The brain must be able to separate and distinguish sensations arising from our own movements (reafferent stimuli) from those arising from objects in our environment (exafferent stimuli). This is believed to occur via a corollary discharge signal or a copy of the motor plan projected onto sensory processing brain regions, that suppress reafferent auditory sensations to facilitate accurate perception of the auditory environment. A large body of research indicates that dysfunction of corollary discharge circuits, particularly those related to audition, is linked to debilitating physical and mental disorders, notably the auditory hallucinations characteristic of psychoses. Despite the importance of corollary discharge circuits in the normal and diseased brain, remarkably little is known about the neural circuits and synaptic mechanisms responsible for the generation and propagation of corollary discharge signals important to hearing. Here I propose a series of innovative physiological, optogenetic, and behavioral experiments in mouse to measure and identify corollary discharge signals related to naturalistic behaviors including vocalization, grooming, and locomotion, and to test the hypothesis that specific populations of motor cortical neurons that send axon collaterals to the auditory cortex are the source of these corollary discharge signals. I will utilize a custom make miniature, motorized microdrive to make intracellular recordings from the auditory cortex during unrestrained movements and periods of rest. I will use tests of postsynaptic input impedance and neuronal excitability to test the hypothesis that movement-related corollary discharge directly modulates auditory cortical processing through local inhibition in the auditory cortex, consistent with a cortico-cortical model of corollary discharge. I will then use optogeneti manipulation to silence a population of motor cortical neurons that projects to the auditory cortex, testing the hypothesis that these neurons are responsible for the genesis of a corollary discharge signal. Completion of this project will detail a synaptic and circuit mechanism that mediates movement-related corollary discharge signals in the auditory cortex.

Public Health Relevance

Distinguishing sensory information generated by our own movements from sensory information arising from objects in our environment (corollary discharge) is critical to maintaining an accurate representation of the world around us. Dysfunction of corollary discharge is believed to underlie debilitating symptoms of neurological disorders, including the auditory hallucinations characteristic of schizophrenia. This proposal seeks to understand the synaptic and circuit mechanisms governing auditory corollary discharge, and as such, will be valuable in understanding how these circuits function in both health and disease.

Agency
National Institute of Health (NIH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DC013976-01
Application #
8717134
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Sklare, Dan
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Biology
Type
Schools of Medicine
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705