Dynamic Expression of Cadherins Regulates Vocal Development in a Songbird

BACKGROUND: Since, similarly to humans, songbirds learn their vocalization through imitation during their juvenile stage, they have often been used as model animals to study the mechanisms of human verbal learning. Numerous anatomical and physiological studies have suggested that songbirds have a neural network called ‘song system’ specialized for vocal learning and production in their brain. However, it still remains unknown what molecular mechanisms regulate their vocal development. It has been suggested that type-II cadherins are involved in synapse formation and function. Previously, we found that type-II cadherin expressions are switched in the robust nucleus of arcopallium from cadherin-7-positive to cadherin-6B-positive during the phase from sensory to sensorimotor learning stage in a songbird, the Bengalese finch. Furthermore, in vitro analysis using cultured rat hippocampal neurons revealed that cadherin-6B enhanced and cadherin-7 suppressed the frequency of miniature excitatory postsynaptic currents via regulating dendritic spine morphology. METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of cadherins in vocal development, we performed an in vivo behavioral analysis of cadherin function with lentiviral vectors. Overexpression of cadherin-7 in the juvenile and the adult stages resulted in severe defects in vocal production. In both cases, harmonic sounds typically seen in the adult Bengalese finch songs were particularly affected. CONCLUSIONS/SIGNIFICANCE: Our results suggest that cadherins control vocal production, particularly harmonic sounds, probably by modulating neuronal morphology of the RA nucleus. It appears that the switching of cadherin expressions from sensory to sensorimotor learning stage enhances vocal production ability to make various types of vocalization that is essential for sensorimotor learning in a trial and error manner.