The Human Langauge Gene in Song Birds

A recent paper in PLoS Biology examines the role of the so called "language gene" in neural development related to vocalization. It was previously found that FOXP2 gene is up-regulated in a certain area of the brain that is important for neural plasticity related to vocalization. The present study reduces the levels of expression of FOXP2 gene using "FOXP2 Knockdown" individuals (individuals with a somewhat broken FOXP2 gene) in this area prior to an important stage in brain development that is related to vocalization. The effect on learning vocalization, is negative.

This experiment was done in birds (zebra finches).

This is the author's summary:

Do special "human" genes provide the biological substrate for uniquely human traits, such as language? Genetic aberrations of the human FoxP2 gene impair speech production and comprehension, yet the relative contributions of FoxP2 to brain development and function are unknown. Songbirds are a useful model to address this because, like human youngsters, they learn to vocalize by imitating the sounds of their elders. Previously, we found that when young zebra finches learn to sing or when adult canaries change their song seasonally, FoxP2 is up-regulated in Area X, a brain region important for song plasticity. Here, we reduced FoxP2 levels in Area X before zebra finches started to learn their song, using virus-mediated RNA interference for the first time in songbird brains. Birds with experimentally lowered levels of FoxP2 imitated their tutor's song imprecisely and sang more variably than controls. FoxP2 thus appears to be critical for proper song development. These results suggest that humans and birds may employ similar molecular substrates for vocal learning, which can now be further analyzed in an experimental animal system.

The paper is available on line here, at PLoS, which is an open access peer reviewed journal.

It is believed that the main area of the brain affected by a broken FOXP2 gene in humans is the basal ganglia in humans. This allows the expectation to be advanced that FOXP2 can be studied in a wide range of organisms, because the mammalian basal ganglia is the area of the cortex most likely (along with a couple of other areas) to be homologous to brain areas in other organisms such as birds.

The fact that breaking the FOXP2 system in birds causes neural effects manifest in developmental abnormalities demonstrates that FOXP2 is a gene that has something to do with neural development (and probably other things) and significantly reduces the likelihood that this gene has a human-language specific function. In other words, while the FOXP2 gene may be one of several genes involved in human language, this involvement is analogous to, say the involvement of a steel making plant in the production of a car. One might notice that cars built with the steel from a certain plant tend to have hoods (bonnets) that rust quickly. One could then implicate this steel making plant in the ideation, design, development, and manufacturer of the automobile hood. But, one would eventually have to notice that metal cooking pots, bicycles, cabinets, and all manor of widgets manufactured from the metal supplied by this same plant also seem to rust prematurely. One has not discovered a system related to the automobile hood, but rather, one has discovered something much more general.

Similarly, the fact that FOX2P affects neural development in similar ways in song birds and humans demonstrates the importance of, but also the generality of, FOX2P, which is, affter all, a regulatory gene. The arguement that FOX3P gene is a "human language gene" (an argument already very much in question) is significantly weakened, and at the same time, the idea of a high degree of importance of FOX2P in development is enhanced.

Nonetheless this research is very important in its examination of neural development in vertebrates. In particular, the FOX2P knockdown experiment reveals interesting details about how vocal learning may occur, as an interaction among brain and body parts via motor control systems.

Under the assumption of a model of reinforcement-based motor learning mediated through the basal ganglia, the animal initially generates variable motor output. Progressively, particular motor actions are reinforced ... In view of this model, FoxP2 knockdown pupils might have either experienced a limitation in generating enough sound variability or difficulties with reinforcing the "right" motor patterns, a possibility that includes both difficulties in detecting similarity to the target or adjusting song appropriately.

FOX2P does not confer vocal ability or produce vocal learning. Rather, it has to do with the development of areas of the brain that then engage in an interactive learning scenario in which vocal learning happens by repetition, reinforcement, and ultimately, culling or growth of neurons or changes in neural connections.

A bird with a FOX2P knockdown allele will still learn a song, but not very well. A bird living the absence of bird song ... in the absence of the sociocultural environment that involves bird song ... will produce something that sounds nothing like the original song. A bird with a functioning FOX2P gene and plenty of bird song in its environment but without the hormonal signaling associated with seasonal song in males will not produce the song at all.

So, what does this research tell us about the way in which FOXP2 affects song development in song birds? The affected area of the brain is known as Area X. Here, there is a kind of neuron called the "spiny neuron." This is a type of neuron found, for instance, in the mammalian basal ganglia and Area X of song birds. They have extensive dendritic trees (dendrites are input areas of a neuron), with zillions of "spines," all of which receive inputs from other neurons. In turn, each neuron projects to (connects to and affects) other neurons that they tend to inhibit. Thus, spiny neurons are a class of neurons that are considered inhibitory.

In birds, these neurons process sound and are active during singing. They play a role in tuning the motor output related to song in relation to what is heard. In essence, under certain conditions (being the right sex, it being the right time of year, there being song in the auditory environment) these neurons assist in the refining of song, indeed, the actual process of learning song. The observation that FOXP2 expression is increased during song learning suggests that this gene is functionally related to the process of song learning.

FoxP2 might mediate adaptive structural and functional changes of the spiny neurons while the song is learned. During the seasonal phase of vocal plasticity in canaries, increased FoxP2 expression in the fall months might similarly be involved in seasonal song modifications. Since FoxP2 is a transcription factor, it could act by positively or negatively regulating plasticity-related genes. If FoxP2 functions as a plasticity-promoting factor, knockdown pupils should have been less plastic during learning, resulting in impoverished imitation and abnormally invariant song.

The experimental birds with FOXP2 knockdown drop syllables but they also have more variable syllables, which suggests that a different effect is happening. In other words, one model suggests that FOXP2 deficient cells should lead to more variable syllables, but another model suggests that it should lead to less variable syllables.

The reason for this is most likely that FOXP2, as a regulatory gene, affects more than one system "downstream" in the process. The details of this are yet to be worked out, but now that there is an animal model for studying this, understanding this system is likely not too far in the future.

The identification of the downstream target genes of FoxP2 and the electrophysiological characterization of spiny neurons with reduced FoxP2 levels will shed light on the mechanisms by which FoxP2 affects the outcome of vocal learning.

How does this related to the human case, of individuals with a broken FOXP2 gene having certain speech abnormalities?

The human core deficit affects the production of rapid, sequential mouth movements, which are required for speech articulation [43], and is thought to be caused by erroneous brain development. Perhaps the speech impairment results from a problem with motor learning rather than motor performance during speech learning, a hypothesis that is in line with recent theories on basal ganglia dysfunction in various developmental disorders

HAESLER, S.et. al. (2007): Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X. PLoS Biology, 5:12, e321 doi:10.1371/journal.pbio.0050321.