Abstract

Simple SummaryMagnetic resonance imaging showed that striatal injury leads to structural changes within several brain areas. Here, we specify these changes via gene expression of synaptic plasticity markers, neuronal markers, assessing the number of newborn cells as well as cell densities. We found that the injury resulted in long-lasting modifications involving plasticity and neural protection mechanisms in areas directly as well as indirectly connected with the damaged striatum, including the cerebellum.The striatal region Area X plays an important role during song learning, sequencing, and variability in songbirds. A previous study revealed that neurotoxic damage within Area X results in micro and macrostructural changes across the entire brain, including the downstream dorsal thalamus and both the upstream pallial nucleus HVC (proper name) and the deep cerebellar nuclei (DCN). Here, we specify these changes on cellular and gene expression levels. We found decreased cell density in the thalamic and cerebellar areas and HVC, but it was not related to neuronal loss. On the contrary, perineuronal nets (PNNs) in HVC increased for up to 2 months post-lesion, suggesting their protecting role. The synaptic plasticity marker Forkhead box protein P2 (FoxP2) showed a bi-phasic increase at 8 days and 3 months post-lesion, indicating a massive synaptic rebuilding. The later increase in HVC was associated with the increased number of new neurons. These data suggest that the damage in the striatal vocal nucleus induces cellular and gene expression alterations in both the efferent and afferent destinations. These changes may be long-lasting and involve plasticity and neural protection mechanisms in the areas directly connected to the injury site and also to distant areas, such as the cerebellum.

Highlights

  • The song control system (SCS) in songbird forms pathways necessary for learning, production, and perception of learned vocalization [1–7]

  • We focused on the expression of Forkhead box protein P2 (FoxP2), perineuronal nets (PNNs), and PV, but we examined the incorporation of newborn cells

  • Area X Lesion Leads to a Temporary Decrease in the Number of Cells in HVC, dorsolateral nucleus of medial thalamus (DLM), and deep cerebellar nuclei (DCN)

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Summary

Introduction

The song control system (SCS) in songbird forms pathways necessary for learning, production, and perception of learned vocalization [1–7]. The AFP in the songbirds includes the pallio-basal ganglia-thalamo-pallial loop and connects the pallial nucleus HVC (proper name) to the striatal nucleus Area X to the dorsolateral nucleus of medial thalamus (DLM) to the robust nucleus of the arcopallium (RA) (Figure 1a). This loop has been compared to the mammalian premotor cortico-basal ganglia-thalamo-cortical loops [12,13]. The involvement of the cerebellum in language was first noticed in humans with speech deficits in 1917 ([16] reviewed in [17,18]), but it has not been traditionally associated with learned song production in songbirds.

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