Songbird mesostriatal dopamine pathways are spatially segregated before the onset of vocal learning

Abstract

Diverse dopamine (DA) pathways send distinct reinforcement signals to different striatal regions. In adult songbirds, a DA pathway from the ventral tegmental area (VTA) to Area X, the striatal nucleus of the song system, carries singing-related performance error signals important for learning. Meanwhile, a parallel DA pathway to a medial striatal area (MST) arises from a distinct group of neighboring DA neurons that lack connectivity to song circuits and do not encode song error. To test if the structural and functional segregation of these two pathways depends on singing experience, we carried out anatomical studies early in development before the onset of song learning. We find that distinct VTA neurons project to either Area X or MST in juvenile birds before the onset of substantial vocal practice. Quantitative comparisons of early juveniles (30-35 days post hatch), late juveniles (60-65 dph), and adult (>90 dph) brains revealed an outsized expansion of Area X-projecting neurons relative to MST-projecting neurons in VTA over development. These results show that a mesostriatal DA system dedicated to social communication can exist and be spatially segregated before the onset of vocal practice and associated sensorimotor experience.

Fig 1. VTA projections to MST or Area X are segregated before the onset of vocal practice.

(A) Schematic of the experimental strategy used to label VTA projections to MST and Area X; (B) Darkfield image with expanded view of VTA, denoted by dashed white rectangle, scale bar 250 μm; (C) MST (magenta) and Area X (orange) projecting neurons in VTA in adults. Right to left: examples of a similar region in VTA from three different birds. Scale bar, 75 um. Dorsal is up; anterior is to the right. (D) Same as C except for late juveniles 60–65 dph; (E) Same as C except for early juveniles 30–35 dph. (F) Average cell counts per hemisphere of populations projecting to Area X (dark gray) and MST (white) from VTA in all three injection sites with an n of 12, 7, and 7 hemispheres respectively. Asterisks above vertical error bars for the late juveniles and adult populations show results of Tukey’s post-hoc analysis when comparing to appropriate early juvenile populations. Asterisks above horizontal brackets show results of Welch two sample t-tests between neuron populations within the same age group. (G) Percent of co-labeled cells in VTA that project to both MST and Area X in all three injection sites with an n of 12, 7, and 7 hemispheres respectively. (H) Proportion of Area X (black) and MST (gray) projecting cells over total labeled cells in the brain slice, progressing from medial to lateral. Error bars reflect standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001. NS, not significant.