Experience plays a critical role in shaping the structural and functional properties of the developing central nervous system. When experience is rich and normal, it leads to a brain that is optimized for the individual. When experience is chronically abnormal, however, as a consequence of disease, defects, injury or dysfunction, for example, experience can lead to abnormal structure and function. For the many pathways that are subject to sensitive periods, these effects result in permanent neurological disability. The proposed research investigates, at the systems, cellular and molecular levels, the effects of experience on the developing central auditory system. The research focuses on the pathways that process spatial information, pathways that are known in relative detail. The effects of experience on these pathways are dramatic and readily quantified. The barn owl is studied because the space processing pathways are particularly well developed in this species, and the sensitive periods have been established. Extracellular neurophysiological, pharmacological and anatomical techniques will be combined with dichotic sound stimulation to characterize both the effects of abnormal sensory experience and the ability of the auditory system to recover normal function following restoration of normal experience. The effects of two different sensory challenges will be compared: abnormal vision and abnormal hearing. In the midbrain space processing pathway, where sites of plasticity are already known, the research emphasizes the cellular and molecular mechanisms of plasticity and sensitive periods (the roles of anatomical reorganization, specific neurotransmitter receptors, neurotrophins, and sex steroids). Also, the anatomical source and nature of the instructive signal that governs this plasticity will be explored. In the forebrain space processing pathway, the research concentrates on identifying sites of plasticity and characterizing the properties of the plasticity.
This research aims to provide a mechanistic understanding of the effects of experience on the developing central auditory system. Knowledge of the aspects of neuronal connectivity that are altered by experience and how these alterations are implemented may lead to improved therapeutic strategies for the many individuals who suffer from or have suffered from prolonged periods of abnormal sensory experience. In addition, the results should teach us much about the normal structure, function and development of the central auditory system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000155-23
Application #
6516020
Study Section
Hearing Research Study Section (HAR)
Program Officer
Luethke, Lynn E
Project Start
1980-04-01
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
23
Fiscal Year
2002
Total Cost
$387,411
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Witten, Ilana B; Knudsen, Phyllis F; Knudsen, Eric I (2010) A dominance hierarchy of auditory spatial cues in barn owls. PLoS One 5:e10396
Bergan, Joseph F; Knudsen, Eric I (2009) Visual modulation of auditory responses in the owl inferior colliculus. J Neurophysiol 101:2924-33
Winkowski, Daniel E; Knudsen, Eric I (2008) Distinct mechanisms for top-down control of neural gain and sensitivity in the owl optic tectum. Neuron 60:698-708
Witten, Ilana B; Knudsen, Eric I; Sompolinsky, Haim (2008) A Hebbian learning rule mediates asymmetric plasticity in aligning sensory representations. J Neurophysiol 100:1067-79
Winkowski, Daniel E; Knudsen, Eric I (2007) Top-down control of multimodal sensitivity in the barn owl optic tectum. J Neurosci 27:13279-91
Winkowski, Daniel E; Knudsen, Eric I (2006) Top-down gain control of the auditory space map by gaze control circuitry in the barn owl. Nature 439:336-9
DeBello, William M; Knudsen, Eric I (2004) Multiple sites of adaptive plasticity in the owl's auditory localization pathway. J Neurosci 24:6853-61
Knudsen, Eric I (2004) Sensitive periods in the development of the brain and behavior. J Cogn Neurosci 16:1412-25
Miller, Greg L; Knudsen, Eric I (2003) Adaptive plasticity in the auditory thalamus of juvenile barn owls. J Neurosci 23:1059-65
Gold, J I; Knudsen, E I (2001) Adaptive adjustment of connectivity in the inferior colliculus revealed by focal pharmacological inactivation. J Neurophysiol 85:1575-84

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