The long-term goal of this grant is to understand the neural mechanisms for auditory-guided vocal learning. The objective addressed in this application is to identify molecular signatures of functional circuits for vocal motor learning. The learned song of songbirds is the best characterized exemplar of vocal learning, however few of the molecules that define and operate within the functional circuitry are known. Traditional laboratory species do not modify their innate vocalizations, so it has been improbable, until now, to test a molecule identified in the vocal learning of another animal group for its function birdsong. This improbability has changed with the identification of FOXP2 as the first monogenetic locus for a human language disorder. The core deficit of humans bearing a FOXP2 mutation is in the accuracy and consistency and human speech and in generating sequential movements of the orpfacial musculature. This behavioral phenotype is accompanied by abnormal structure and function of a cortical-striatal circuit that participates in speech. Together, these findings indicate that FOXP2 lies along one neural path linked to speech. We propose to use molecular, behavioral, and genetic intervention techniques in songbirds to discover the role of FoxP molecules in the vocal learning circuit of the zebra finch. Songbirds are ideal for these studies as a corticalstriatal circuit underlies song production and development. Further, each of the three phases of song learning can be extended or exaggerated by manipulating auditory input. Therefore, any developmental correlations observed for candidate neural mechanisms of vocal learning can be secondarily screened to determine whether the correlation persists beyond chronological age to behavioral state. The songbird thereby offers an unrivalled opportunity for screening candidate molecules prior to selecting them for functional tests.
Specific Aim 1 will determine whether FoxP neural expression patterns are regulated during song learning.
Specific Aim 2 tests the hypothesis that changes in FoxP expression correlate specifically with the sensorimotor phase of song learning and song maintenance.
Specific Aim 3 uses altered genetic expression of FoxP molecules to test whether they are necessary for sensorimotor learning and song maintenance. These findings will significantly advance our understanding of the formation and function of vocal-learning circuitry. Discovery of FoxP function in songbirds, the only experimentally tractable vocal learner, will additionally provide essential information regarding human disorders linked to FOXP mutations ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH070712-02
Application #
7102744
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Vicentic, Aleksandra
Project Start
2005-08-01
Project End
2010-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$254,577
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Burkett, Zachary Daniel; Day, Nancy F; Kimball, Todd Haswell et al. (2018) FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch. Elife 7:
Heston, Jonathan B; White, Stephanie A (2017) To transduce a zebra finch: interrogating behavioral mechanisms in a model system for speech. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 203:691-706
Fraley, E R; Burkett, Z D; Day, N F et al. (2016) Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns. Sci Rep 6:25807
Berg, Jamee M; Lee, Changhoon; Chen, Leslie et al. (2015) JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse. Neuron 88:1173-1191
Burkett, Zachary D; Day, Nancy F; Pe├▒agarikano, Olga et al. (2015) VoICE: A semi-automated pipeline for standardizing vocal analysis across models. Sci Rep 5:10237
Hara, Erina; Perez, Jemima M; Whitney, Osceola et al. (2015) Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult vocal learning. Behav Brain Res 283:22-9
Whitney, Osceola; Voyles, Tawni; Hara, Erina et al. (2015) Differential FoxP2 and FoxP1 expression in a vocal learning nucleus of the developing budgerigar. Dev Neurobiol 75:778-90
Heston, Jonathan B; White, Stephanie A (2015) Behavior-linked FoxP2 regulation enables zebra finch vocal learning. J Neurosci 35:2885-94
Condro, Michael C; White, Stephanie A (2014) Recent Advances in the Genetics of Vocal Learning. Comp Cogn Behav Rev 9:75-98
Grant, Laura M; Richter, Franziska; Miller, Julie E et al. (2014) Vocalization deficits in mice over-expressing alpha-synuclein, a model of pre-manifest Parkinson's disease. Behav Neurosci 128:110-21

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