The dorsal cochlear nucleus (DCN) contains a cerebellum-like circuit in the first stage of auditory processing. Fusiform cells (FCs) integrate primary auditory information conveyed via the auditory nerve with information conveyed via mossy fiber-granule cell-parallel fiber system. Cartwheel cells (CWCs), a major inhibitory interneuron in the DCN also receiving parallel fiber input, closely resembles Purkinje cells in morphology, physiology, and pattern of gene expression. Mossy fiber input to DCN convey a range of non-auditory information including information from the spinal-trigeminal nucleus, the cuneate nucleus, the vestibular nucleus, the lateral reticular nucleus, and the pons. Aberrant plasticity in FCs has been implicated in tinnitus, the perception of a sound without the existence of an external sound source. Patients who have tinnitus have reported being able to modulate the amplitude and frequency of the perceived sound through movement of the jaw and neck demonstrating the multisensory integration involved in this pathology. Why such sensory integration occurs at so early a stage in auditory processing has long puzzled scientists. One prevailing hypothesis comes from evidence from a similar cerebellum-like structure involved in electrosensory processing in weakly electric fish, the electrosensory lateral lobe (ELL). Signals conveyed via its mossy fiber-granule cell-parallel fiber system are used as predictive signals to cancel electrosensory information generated by the fish's own behavior to better process behaviorally relevant stimuli from the environment. These predictions are generated by anti-Hebbian plasticity rules at parallel fiber synapses onto ELL efferent cells. Similar plasticity ruls are found at parallel fiber synapses in DCN. This proposal will test if the DCN performs a similar function, namely the prediction and cancellation of self-generated sensory stimuli. The first goal of this proposal is to first characterize DCN responses to non-auditory input, namely outer ear (pinna) movement in both anesthetized and awake mice. While there have been anatomical and electrophysiologic studies in a number of species including cats, guinea pigs, and rats, little is known about non-auditory input to DCN in mice. I will then test the hypothesis that these inputs are used as predictive signals to separate behaviorally relevant from self-generated sensory stimuli. These studies will provide the first insights into the function of the DCN and allow futur studies to use the powerful genetic and molecular techniques developed for mice to further study the roles of a cerebellum-like circuit in sensory processing.
Hyperactivity in fusiform cells of the dorsal cochlear nucleus has been implicated in tinnitus, the perception of sound in the absence of an external sound source. Plasticity of somatosensory inputs to DCN causing this hyperactivity is a leading hypothesis. This proposal will provide insights to the role of normal plasticity in DCN and may ultimately lead to possible treatments for tinnitus.
|Singla, Shobhit; Dempsey, Conor; Warren, Richard et al. (2017) A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds. Nat Neurosci 20:943-950|