This proposal arises out of a long-term effort by the PI to define the molecular mechanisms underlying behavioral plasticity, using songbirds as a model. Previous studies have shown that induction of a specific gene (""""""""ZENK"""""""") occurs in specific parts of the songbird forebrain, in response to a normal perceptual experience -- hearing the sound of other birds singing. We have now found that this ZENK gene response is modified by recent experience: if a particular song is repeated for an hour the response to that song fades, but a new conspecific song from a different individual will immediately reinduce it.
The aim of this project is to assess the functional significance of this experience- dependent change in gene expression in the brain. To this end, we will determine whether specific electrophysiological responses occur in response to conspecific birdsong in the caudomedial neostriatum (""""""""NCM""""""""), which is the primary site of ZENK gene induction and an avian homolog of mammalian neocortex. Experience-dependent physiological responses will be analyzed by counting the number of spikes elicited during auditory stimulus presentation, using """"""""near-single-unit"""""""" recording techniques. In preliminary studies, we have successfully made such measurements in NCM in zebra finches, and have found evidence for a variety of song-selective changes in auditory responses.
The specific aims of the proposed study are to: l) characterize the selectivity of auditory responses in NCM and related brain regions; 2) determine whether ZENK induction is anatomically correlated with sites of physiological plasticity; 3) determine whether production of ZENK protein is temporally correlated with consolidation of physiological change; 4) evaluate whether ZENK induction may have a role in song learning in juveniles; 5) evaluate whether ZENK induction is correlated with other specific behavioral changes in adults. A role for gene expression in guiding the brain's response to experience has long been hypothesized, and the songbird has unique advantages as a model system for testing this hypothesis. These advantages include a controlled perceptual stimulus (song), a defined neural circuit within parts of the brain homologous to the mammalian neocortex, and now the identification of specific gene responses within this circuitry. Clarification of the role gene expression plays in the brain's response to experience could have a major impact on our ability to analyze and treat numerous psychiatric, neurodegenerative and learning disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH052086-01A1
Application #
2251675
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1995-03-01
Project End
1999-02-28
Budget Start
1995-03-01
Budget End
1996-02-29
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Organized Research Units
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Huesmann, Graham R; Clayton, David F (2006) Dynamic role of postsynaptic caspase-3 and BIRC4 in zebra finch song-response habituation. Neuron 52:1061-72
Kruse, Amy A; Stripling, Roy; Clayton, David F (2004) Context-specific habituation of the zenk gene response to song in adult zebra finches. Neurobiol Learn Mem 82:99-108
Cheng, Hui-Yun; Clayton, David F (2004) Activation and habituation of extracellular signal-regulated kinase phosphorylation in zebra finch auditory forebrain during song presentation. J Neurosci 24:7503-13
Stripling, Roy; Milewski, Lynn; Kruse, Amy A et al. (2003) Rapidly learned song-discrimination without behavioral reinforcement in adult male zebra finches (Taeniopygia guttata). Neurobiol Learn Mem 79:41-50
Hartman, V N; Miller, M A; Clayton, D F et al. (2001) Testosterone regulates alpha-synuclein mRNA in the avian song system. Neuroreport 12:943-6
Stripling, R; Kruse, A A; Clayton, D F (2001) Development of song responses in the zebra finch caudomedial neostriatum: role of genomic and electrophysiological activities. J Neurobiol 48:163-80
Holloway, C C; Clayton, D F (2001) Estrogen synthesis in the male brain triggers development of the avian song control pathway in vitro. Nat Neurosci 4:170-5
Kruse, A A; Stripling, R; Clayton, D F (2000) Minimal experience required for immediate-early gene induction in zebra finch neostriatum. Neurobiol Learn Mem 74:179-84
Clayton, D F (2000) The genomic action potential. Neurobiol Learn Mem 74:185-216
Jin, H; Clayton, D F (1997) Localized changes in immediate-early gene regulation during sensory and motor learning in zebra finches. Neuron 19:1049-59

Showing the most recent 10 out of 11 publications