Disinhibition enables vocal repertoire expansion after a critical period

ABSTRACT The efficiency of motor skill acquisition is age-dependent, making it increasingly challenging to learn complex maneuvers later in life 1–6 . Zebra finches, for instance, acquire a complex vocal motor program during a developmental critical period 7,8 after which the learned song is essentially impervious to modification 9 . Although inhibitory interneurons are implicated in critical period closure 10–13 , it is unclear whether manipulating them can reopen heightened motor plasticity windows. Using pharmacology and a novel cell-type specific optogenetic approach, we manipulated inhibitory neuron activity in a premotor area of adult zebra finches beyond their critical period. When exposed to auditory stimulation in the form of novel song, manipulated birds added new vocal syllables to their stable song sequence. By lifting inhibition in a premotor area during sensory experience, we reintroduced vocal plasticity, promoting an expansion of the syllable repertoire without compromising pre-existing song production. Our findings provide insights into motor skill learning capacities, offer potential for motor recovery after injury, and suggest avenues for treating neurodevelopmental disorders involving inhibitory dysfunctions.