Distribution of Glutamatergic and Glycinergic Inputs onto Human Auditory Coincidence Detector Neurons

Abstract

Localization of sound sources in the environment requires neurons that extract interaural timing differences (ITD) in low-frequency hearing animals from fast and precisely timed converging inputs from both ears. In mammals, this is accomplished by neurons in the medial superior olive (MSO). MSO neurons receive converging excitatory input from both the ipsilateral and contralateral cochlear nuclei and glycinergic, inhibitory input by way of interneurons in the medial and lateral nuclei of the trapezoid body (MNTB and LNTB, respectively). Key features of the ITD circuit are MSO neurons with symmetric dendrites that segregate inputs from the ipsilateral and contralateral ears and preferential distribution of glycinergic inputs on MSO cell bodies. This circuit for ITD is well characterized in gerbils, a mammal with a prominent MSO and a low-frequency hearing range similar to humans. However, the organization of this circuit in the human MSO has not been characterized. This is further complicated by limited understanding of the human LNTB. Nonetheless, we hypothesized that the ITD circuit characterized in laboratory animals is similarly arranged in the human MSO. Herein, we utilized neuron reconstructions and immunohistochemistry to investigate the distribution of glutamatergic and glycinergic inputs onto human MSO neurons. Our results indicate that human MSO neurons have simple, symmetric dendrites and that glycinergic inputs outnumber glutamatergic inputs on MSO cell bodies and proximal dendrites. Together these results suggest that the human MSO utilizes similar circuitry to other mammals with excellent low-frequency hearing.