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Principal Investigator: Richard D Mooney
Organization: DUKE UNIVERSITY
Fiscal Year: 2024
Award: $416,779
Funding agency: National Institute on Deafness and Other Communication Disorders
Project Summary
Vocal communication depends on distinguishing our own vocal sounds (vocal feedback) from other sounds.
Vocal motor-related corollary discharge (vocal CD) signals that suppress auditory responses to predictable
vocal feedback help make this distinction. Notably, vocal CD signals in the human auditory cortex are
especially important to speech and their dysfunction is thought to cause auditory hallucinations. Despite the
key roles postulated for vocal CD signals, the challenges of monitoring and manipulating their activity in
vocalizing animals has prevented systematic analyses. The long-term objective of this application is to
understand with synaptic, cellular, and circuit resolution how vocal CD signals modulate auditory cortical
responses to vocal feedback, detailed knowledge of which is essential to understand adaptive and maladaptive
aspects of audition. We will gain detailed knowledge of synaptic, cellular, and circuit mechanisms underlying
this process by studying the mouse, the vertebrate most suited to advanced genetic, electrophysiological, and
optical tools. In the prior funding period, we used these tools to advance our understanding the synaptic and
circuit mechanisms by which movement-related CD signals modulate auditory cortical activity. These
advances included mapping a motor to auditory cortical circuit, determining that various head and body
movements activate this pathway to suppress auditory cortical responses to sounds, and showing that this
pathway can “learn” to selectively suppress sounds that are predictably yoked to locomotor movements. We
also observed auditory cortical suppression in vocalizing male mice, but vocalization occurred during female
courtship and was always accompanied by other movements, as well as by social and sexual stimuli.
Therefore, whether vocalization-specific CD signals modulate the auditory cortex and suppress predictable
vocal feedback remain unknown. Fortunately, we also developed methods for optogenetically gating ultrasonic
vocalizations (USVs) and for distorting vocal feedback in the isolated, head-fixed mouse. Here we propose to
combine these methods with other state of the art techniques, including multi-electrode arrays, in vivo
multiphoton imaging, controlled manipulation of vocalization-related auditory feedback, and novel
computational methods for voco-acoustic analysis. In the first Aim, we will test the idea that vocalization
suppresses auditory cortical activity and use machine learning methods to rigorously quantify and compare
spontaneous and optogenetically-evoked USVs. In the second Aim, we will isolate cortical contributions to the
vocal modulation of auditory cortical activity. In the third Aim, we will distort vocal feedback to determine if
vocal suppression of the auditory cortex is predictive, and use computational methods to systematically
quantify vocal distortion. Together, these Aims will provide novel insights into the synaptic, cellular, and circuit
mechanisms by which vocal CD signals influence auditory cortical processing.
Terms: <2-photon><Acoustics><Address><Animal Vocalization><Arousal><Auditory><Auditory Cortex><Auditory Hallucination><Auditory area><Auditory system><Behavior><Behavioral><Bone Conduction><Brain><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Communication><Complex><Computing Methodologies><Connector Neuron><Courtship><Disease><Disorder><Dysfunction><Electrodes><Electrophysiology><Electrophysiology (science)><Encephalon><Feedback><Female><Functional disorder><Funding><Genetic><Goals><Grant><Head><Head Movements><Health><Hearing><Human><Image><Impairment><Intercalary Neuron><Intercalated Neurons><Interneurons><Internuncial Cell><Internuncial Neuron><Intracellular Communication and Signaling><Knowledge><Learning><Locomotion><Maps><Measures><Methods><Mice><Mice Mammals><Modern Man><Monitor><Monkeys><Motor><Motor Cortex><Movement><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Optical Methods><Optics><Pathway interactions><Physiologic><Physiological><Physiopathology><Process><Production><Property><Pyramidal Cells><Resolution><Signal Transduction><Signal Transduction Systems><Signaling><Social Environment><Social isolation><Speech><Stimulus><Synapses><Synaptic><Techniques><Testing><Thalamic structure><Thalamus><Time><Ultrasonic><Ultrasonics><Work><auditory feedback><auditory processing><auditory stimulus><autoencoder><autoencoding neural network><biological signal transduction><body movement><bone conduction hearing><bone-conducted hearing><computational methodology><computational methods><computer based method><computer methods><computing method><deaf><deafened><electrophysiological><excitatory neuron><experience><experiment><experimental research><experimental study><experiments><flexibility><flexible><good hearing><healthy hearing><imaging><in vivo><inhibitory neuron><insight><machine learning based method><machine learning method><machine learning methodologies><male><multi-electrode arrays><multi-photon imaging><multielectrode arrays><multiphoton imaging><neuronal><normal hearing><novel><optical><optogenetics><pathophysiology><pathway><prevent><preventing><profound hearing loss><resolutions><response><social><social climate><social context><socioenvironment><socioenvironmental><sound><synapse><thalamic><tool><two-photon><unsupervised learning><unsupervised machine learning><vocalization>