DifferentialFoxP2andFoxP1expression in a vocal learning nucleus of the developing budgerigar

Abstract

The forkhead domain FOXP2 and FOXP1 transcription factors are implicated in several cognitive disorders with language deficits, notably autism, and thus play a central role in learned vocal motor behavior in humans. Although a similar role for FoxP2 and FoxP1 is proposed for other vertebrate species, including songbirds, the neurodevelopmental expression of these genes are unknown in a species with lifelong vocal learning abilities. Like humans, budgerigars (Melopsittacus undulatus) learn new vocalizations throughout their entire lifetime. Like songbirds, budgerigars have distinct brain nuclei for vocal learning, which include the magnocellular nucleus of the medial striatum (MMSt), a basal ganglia region that is considered developmentally and functionally analogous to Area X in songbirds. Here we used in situ hybridization and immunohistochemistry to investigate FoxP2 and FoxP1 expression in the MMSt of juvenile and adult budgerigars. We found FoxP2 mRNA and protein expression levels in the MMSt that were lower than the surrounding striatum throughout development and adulthood. In contrast, FoxP1 mRNA and protein had an elevated MMSt/striatum expression ratio as birds matured, regardless of their sex. These results show that life-long vocal plasticity in budgerigars is associated with persistent low-level FoxP2 expression in the budgerigar MMSt, and suggests the possibility that FoxP1 plays an organizational role in the neurodevelopment of vocal motor circuitry. Thus, developmental regulation of the FoxP2 and FoxP1 genes in the basal ganglia appears essential for vocal mimicry in a range of species that possess this relatively rare trait.

Core and Shell Song Systems Unique to the Parrot Brain

“…The FOXP1 transcription factor, a co-factor of FOXP2 that is required for speech and song acquisition in humans and songbirds [ 53 ], was reported to be differentially expressed in the NLC analog of vocal learners [ 35 , 54 ]; we found here that it is expressed in a gradient of higher to lower expression from the NLC core to the shell, but only for the part of the shell that corresponds to the vocalizing-driven song nucleus (Fig 7c and 7d ). Interestingly, FOXP1 has a ring of lower expression around the MMSt song nucleus, but this is thought to be a non-vocal motor part of the striatum around MMSt [ 35 , 55 ]. NR2A glutamate receptor upregulation (Fig 8a and 8b ) and GLUR1 downregulation in NLC [ 56 ] (Fig 8c and 8d ) corresponds to our PVALB -defined NLC core.…”

Understanding Language from a Genomic Perspective

“…Although zebra finch vocal learning is restricted to juveniles, species like the budgerigar exhibit vocal plasticity in adulthood. In adult male budgerigars, FoxP2 levels within the striatal song nucleus (equivalent to Area X) are relatively low and are not modulated by singing, whether or not the song is directed to a female (62,197).…”

Social calls provide novel insights into the evolution of vocal learning

“…These similarities in brain mechanisms have helped propel research on song learning in birds. While fewer studies have examined mechanisms of call learning, there is evidence that some key genes, particularly FoxP2 , play similar roles in promoting song and call learning in birds (Hara et al, 2015; Whitney et al, 2015). Moreover, there is evidence that the song control pathway in the brain, which controls song production, also controls the vocal production of unlearned calls (Ter Maat et al, 2014), although, to our knowledge, no studies have yet examined the role of these regions in the production of learned calls in species that learn both calls and song.…”