Seasonal growth and shrinkage of brain regions involved in control of birdsong provides a striking and unique opportunity to investigate the mechanisms regulating neuronal turnover associated with natural variation in steroids, and the functional consequences of this neural plasticity for sensorimotor learning.
The aims i n this proposal address fundamental issues of neural plasticity, and neuronal turnover in particular, in adult brains. These include the role of steroid hormones and neurotrophins in neuronal birth and death (Aims 1-2), the role of neurotrophins in neuronal activity that influences neurogenesis (Aim 3), and the coordinated expression of families of genes important in regulating functionally related processes of neurogenesis, neuronal protection, death, and activity (Aim 4). The birdsong system excels as a model for studies of neural plasticity;it is a well-defined and tractable neural circuit that shows extreme seasonal plasticity and regulates song, a learned sensorimotor behavior that is easily analyzed. This research will advance the field by 1) elucidating the mechanisms underlying the functional linkage between neuronal birth and death in adult brains (Aims 1,2);2) providing the first evidence that neurotrophins influence the electrophysiology of neurons in the song system (Aim 3);3) moving this field beyond the level of single gene analysis by opening up analysis of microRNA expression as a molecular mechanism for coordinating the expression of gene families that regulate the component cellular processes of adult neuroplasticity (Aim 4).

Public Health Relevance

Steroid hormones have potential for use as neuroprotective agents in the treatment of stroke and a variety of neurodegenerative and mental health disorders. They are also of increasing concern as drugs of abuse. This work will examine the fundamental mechanisms by which these potent hormones influence neuronal birth, death, and gene expression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Sensorimotor Integration Study Section (SMI)
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Glanzman, Dennis L
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University of Washington
Schools of Arts and Sciences
United States
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Brenowitz, Eliot A (2015) Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity. Front Neuroendocrinol 37:119-28
Larson, Tracy A; Thatra, Nivretta M; Lee, Brian H et al. (2014) Reactive neurogenesis in response to naturally occurring apoptosis in an adult brain. J Neurosci 34:13066-76
Brenowitz, E A (2013) Testosterone and brain-derived neurotrophic factor interactions in the avian song control system. Neuroscience 239:115-23
Larson, Tracy A; Wang, Tsu-Wei; Gale, Samuel D et al. (2013) Postsynaptic neural activity regulates neuronal addition in the adult avian song control system. Proc Natl Acad Sci U S A 110:16640-4
Templeton, Christopher N; Burt, John M; Campbell, S Elizabeth et al. (2012) Immediate and long-term effects of testosterone on song plasticity and learning in juvenile song sparrows. Behav Processes 90:254-60
Thompson, Christopher K; Meitzen, John; Replogle, Kirstin et al. (2012) Seasonal changes in patterns of gene expression in avian song control brain regions. PLoS One 7:e35119
Thompson, Christopher K; Brenowitz, Eliot A (2010) Neuroprotective effects of testosterone in a naturally occurring model of neurodegeneration in the adult avian song control system. J Comp Neurol 518:4760-70
Fraley, Gregory S; Steiner, Robert A; Lent, Karin L et al. (2010) Seasonal changes in androgen receptor mRNA in the brain of the white-crowned sparrow. Gen Comp Endocrinol 166:66-71
Wissman, Anne Marie; Brenowitz, Eliot A (2009) The role of neurotrophins in the seasonal-like growth of the avian song control system. J Neurosci 29:6461-71
Meitzen, John; Weaver, Adam L; Brenowitz, Eliot A et al. (2009) Plastic and stable electrophysiological properties of adult avian forebrain song-control neurons across changing breeding conditions. J Neurosci 29:6558-67

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