Hearing loss is a major cause of morbidity and social disengagement in the aging population. Unfortunately, hearing aids, which compensate for the peripheral deficits, do not adequately enhance the intelligibility of speech in real-world situations. This is because a major cause of age-relating hearing loss is the dysfunction of central mechanisms that allow the brain to selectively attend to particular streams of auditory input. One hypothesis to explain the breakdown in this selective attention process is the particular vulnerability of cortical inhibition in the aging brain. We propose to examine the role of age-related loss of inhibition in one neural system that has been implicated in selective auditory attention: the auditory corticothalamic system. We have previously shown that auditory corticothalamic neurons in young adult mice are under substantial inhibitory control and that multiple distinct inhibitory microcircuits exist within the corticothalamic system. We hypothesize that there is an age-associated loss of particular elements within this inhibitory microcircuitry. We will investigate age-related changes in the inhibitory circuitry onto identified auditory corticothalamic neurons using laser scanning photostimulation of caged glutamate in the slice preparation. Specifically, based on our previous work, we will study three particular sets of inhibitory inputs: GABAAergic inputs from layers 2/3 and 5 onto layer 5 corticothalamic neurons and layer 6-derived GABAAergic inputs onto layer 6 corticothalamic neurons. We will also investigate age-related changes in the functional mapping of cortical inputs onto thalamic neurons. We hypothesize that decreases in cortical inhibition will produce a broadening of cortical input onto thalamic cells, and that this may be responsible for the selective auditory attention deficits described above. We will record from individual thalamic neurons in the auditory corticothalamic slice preparation and construct cortical input maps using laser scanning photostimulation. Maps will be compared between young and aged mice and it is expected that aging will broaden these inputs. Our longer term goals are to extend this work to the in vivo preparation to correlate potential age-associated changes in corticothalamic mapping to particular auditory attention deficits. The proposed work will lead to a greater understanding of the mechanisms responsible for age-associated central auditory dysfunction, and may ultimately provide therapeutic targets for amelioration of this highly prevalent condition.

Public Health Relevance

Age-associated hearing loss affects approximately one third of older adults and the proposed work will examine the brain mechanisms of this hearing loss. Specifically, we believe that the root of these difficulties is the inability to suppress distracting sounds and that this is caused by dysfunction of particular sets of brain cells. We will test this idea by examining changes in the brain circuitry of the auditory system in aging animal models.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC012125-02
Application #
8338872
Study Section
Special Emphasis Panel (ZDC1-SRB-R (35))
Program Officer
Platt, Christopher
Project Start
2011-09-26
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$150,854
Indirect Cost
$50,854
Name
University of Illinois Urbana-Champaign
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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Stebbings, K A; Choi, H W; Ravindra, A et al. (2016) Ageing-related changes in GABAergic inhibition in mouse auditory cortex, measured using in vitro flavoprotein autofluorescence imaging. J Physiol 594:207-21
Stebbings, Kevin A; Choi, Hyun W; Ravindra, Aditya et al. (2016) The impact of aging, hearing loss, and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging. Neurobiol Aging 42:101-9
Willis, Adam M; Slater, Bernard J; Gribkova, Ekaterina D et al. (2015) Open-loop organization of thalamic reticular nucleus and dorsal thalamus: a computational model. J Neurophysiol 114:2353-67
Slater, Bernard J; Fan, Anthony Y; Stebbings, Kevin A et al. (2015) Modification of a Colliculo-thalamocortical Mouse Brain Slice, Incorporating 3-D printing of Chamber Components and Multi-scale Optical Imaging. J Vis Exp :
Hasson, Uri; Llano, Daniel A; Miceli, Gabriele et al. (2014) Does it talk the talk? On the role of basal ganglia in emotive speech processing. Behav Brain Sci 37:556-7; discussion 577-604
Llano, Daniel A; Slater, Bernard J; Lesicko, Alexandria M H et al. (2014) An auditory colliculothalamocortical brain slice preparation in mouse. J Neurophysiol 111:197-207
Stebbings, Kevin A; Lesicko, Alexandria M H; Llano, Daniel A (2014) The auditory corticocollicular system: molecular and circuit-level considerations. Hear Res 314:51-9
Llano, Daniel A (2013) Functional imaging of the thalamus in language. Brain Lang 126:62-72
Llano, Daniel A (2013) Voices below the surface: is there a role for the thalamus in language? Brain Lang 126:20-1

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