National Institute on Deafness and Other Communication Disorders (NIDCD) 5R01DC021671-03

Top-down modulation of the dorsal cochlear nucleus

This project investigates how top-down signals from the inferior colliculus modulate auditory processing in the dorsal cochlear nucleus to improve hearing accuracy, using advanced neural circuit and electrophysiological methods in mice. The findings aim to enhance understanding of auditory perception and potential treatments for hearing loss and auditory disorders.

Description

An animal’s survival depends on their accurate perception of biologically relevant sounds in a complex hearing environment that is awash with background noise. Top-down contextual information modulates the processing of bottom-up sensory signals at multiple levels of the auditory pathway to improve hearing accuracy, but the neural mechanisms underlying this essential function remain unclear, especially at the earliest processing level in central auditory system. Here we examine the role of the massive top-down projection from the inferior colliculus (IC) to the dorsal cochlear nucleus (DCN). Our overarching hypothesis is that top-down signals that encode contextual information are conveyed to DCN by descending IC projections to guide context-dependent filtering. The proposed project will reveal the circuit mechanisms of top-down modulation at the first level of auditory processing in the central nervous system. This work could provide insight into ways to improve auditory perception when bottom-up signals are degraded due to hearing loss, as well as auditory processing disorders for which top-down modulation has been implicated. Early filtering that is guided by top-down modulation is a general principle in sensory systems. Establishing how neural circuits implement context-dependent filtering has been difficult, due in part to a lack of in vivo phenomenological studies being combined with circuit-level analysis. We will examine the neural mechanisms underlying top-down modulation of the DCN by utilizing a powerful combination of (1) neural circuit analysis using projection-specific retrograde tracing, (2) in vitro acute brain slice electrophysiology in transgenic mice, and (3) cutting-edge in vivo electrophysiology and optogenetics in awake mice. Research Aims: Aim 1: Test if DCN-projecting IC neurons are a subtype of small cells in the central nucleus. Aim 2: Investigate how descending IC projections are processed by specific cells and microcircuits in DCN. Aim 3: Examine how descending IC projections shape auditory responses of DCN principal neurons in awake mice. Impact: Successful completion will establish how top-down projections from IC modulate auditory responses in the first level of auditory processing and reveal circuit mechanisms contributing to accurate auditory processing in complex sound environments.

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