Low volume: Refusal to express the FOXP1 gene impairs song learning in young zebras and language development in some children with autism.
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Muting expression of an autism-related gene in the brains of young zebra birds leaves them unable to learn songs from older birds, a new study reports. But it does not alter their ability to practice and master previously memorized melodies.
The gene, FOXP1, belongs to a family of genes that regulate the expression of other genes, shape the nervous system and language development. People who have lost one copy of FOXP1 have language and intellectual disabilities; Those who do have mutations in the gene often have autism traits.
says study leader Todd Roberts, assistant professor of neuroscience at the center. Medical University of Texas Southwestern in Dallas.
Songbirds like zebra finches learn to sing by imitating adult birds, just as young children learn language and social skills by simulating caregivers – a process disrupted in autism.
This learning involves creating a memory – of the idea of a song, word, or social behavior, such as waving – and then practicing that preserved folly or working to perfect it. The new study suggests that FOXP1 plays a role in the first step in this process.
“It shows that we can start to separate these different aspects of learning,” says Roberts.
And other research found that turning off another gene linked to autism, CNTNAP2, in regions of the brain associated with songs, also impairs zebra birds’ ability to learn songs. FOXP2, a gene closely related to FOXP1, is also involved in song learning in birds.
But relatively little is known about FOXP1’s role in vocal learning, says John Sakata, associate professor of biology at McGill University in Montreal, Canada, who was not involved in the work. “I think the experimental design and the results are very convincing in terms of learning.”
Roberts and his team designed a molecule that partially blocks expression of FOXP1 and injected it into the brains of male zebras at about 35 days old – an age at which birds typically engage in song preservation.
The researchers targeted the injection into an area called HVC, which roughly corresponds to specific speech-related regions in the human brain cortex and plays a key role in song learning and production in songbirds.
Cells throughout HVC express FOXP1, especially neurons that connect to another song-related brain region called region X. Birds treated with the inhibiting FOXP1 molecule had about half the normal amount of FOXP1 in these neurons.
Roberts and colleagues predicted that the scarcity of FOXP1 would hinder the practice and perfection stage of song learning, based on previous research. The team found that birds that heard singing before FOXP1 crashed grew up to sing typical zebra bird songs.
“It really surprised us,” says Roberts.
Therefore, the researchers turned to zebra finches that were raised in isolation without having a chance to preserve the sounds of adult birds. They injected these birds with FOXP1 inhibitor and then placed them in a cage with an adult ‘teacher’.
Repeat after me: Young zebras learn songs from adult teachers in two parts, by memorizing the songs and then practicing with them.
“It kind of was a last-ditch effort on the project,” says Roberts. “And then when we saw this huge effect.”
Birds that had a FOXP1 expression before hearing the teacher’s song grew to sing variable, disorganized songs – just like those of adult birds who did not hear adult birds’ voices during their youth.
The results indicate that FOXP1 “has a very specific effect, only on the ability to encode memories of the social model that you want to imitate,” says Roberts. The study appeared February 3 in Science Advances.
The new study does not address the role of FOXP2 in the song preservation process, says Godron Rapold, a geneticist at the University of Heidelberg in Germany who was not involved in the work. The proteins encoded by FOXP1 and FOXP2 form complexes with each other, and both interact with CNTNAP2. Future research should aim to discover how FOXP2 interacts with FOXP1 in HVC when birds form memories of the teacher’s song, Rappold and Sakata say.
Roberts and his team also investigated how dampened FOXP1 expression affects brain activity when birds hear a teacher’s song.
They found that the deficiency in the FOXP1 protein made the neurons that connect HVC and the X region less excited than normal, while these neurons usually become more excited when the bird is first exposed to the guru song. It also disrupted the regulation of neural activity to “bursts” – something that usually happens when birds hear the teacher’s song for the first time.
Exposure to adult bird sounds also increases the abundance of AMPA receptors relative to NMDA receptors on HVC neurons. But this transformation did not happen to birds that were exposed to a FOXP1 inhibitor before hearing the teacher’s song.
Finally, the scarcity of FOXP1 slowed the rotation of dendritic spines, which are protrusions involved in receiving messages sent between neurons, a process known to help birds learn teacher songs.
“These are all classic and very strong links to learning and memory formation,” Roberts says, and they are all disrupted by the loss of FOXP1.
Sakata says that inhibition of FOXP1 in HVC not only affects neurons that connect to the X region. So other HVC neurons could also be important for encoding song memories, as is the case with FOXP1 in other brain circuits. For example, interference with FOXP1 in the X region also impairs song learning in zebra finches, according to other research.
Roberts plans to conduct similar experiments in other brain regions involved in song learning and song production.