation in the Inferior Colliculus of Rats

Tinnitus is an auditory disorder that is commonly classified as a ringing in the ears without an external sound source. Tinnitus is mainly correlated with increased age, however, noise exposure to loud sounds is also considered a main risk factor for tinnitus. It is hypothesized that tinnitus may arise from hyperactivity in neurons within key brain regions of the auditory pathway, such as the inferior colliculus. The hyperactivity of neurons in the inferior colliculus has been linked with decreased GABA activity in tinnitus animals. Additionally, decreased GABA inhibition of these neurons also leads to long-term potentiation (LTP) in the inferior colliculus. The aim of this project is to compare the induction of LTP in the inferior colliculus between normal rats and rats exposed to intense acoustic trauma. Initially, a method of LTP induction was developed in the inferior colliculus of normal rats. Results showed that rats treated with the GABA-A receptor antagonist picrotoxin (2.5 mg/kg, s.c.) and tetanic stimulation (50 Hz, 20 s) had significantly elevated response amplitudes (P = 0.0001) in comparison to rats that were treated with picrotoxin only or tetanic stimulation only. The elevated responses were maintained throughout the 2 h period, which demonstrates induction of LTP. This suggests that LTP can only be induced in normal animals when GABA transmission is inhibited. In a separate experiment, rats were exposed to acoustic trauma (a 16 kHz, 130 dB pure tone presented unilaterally for 1 h) and were tested for behavioural evidence of tinnitus using a conditioned lick-suppression paradigm. A significant increase in the auditory brainstem-evoked response thresholds of acoustic trauma-exposed animals (P = 0.0001) confirmed hearing loss after acoustic trauma. There were no reliable signs of tinnitus behaviour in the exposed animals in the tinnitus assessment that followed acoustic trauma. However, when the animals were subjected to tetanic stimulation only without the use of picrotoxin, exposed animals exhibited a statistically significant increase in the evoked potentials over time (P = 0.0001) in comparison to the control animals. These results demonstrated for the first time that LTP induction is facilitated in the inferior colliculus of rats at 5 months after acoustic trauma, which suggests that acoustic trauma may cause long-term pathological changes that lead to loss of inhibition similar to what observed following the inhibition of GABA-A receptors. Future studies are needed to understand the mechanisms of LTP facilitation following acoustic trauma and explore the role of LTP in acoustic trauma-induced tinnitus