Hemispheric asymmetry of calbindin-positive neurons is associated with successful song imitation

•Density of neuronal cell types (CB+/PV+/CT+) differs in young zebra finches.•Good learners exhibit hemispheric asymmetry of CB+ neurons in auditory regions.•Fewer CB+ neurons in left auditory cortex correlates with successful song learning. The plasticity that facilitates learning during critical (sensitive) periods in development is tightly regulated by inhibitory neurons. Song acquisition in birds is one example of a learning process that occurs during a sensitive period early in development. Sensory experience with a song ‘tutor’ during this sensitive period prunes excitatory and inhibitory synapses in the song production nucleus HVC (proper noun). Neurons in the caudomedial nidopallium (NCM), a secondary auditory region, lose their tutor song selectivity when gamma-aminobutyric acid (GABA) signaling is blocked. Given the importance of inhibition in the song learning process, we investigated whether individual differences in learning outcomes can be explained by the distribution of specific populations of (mostly) inhibitory neurons in HVC and NCM. We measured the densities of distinct neuronal populations (defined by their expression of the calcium-binding proteins calbindin, calretinin, and parvalbumin) in these two regions. We found that lateralization of calbindin-positive neurons was related to successful song learning: good learners were characterized by hemispheric asymmetry of calbindin-positive neurons in the medial NCM (fewer CB+ neurons in the left hemisphere), whereas poor learners did not show any asymmetry. In contrast, the density of all three neuronal populations in HVC did not differ between good and poor learners. These findings not only identify a specific (presumably) inhibitory cell type (calbindin-expressing neurons) that is related to song learning, but also emphasize the role of hemispheric asymmetry in auditory memory formation.