Genetic control of the assembly of circuits involved in vocal learning.


Vocal learning depends on the ability of brain circuits to perceive and imitate sound sequences and use these sequences for communication. Songbirds such as canaries and zebra finches have been a favorite experimental system for the study of vocal learning in animals for decades. These animals exhibit a robust and spontaneous vocal learning behavior, and they have dedicated brain circuits, known as the song system, that participate in the learning and production of song. Zebra finches listen to the songs that their fathers produce, and imitate these sounds until they acquire a stable adult-like song. In this respect, the time course and strategy of vocal learning in zebra finches is very similar to the manner in which human infants learn to speak. These observations suggest that the zebra finch could be an ideal system where to start investigating the genetic and biological basis of vocal learning. Recently, our laboratory has succeeded in the development of a series of techniques that allow us to genetically modify the brain of songbirds. These technical advances open new opportunities for the study of the relationship between genes and learning in an animal species with a robust behavioral repertoire. We are currently generating transgenic songbirds to manipulate key genes involved in the assembly of circuits involved in vocal learning behavior.

  Genetically modified songbirds to investigate the molecular bases of vocal learning and complex behavior.   Our lab has developed several techniques to genetically manipulate the development and function of neurons during the assembly of neuronal circuits. We have recently developed new genetic methods that have allowed us to generate transgenic songbirds to investigate the genetic basis of the assembly of brain circuits involved in vocal communication. We are using these transgenic songbirds to investigate the rules by which neurons migrate, choose their final locations, establish connections with each other, and give rise to behavior.

Genetically modified songbirds to investigate the molecular bases of vocal learning and complex behavior.

Our lab has developed several techniques to genetically manipulate the development and function of neurons during the assembly of neuronal circuits. We have recently developed new genetic methods that have allowed us to generate transgenic songbirds to investigate the genetic basis of the assembly of brain circuits involved in vocal communication. We are using these transgenic songbirds to investigate the rules by which neurons migrate, choose their final locations, establish connections with each other, and give rise to behavior.

 

  Transgenic songbirds with a targeted mutation for the autism-related gene CNTNAP2.   We have generated transgenic songbirds targeting the autism-related gene CNTNAP2 and have observed that the mutant birds fail to accurately copy their tutor’s song. (Bottom right) Wild-type siblings copy the song of their fathers very accurately, but mutant birds fail to copy the parts of the song that are acoustically complex. We are investigating how perturbation of CNTNAP2 affects the assembly of brain circuits involved in learning and production of songs.

Transgenic songbirds with a targeted mutation for the autism-related gene CNTNAP2.

We have generated transgenic songbirds targeting the autism-related gene CNTNAP2 and have observed that the mutant birds fail to accurately copy their tutor’s song. (Bottom right) Wild-type siblings copy the song of their fathers very accurately, but mutant birds fail to copy the parts of the song that are acoustically complex. We are investigating how perturbation of CNTNAP2 affects the assembly of brain circuits involved in learning and production of songs.

 

  Genetic manipulation of activity and robustness of behavior.   We have observed that delivering a voltage-gated sodium channel to render neurons in the song system hyperexcitable leads to acute degradation of the song. Surprisingly, the song structure recovers very quickly (within 10 days) after the genetic manipulations. We are currently investigating the mechanisms responsible for this recovery.

Genetic manipulation of activity and robustness of behavior.

We have observed that delivering a voltage-gated sodium channel to render neurons in the song system hyperexcitable leads to acute degradation of the song. Surprisingly, the song structure recovers very quickly (within 10 days) after the genetic manipulations. We are currently investigating the mechanisms responsible for this recovery.