Adaptive plasticity in the central nervous system is essential for the recovery of function following injury, stroke or neurological disease or following the restoration of hearing with prosthetics. Although the capacity for brain plasticity is great during early life, it becomes substantially more restricted in adults. This research focuses on the capacity for plasticity in the adult central nervous system, the factors that control it, and ways to maximize it. We will explore the mechanisms by which experience shapes the functional and anatomical properties of the central auditory system in adult barn owls. In the midbrain auditory localization pathway, adaptive changes in cellular structure and function can be quantified rigorously and detected with high sensitivity. Manipulations of sensory experience cause dramatic functional, physiological and anatomical changes in juvenile owls. This research will test the effects of similar manipulations of experience on adult owls and will explore environmental and psychological factors that may regulate this plasticity. Reorganization of the midbrain auditory pathway will be induced in adults by exposing them to various proven regimes of sensory experience. Plasticity will be assessed with behavioral, neurophysiological, anatomical and pharmacological techniques. The influence of attention and arousal on plasticity will be determined by exposing owls to sessions of sensorimotor enrichment. In addition, the effects of natural stressors, such as social dominance, crowding and environmental change, on cellular plasticity will be measured. The mechanisms of action of these psychological factors (attention, arousal and stress) and the neuromodulatory systems that they engage will be investigated. We will compare and contrast the mechanisms of plasticity in adults with those that have been shown to operate in juveniles. The results of this research will increase our understanding of exactly how experience shapes the functional properties of the adult central auditory system. Knowledge of the cellular mechanisms that underlie adaptive plasticity and of the regulation of these mechanisms by psychological state will help to formulate optimal strategies for teaching and optimal therapies for rehabilitation following brain injury, disease or remediation of genetic defects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000155-27
Application #
7064777
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Luethke, Lynn E
Project Start
1980-04-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
27
Fiscal Year
2006
Total Cost
$359,685
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
009214214
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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