Beyond Critical Period Learning: Striatal FoxP2 Affects the Active Maintenance of Learned Vocalizations in Adulthood

Abstract

In humans, mutations in the transcription factor forkhead box P2 (FOXP2) result in language disorders associated with altered striatal structure. Like speech, birdsong is learned through social interactions during maturational critical periods, and it relies on auditory feedback during initial learning and on-going maintenance. Hearing loss causes learned vocalizations to deteriorate in adult humans and songbirds. In the adult songbird brain, most FoxP2-enriched regions (e.g., cortex, thalamus) show a static expression level, but in the striatal song control nucleus, area X, FoxP2 is regulated by singing and social context: when juveniles and adults sing alone, its levels drop, and songs are more variable. When males sing to females, FoxP2 levels remain high, and songs are relatively stable: this “on-line” regulation implicates FoxP2 in ongoing vocal processes, but its role in the auditory-based maintenance of learned vocalization has not been examined. To test this, we overexpressed FoxP2 in both hearing and deafened adult zebra finches and assessed effects on song sung alone versus songs directed to females. In intact birds singing alone, no changes were detected between songs of males expressing FoxP2 or a GFP construct in area X, consistent with the marked stability of mature song in this species. In contrast, songs of males overexpressing FoxP2 became more variable and were less preferable to females, unlike responses to songs of GFP-expressing control males. In deafened birds, song deteriorated more rapidly following FoxP2 overexpression relative to GFP controls. Together, these experiments suggest that behavior-driven FoxP2 expression and auditory feedback interact to precisely maintain learned vocalizations.

FOXP transcription factors in vertebrate brain development, function, and disorders

“…This behavior change is accompanied by decreased dopamine D1 receptor and DARPP-32 expression in Area X, similar to the Drd1 and Ppp1r1b downregulation in Foxp2 cKO mouse cortex (Co et al, 2019;Murugan et al, 2013). FoxP2 overexpression in adult Area X does not affect vocal variability, but upon deafening, overexpression hastens song deterioration and alters song variability, indicating a role for FoxP2 in maintaining song stability (Day, Hobbs, Heston, & White, 2019).…”

Dynamic FoxP2 levels in male zebra finches are linked to morphology of adult-born Area X medium spiny neurons

“…The core-phenotype of DVD consists of altered precision, consistency and sequencing of movements underlying speech in the absence of neuromuscular deficits 11 . In addition, altered FoxP2 levels in adult Area X affect the dopaminergic modulation of corticostriatal signaling important to song variability and affect song maintenance 12,13 , stressing the fact that tight regulation of FoxP2 expression is a prerequisite for correct neural transmission in differentiated neural circuits. Additional effects of Foxp2 and its disruption on the embryonic development and the function of neural circuits have been described in mice [14][15][16][17][18][19][20][21][22][23] .…”

Identification of FoxP circuits involved in locomotion and object fixation in Drosophila

“…At least for these tasks in mammals, a FoxP family member does serve a postnatal function that is independent of brain development (brain morphology was unaltered in these experiments). Also in birds, evidence has been accumulating that adult FoxP expression serves a song plasticity function [101][102][103][104][105][106].…”