Reelin signaling in the basal ganglia: comparative neuroanatomy and implications for vocal behavior
Vocal learning is a complex motor activity that relies on the coordination of different brain regions including the basal ganglia. By studying the vocal learning zebra finch, this work has uncovered a novel pathway that is regulated by singing behavior. The Reelin-signaling pathway like the human language transcription factor, FoxP2, is regulated in a basal ganglia region, Area X. The pathway was found to be regulated during the sensorimotor phase of song learning in finches as well as in adults. Injections of recombinant Reelin into Area X during sensorimotor learning showed that Reelin injected pupils to learn their tutors’ songs better than controls. These results indicated that 1) Reelin signaling is important to sensorimotor learning phase of vocal learning 2) Like FoxP2, oscillations of the level of Reelin signaling are likely to subserve vocal learning. This pathway is implicated in the etiology of autism spectrum disorders (ASD), of which social communication deficits are key diagnostic criteria. Mice insufficient or completely lacking Reelin signaling components (Dab1, Apoer2, and Vldlr) exhibited reduced number of vocalizations and abnormal vocalization repertoires. Reelin-secreting cell types and Reelin-sensitive cell types were identified across both mouse and zebra finch species. A common theme was uncovered, whereby Reelin is secreted in the striatum, and Dab1 is expressed in the pallidum. I therefore hypothesize that Reelin signaling occurs in the basal ganglia in a striato-pallidal manner across different species and may reflect a general mechanism of signaling in the basal ganglia. Some features of Reelin signaling that are unique to the zebra finch Area X were uncovered including: Reelin secretion by calretinin and somatostatin interneurons. Additionally, Dab1 expression was observed in cholinergic interneurons of Area X. Contrasts between the zebra finch and mouse highlight differences that could a result of unique qualities of Area X or could reflect differences between vocal leaning and non-vocal learning basal ganglia. This work identifies, confirms, and defines the novel involvement of an established pathway, the Reelin-signaling pathway, in vocal behavior of multiple species.