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bioRxiv · 10.1101/2025.10.25.684569

The songbird basal ganglia connectome

Rother, A.·Januszewski, M.·Jain, V.·Fee, M. S.·Kornfeld, J. M. R.
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Abstract

The basal ganglia (BG) play an essential role in shaping vertebrate behavior, ranging from motor learning to emotions, but comprehensive maps of their canonical synaptic architecture are missing. In mammals, three main neuronal pathways through the BG have been described - the direct, indirect, and hyperdirect pathways - which together orchestrate many aspects of learning and behavior. In songbirds, cell types associated with striatal and pallidal components appear intermingled in a single basal ganglia nucleus, Area X, essential for song learning. This allows for the dense reconstruction of the entire circuit within a compact volume. Here, we introduce the first vertebrate basal ganglia connectome, comprising over 8,500 automated neuron reconstructions connected by about 20 million synapses. High image quality and automated reconstruction allowed analysis with minimal manual proofreading. Based on direct anatomical measurement of synaptic connectivity, we confirm that a direct, indirect and hyperdirect pathway can be traced through Area X. However, detailed morphological and connectomic analysis revealed no clearly distinct direct and indirect medium spiny neuron subpopulations, and a dominance of the direct and hyperdirect pathway. In addition to previously identified neuron types in Area X, we could distinguish three novel GABAergic neuron types, two of which are major output targets of GPe neurons, leading to novel feedback circuitry within Area X. We further found unexpectedly strong neuronal interconnectivity and recurrency between neurons associated with all pathways. Our data thus challenge the universality of the view of the basal ganglia as an information processor organized into discrete feedforward pathways.

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Rother, A., Januszewski, M., Jain, V., Fee, M. S., Kornfeld, J. M. R.. 2025-10-27. The songbird basal ganglia connectome. https://doi.org/10.1101/2025.10.25.684569

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