The environment is constantly changing around us, to provide accurate information upon which to base decisions and actions, the brain must be flexible and adapt to these rapidly changing surroundings. To deal with these changes, neurons can adapt their sensitivity or tuning to represent the most important aspects of the environment. Sound location is a fundamental aspect of understanding the auditory environment and is important for survival, after all one wants to run away from danger, not towards it. Neurons in the brain can adapt to sound location and sound location perception of humans can be altered by spatial adaptors1. However, the mechanisms underlying neuronal adaptive coding and how it directly alters auditory spatial perception remain unknown. We aim to perform simultaneous neuronal activity recordings and sound location perception testing in the presence of adapting stimuli to investigate the mechanism of spatial adaptation and the effects of adaptation on auditory spatial perception.
To study how adaptation to sound location affects perception we first designed a behavioural task to probe sound location perception in mice. Given the size of the mouse head, it is most likely that mice rely on interaural level difference to localize sounds in the horizontal plane2. Subsequently, head-fixed mice were trained in a lateralization task where they reported the location (left/right) of a sound based on the interaural level difference. There is a large body of work to suggest that the auditory cortex is necessary for sound localization ability3, however, this has not been tested in mice. Furthermore, it has been shown that feedback from the auditory cortex (AC) to the inferior colliculus (IC) affects spatial tuning properties of neurons in the IC4 and is necessary for adaptation to unilateral hearing loss5. To test the role of AC in sound location perception, we used optogenetics to modulate activity of AC or cortico-collicular feedback neurons during task performance.
We found that mice were able to perform the task, with 5/6 mice successfully completing training and testing. Sensitivity to sound location was assessed by finding the slope of a logistic regression fitted to the psychometric curves of mice with and without optogenetic manipulation. Inactivation of excitatory neurons in the auditory cortex during task performance reduced sensitivity to sound location (n = 2 mice), while neither inactivation (n = 2 mice) nor activation (n = 2 mice) of cortico-collicular feedback neurons during task performance affected sensitivity to sound location.
Mice successfully learned to report the location of a sound based on the interaural level difference. Preliminary results indicate that inactivation of excitatory activity in the auditory cortex affected task performance and reduced sensitivity of mice to sound location. Modulation of cortico-collicular feedback did not affect task performance or the sound location sensitivity of the mice. In future work mice will be required to perform the task in the presence of a spatial adaptor sound.
All experimental procedures were in accordance with NIH guidelines and approved by the IACUC at the University of Pennsylvania.