Neuronal precision, accuracy, and fidelity: inhibitory and excitatory inputs to the lateral superior olive

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Ultrafast signaling and exquisitely high temporal precision down to the microsecond range are hallmarks of the auditory system that set it apart from virtually any other sensory system. Neurons in the lateral superior olive (LSO), a key brainstem nucleus, compare excitatory (glutamatergic) and inhibitory (glycinergic) inputs from the ipsilateral and contralateral ear, respectively. LSO neurons are thus sensitive to inter-aural level differences, one of the primary cues in sound localization. To fulfill the task of sound localization, fast, precise, and sustained synaptic transmission is thought to be crucial. Glycinergic input neurons to the LSO fire action potentials reliably at frequencies up to 800 Hz. It is unclear whether these features are faithfully processed onto LSO neurons and how precisely and reliably they are integrated with glutamatergic inputs. To address this important issue, we propose to analyze the precision, accuracy, and fidelity of both types of LSO inputs and to reveal some of the underlying mechanisms. Electrophysiological recordings will be obtained in mouse brain slices while activating the inputs electrically at various frequencies and durations. Characterization will comprise recordings in wild-type and appropriate knock-out mice. Our results will help to understand how fine tuning of auditory synapses for speed, precision, and fidelity is obtained in excitatory and inhibitory inputs. As abnormalities in the auditory brainstem may be related to problems in sound processing and speech recognition, we hope to contribute to a better diagnosis of central auditory processing disorders.