Enhancing cortico-motoneuronal projections for vocalization in mice

Several hypotheses have been proposed on the anatomical brain differences that endow some species with the rare ability of vocal learning, a critical component of spoken language. One long-standing thus far untested hypothesis is that a robust direct projection from motor cortex layer 5 neurons to brainstem vocal motor neurons enables fine motor control of laryngeal musculature in vocal learners. This connection has been proposed to form from specialized expression of axon guidance genes in human speech layer 5 neurons and the equivalent songbird neurons of the robust nucleus of the arcopallium. Here we generated mice with conditional knockdown of an axon-guidance receptor, PLXNA1, in motor cortex layer 5 neurons, to recapitulate the human and songbird brain expression patterns. These mice showed enhanced layer 5 cortical projections to brainstem vocal motor neurons, increased functional connectivity to phonatory muscles, and displayed a wider range of vocal abilities depending on developmental and social contexts. Our findings are consistent with the theory that direct vocal cortico-motoneuronal projections influence vocal behaviors.