How do rapid variations of the waking state influence central auditory responses and what is the role of noradrenergic and cholinergic systems? The central hypothesis that we wish to examine is ?Rapid modulation of the waking state result from variations in activity of the noradrenergic and cholinergic pathways and occur along a continuum from: 1) reduced responses owing to cortical/subcortical spontaneous slow rhythms/low frequency cell and network burst firing during low arousal, 2) quiescent but accurately responsive networks during intermediate alertness, and 3) reduced responsiveness during high arousal or walking owing to high levels of both excitatory and inhibitory spontaneous activity. This is a timely topic, given that modulation of auditory responses and processing is important not only to normal hearing, but also in the recovery of function following damage or disease. Here we will test our central hypothesis (stated above) by performing extracellular unit and whole cell (synaptic) recordings from auditory cortical neurons and related subcortical structures (medial geniculate, inferior colliculus) during precisely measured variations in the waking state along with monitoring and manipulating the the activity of ascending cholinergic and noradrenergic pathways. Together, these results will yield a significant increase in our understanding of the cellular and network mechanisms of both normal, and recovery, of auditory cortical and subcortical function.

Public Health Relevance

Rapid modulation of auditory processing is important not only to normal behavior, but also recovery of function. Here we will examine the hypothesis that rapid modulation occurs through cholinergic and noradrenergic determination of network activities and that this knowledge may facilitate the design of therapeutics for the recovery of function following insult or injury. Using state-of-the-art methodologies, we will determine the precise synaptic and neuronal mechanisms by which rapid variations in the waking state influence and control sound processing by the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC015803-01
Application #
9213960
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Poremba, Amy
Project Start
2016-12-01
Project End
2017-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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