The Effects Of Unilateral Conductive Hearing Loss On The Sound Localization And The Neural Tuning To Sound-source Azimuth In The Auditory Cortex Of Rats

Sound localization is ability of human and animals to identify the location of a detected sound in direction and distance.Accurate sound localization helps human and animals to perceive sound environment,separate and process the target sound from complex acoustic environment.Previous studies have shown that the accurate sound localization relies on the processing of sound information from the two ears by the auditory system.The binaural information includes interaural level difference and interaural time difference.In human,unilateral otitis media is a common hearing disease that causes temporal or chronic unilateral conductive hearing loss(UCHL);it induces abnormal binaural input and impairs the accurate sound localization.However,at present the neuronal and molecular mechanisms for the impacts of UCHL on the sound localization are not fully understood.The aims of the present study was to investigate how UCHL at different postnatal periods affects the sound localization ability of rats,and how UCHL affects the neural tuning to sound-source azimuth in the rat auditory cortex,and in addition,whether UCHL affects the density of neurons with the expression of AMPA receptor subunit GluR2 and parvalbumin positive neurons in the rat auditory cortex.Four groups of rats were used in the present study.The two UCHL groups of rats were the young unilateral conductive hearing loss group(YUCHL group)and the adult unilateral conductive hearing loss group(AUCHL group).We damaged the tympanic membrane and the malleus in the right ear from postnatal(P)14 for the YUCHL group of rats and from P57 for the AUCHL group of rats.After experienced two months UCHL,we used these rats do our designed experiments for the aims in the present study.The two control groups of rats,i.e.,the young control group(YCon group)and the adult control group(ACon group)of rats with normal binaural hearing,were the age-matched controls for the YUCHL group and for the AUCHL group,respectively.We used behavioral,neurophysiological,and immunohistochemistry techniques to do the experiments specific for the aims of the present study.The main results are as follows:1.Compared with the successful rate of sound localization performance in the two age-matched control groups,the ability of sound localization in the rats in both the YUCHL group and the AUCHL group was severely impaired,and the degree of this impairment was greater in the sound-source azimuths on the hearing loss ear side than those on the normal hearing ear side.On the side of hear loss ear,the success rate of sound localization performance for rats in both the YUCHL group and the AUCHL group was near the chance level,and showed no significant differences between the two UCHL groups.On the side of the intact ear,the success rate of sound localization performance was greater in the AUCHL group than in the YUCHL group.The results suggest that UCHL from early postnatal age induced a stronger impairment in sound localization ability than UCHL from adulthood did.These results were significant different from the findings in barn owls and ferrets showing adaptation to the abnormal binaural hearing conditions(i.e.,the animals can learn to use new sound localization cues in abnormal binaural hearing conditions to localize a sound).The results suggest that the phenomenon of adaptation to abnormal binaural hearing might not apply to all animals.2.We recorded the responses of the auditory cortex neurons to sound stimuli from the azimuths in the front auditory space of the four groups of rats.By analyzing the number of spikes and the first-spike latencies from the azimuth tuning curves of auditory cortical neurons,we compared the preferences to sound-source azimuth,the azimuth selectivity,and the azimuth sensitivity among the population of neurons in the four groups of rats.We found that the auditory cortex neuron in both the YCon group and the ACon group predominantly preferred the azimuth in the contralateral azimuths,and that no significant differences were found between the two control groups in the azimuth preference,the azimuth selectivity and the azimuth sensitivity.Compared with the data in the age-matched control group,in the auditory cortex contralateral to the hearing loss ear,UCHL induced a decrease in the percentage of neurons with contralateral azimuth preference(the azimuths on the hearing loss ear side)but an increase in the percentage of neurons with ipsilateral azimuth preference(the azimuths on the intact ear side),and this was more evident in YUCHL group than in the AUCHL group.UCHL also induced a significant decrease in azimuth selectivity and azimuth sensitivity of the auditory cortex neurons in both the YUCHL group and the AUCHL group,and this was more evident in the AUCHL group than in the YUCHL group.The average response latencies for the population of neurons in the two control groups were shorter in the contralateral azimuths than in the ipsilateral azimuths.In contrast,the average response latencies for neurons in the YUCHL group were shorter in the ipsilateral azimuths than in the contralateral azimuths.However,in the AUCHL group there were no significant differences in the average latencies between the contralateral azimuths and the ipsilateral azimuths.Our results demonstrated that UCHL significantly disrupted the normal tuning to source-source azimuth of rat auditory cortex neurons,and the degree of this impact was dependent on the postnatal time period of UCHL.3.Using immunohistochemistry technique,we determined the density of parvalbumin positive neurons and the density of neurons with the expression of AMPA receptor subunit GluR2 in the auditory cortex of the four groups of rats.The results show that,compared with the data in age-mated control group,UCHL did not significantly change the density of parvalbumin positive neurons in the auditory cortex of rats in both YUCHL group and AUCHL group;in addition,UCHL did not significantly change the density of neurons with the expression of AMPA receptor subunit GluR2 in the auditory cortex of rats in both YUCHL group and AUCHL group.To our knowledge,the present study is the first demonstration of how chronic unilateral hearing loss at different postnatal ages affects the azimuth tuning of AI neurons in the free-field acoustic stimulus conditions.The results provide a possible neural mechanism for the impacts of UCHL during different postnatal periods on the sound localization performance,and also provide experimental evidences for us to understand the mechanism of the impacts of UCHL(induced by otitis media or other factors)on the function of the auditory system.