부산대학교 도서관

Sound localization relies on minute differences in the timing and intensity of sound arriving at both ears. Neurons of the lateral superior olive (LSO) in the brainstem process these interaural disparities by precisely detecting excitatory and inhibitory synaptic inputs. Aging generally induces selective loss of inhibitory synaptic transmission along the entire auditory pathways, including the reduction of inhibitory afferents to LSO. Electrophysiological recordings in animals, however, reported only minor functional changes in aged LSO. The perplexing discrepancy between anatomical and physiological observations suggests a role for activity-dependent plasticity that would help neurons retain their binaural tuning function despite loss of inhibitory inputs. To explore this hypothesis, we use a computational model of LSO to investigate mechanisms underlying the observed functional robustness against age-related loss of inhibitory inputs. The LSO model is an integrate-and-fire type enhanced with a small amount of low-voltage activated potassium conductance and driven with (in)homogeneous Poissonian inputs. Without synaptic input loss, model spike rates varied smoothly with interaural time and level differences, replicating empirical tuning properties of LSO. By reducing the number of inhibitory afferents to mimic age-related loss of inhibition, overall spike rates increased, which negatively impacted binaural tuning performance, measured as modulation depth and neuronal discriminability. To simulate a recovery process compensating for the loss of inhibitory fibers, the strength of remaining inhibitory inputs was increased. By this modification, effects of inhibition loss on binaural tuning were considerably weakened, leading to an improvement of functional performance. These neuron-level observations were further confirmed by population modeling, in which binaural tuning properties of multiple LSO neurons were varied according to empirical measurements. These results demonstrate the plausibility that homeostatic plasticity could effectively counteract known age-dependent loss of inhibitory fibers in LSO and suggest that behavioral degradation of sound localization might originate from changes occurring more centrally. Author summary: Accurately locating a sound source is one of the most fundamental functions of the auditory system. Behavioral studies report that sound localization ability generally degrades with aging in both laboratory animals and humans. Anatomical studies in aged animals have observed considerable reductions of inhibitory inputs into the neuronal circuit responsible for sound localization. Paradoxically, physiological studies at the brainstem level, however, find only minor age-related changes in the function of the sound localization circuit. In order to bridge the puzzling discrepancy between these observations, we developed a model of the corresponding neuronal circuit and simulate its function by varying the number of inhibitory afferents. To simply mimic the activity-dependent adjustment of synaptic inputs, we also varied the strength of remaining inhibition. Consistent with the empirical findings, our simulations demonstrate that functional changes of the sound localization circuit remain relatively small, compared to the reduced number of inhibitory inputs. This functional robustness is further enhanced by adjusting the synaptic strength. These results suggest that the age-related degradation of sound localization behavior might be caused by altered functions of higher stages in the auditory pathways above the level of the brainstem. [ABSTRACT FROM AUTHOR]