# Corticofugal Circuits for Active Listening

> **NIH NIH R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2020 · $442,298

## Abstract

Project Summary
During active listening, sound features that are distracting, irrelevant, or totally predictable are suppressed and
do not rise to perceptual awareness. By contrast, inputs selected for amplification convey behaviorally relevant
auditory signals used to guide ongoing perceptual decision making. The neural circuit mechanisms that
selectively suppress or amplify bottom-up inputs to support active listening remain largely mysterious.
Logically, neurons that support active listening would have inputs from cognitive signals that encode
expectation, attentional selection and task demands, yet would also be able to adjust the gain and tuning of
low-level auditory neurons that encode or compute bottom-up sound features. The massive network of
descending auditory corticofugal neurons fit the bill because their cell bodies are embedded in highly plastic
centers for cortical sound processing, yet their axons innervate subcortical auditory nuclei in the thalamus,
midbrain and brainstem. Addressing the involvement of corticofugal neurons in active listening behaviors has
been challenging due to the technical difficulty of isolating and manipulating specific classes of auditory cortex
neurons in awake, actively listening animals. Here, we describe an approach to overcome these technical
obstacles and address the hypothesis that a specific sub-class of auditory corticofugal neuron, the layer 6
corticothalamic neuron (L6 CT), plays an essential role in sculpting enhanced cortical and perceptual
processing of expected sounds. In Aim 1, we will use cutting-edge methods for cell type-specific imaging and
electrophysiology in awake, behaving mice to make targeted recordings from two classes of auditory
subcerebral projection neurons: layer 5 corticocollicular neurons (L5 CCol) and L6 CTs. We expect to find stark
differences in the auditory tuning, sensitivity to internal state variables, local outputs and monosynaptic inputs
of L5 CCol and L6 CT neurons (Aim 1a-1d, respectively). In Aim 2, we will record from targeted subtypes of
auditory cortex neurons as mice learn to form a spatiotemporal filter for processing expected sounds. We will
address the hypothesis that L6 CT neurons modify their activity shortly before the onset of expected sounds to
optimize cortical processing of behaviorally relevant signals. In Aim 3, we will test the causal involvement of L6
CT spike patterning for enhanced processing of expected sounds by optogenetically silencing their activity at
key times in well-trained mice (to test necessity) or activating them in naïve mice (to test sufficiency).
Collectively, these experiments will reveal neural circuit mechanisms that support the selection of bottom-up
inputs for enhanced perceptual processing during active listening. By extension, improper regulation of this
circuit could underlie the irrepressible awareness of unwanted or distracting sounds (e.g., attention deficit
hyperactivity disorder) or the perception of sounds that...

## Key facts

- **NIH application ID:** 9868992
- **Project number:** 5R01DC017078-03
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Daniel B. Polley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,298
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868992

## Citation

> US National Institutes of Health, RePORTER application 9868992, Corticofugal Circuits for Active Listening (5R01DC017078-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868992. Licensed CC0.

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