Mechanisms for cancelling self-generated sounds in the mouse dorsal cochlear nucleus

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Project Summary/Abstract Our own movements result in patterns of sensory receptor activation that may be similar or identical to those caused by external events. How does the brain make the critical distinction between self and other? Longstanding theories suggest that proprioceptive feedback or internal copies of motor commands, known as corollary discharge, could serve to predict and cancel out sensory input due to an animal’s own movements. However, it has been difficult to understand where and how such a process actually takes place within the brain. Some of the clearest insights come from cerebellum-like sensory structures associated with electrosensory processing in fish. Work in these systems, including that of the PI, has shown that synaptic plasticity acting on motor corollary discharge and proprioceptive information functions to predict and cancel out self-generated electrosensory inputs related to the fish’s own behavior. This proposal seeks to understand whether similar mechanisms are at work in the mammalian brain. Specifically, we focus on the dorsal cochlear nucleus (DCN)--a structure at the initial stage of mammalian auditory processing which strikingly resembles cerebellum-like structures in fish in terms of its circuitry and synaptic plasticity rules. We will use in vivo recordings from awake, behaving mice to test whether non-auditory, movement-related input to DCN functions to predict and cancel self-generated sounds associated with licking behavior. The proposed research is expected to provide fundamental insight into the computations performed by the DCN, including an answer to the longstanding question of why circuitry at the first stage of mammalian auditory processing resembles that of the cerebellum. More generally, this work will provide mechanistic insights into how the mammalian brain distinguishes between self-generated and external sources of sensory input. Finally, the common and in some cases debilitating condition of tinnitus—the persistent perception of sound in the absence of an external sound source—is associated with hyperactivity in DCN neurons and is hypothesized to be due, in part, to aberrant synaptic plasticity and somatosensory integration in DCN. This project seeks to understand the normal function of synaptic plasticity and somatosensory integration in DCN and hence may also provide insights into the pathophysiology of tinnitus.