Investigating the role of CNTNAP2 gene in vocal learning in mutant songbirds

Summary

Principal Investigator: Carlos Lois
Abstract: DESCRIPTION (provided by applicant): Communication impairments are some of the most debilitating consequences of a number of neurodevelopmental disorders, including autism spectrum disorders (ASD). It is thought that the communication impairments associated with neurodevelopmental disorders may be due to the perturbed assembly of brain areas involved in vocal communication. In recent years a number of genes, including the transcription factor FoxP2 and its target CNTNAP2, have been linked to language specific impairments and to ASD in humans, suggesting that they could play a direct role in speech and language acquisition. However, the lack of adequate animal models to specifically study vocal learning and communication has prevented the dissection of the genetic components involved in communication behaviors. Songbirds are currently the best animal model to study vocal communication because song learning in these animals shares critical features with speech acquisition in humans. Moreover, songbirds have a dedicated brain circuit that is required for the learning and production of vocal signals. Finally, both Foxp2 and CNTNAP2 are expressed in the song system suggesting that speech acquisition in humans and song learning in songbirds involves similar molecular pathways. Thus, songbirds could be an excellent model to study the genetic basis of communication-related aspects of neurodevelopmental disorders, as they represent the ideal system to study how genes orchestrate the assembly of a brain circuit dedicated to vocal learning and production. Our laboratory has developed new methods for the genetic modification of songbirds that will enable us and other researchers to generate genetic animal models for vocal communication disorders. In this proposal we describe a plan to generate genetically-engineered songbirds deficient in CNTNAP2, which will open a new avenue for investigating the role of genes on the assembly and function of the brain circuits involved in vocal communication. This approach should lead to a better understanding on how mutations in this and other genes result in communication deficits such as the ones observed in patients with ASD and other neurodevelopmental disorders.
Funding Period: 2012-08-13 - 2014-07-31
more information: NIH RePORT

Detail Information

Research Grants30

  1. Behavioral and Neural Analysis of vocal Plasticity
    Michael S Brainard; Fiscal Year: 2013
    ..abstract_text> ..
  2. A Gene Expression Brain Atlas of the Zebra Finch.
    Claudio V Mello; Fiscal Year: 2013
    ..singing behavior and vocal learning. ..
  3. IDDRC at Children's Research Institute
    Vittorio Gallo; Fiscal Year: 2013
    ..abstract_text> ..
  4. The role of stress and FoxP2 in adult vocal learning: tests using a parrot model
    Timothy F Wright; Fiscal Year: 2013
    ..This project will examine the effects of social context and stress in an animal model for adult vocal learning, the budgerigar. It will also investigate the physiological and genetic mechanisms that underlie adult vocal learning. ..
  5. Organization and experience-dependence of auditory coding in forebrain
    ALLISON JANE DOUPE; Fiscal Year: 2013
    ....
  6. Transgenesis in songbirds for the genetic manipulation of neuronal circuits
    Carlos Lois; Fiscal Year: 2013
    ..We propose to develop new molecular tools that will allow for genetic manipulation of songbirds to generate animal models of human diseases that affect complex cognitive functions and communication disorders. ..
  7. Core Center for Integrated Research on Human Communication Disorders
    Charles R Larson; Fiscal Year: 2013
    ..The innovative outcome of this project will be the establishment of screening tests and experimental protocols that are most reliable for identifying markers of underlying etiologies of disorders of communication. ..
  8. Formation and Function of Circuitry for Vocal Learning
    Stephanie Ann White; Fiscal Year: 2013
    ..These studies will provide basic but critical information about the neural processes underlying a complex socially-learned behavior. ..
  9. SRC on Primary Tumors of the CNS
    Darell D Bigner; Fiscal Year: 2013
    ..Cores A and C are currently funded;Core B is a continuation from earlier grant periods. ..
  10. BEHAVIORAL MECHANISMS OF VOCAL IMITATION
    Ofer Tchernichovski; Fiscal Year: 2013
    ..abstract_text> ..
  11. Neural Coding and Perception of Learned Vocalizations
    SARAH M WOOLLEY; Fiscal Year: 2013
    ..The neural mechanisms of vocal perception that are described in this work may suggest candidate mechanisms for how auditory training alters human brain processing of speech sounds and how speech acquisition shapes speech processing. ..
  12. Characteristics of Prelinguistic Vocalizations that Facilitate Social Feedback
    Michael H Goldstein; Fiscal Year: 2013
    ..By simulating interactions with infants whose vocal development is affected by developmental disorders, the playback paradigm could become a useful intervention tool. ..
  13. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
    ..abstract_text> ..
  14. A Family-Genetic Study of Language in Autism
    MOLLY C LOSH; Fiscal Year: 2013
    ..Research aimed at uncovering the pathogenesis of autism may lead to evidence-based approaches to prevention or treatment. ..
  15. Grammatical Development in Boys with Fragile X Syndrome and Autism
    AUDRA MARIE STERLING; Fiscal Year: 2013
    ..Additionally, by examining the impact of autism on fragile X, the proposed project will suggest hypotheses about neural constraints on language development, which is relevant to the mission of NIDCD and the NIH as a whole. ..
  16. Baylor Intellectual and Developmental Disabilities Research Center
    Huda Y Zoghbi; Fiscal Year: 2013
    ..abstract_text> ..
  17. Neurobehavioral Research on Infants at Risk for SLI and Autism
    HELEN B TAGER-FLUSBERG; Fiscal Year: 2013
    ..abstract_text> ..
  18. AUDITORY MEMORIES AND VOCAL LEARNING
    Frederic E Theunissen; Fiscal Year: 2013
    ..Our work could also be instrumental in the development of novel signal processing methods for auditory neural prosthetics. ..