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Unsupervised classification of brain-wide axons reveals the presubiculum neuronal projection blueprint

Diek W. Wheeler (), Shaina Banduri, Sruthi Sankararaman, Samhita Vinay and Giorgio A. Ascoli ()
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Diek W. Wheeler: George Mason University
Shaina Banduri: George Mason University
Sruthi Sankararaman: George Mason University
Samhita Vinay: George Mason University
Giorgio A. Ascoli: George Mason University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract We present a quantitative strategy to identify all projection neuron types from a given region with statistically different patterns of anatomical targeting. We first validate the technique with mouse primary motor cortex layer 6 data, yielding two clusters consistent with cortico-thalamic and intra-telencephalic neurons. We next analyze the presubiculum, a less-explored region, identifying five classes of projecting neurons with unique patterns of divergence, convergence, and specificity. We report several findings: individual classes target multiple subregions along defined functions; all hypothalamic regions are exclusively targeted by the same class also invading midbrain and agranular retrosplenial cortex; Cornu Ammonis receives input from a single class of presubicular axons also projecting to granular retrosplenial cortex; path distances from the presubiculum to the same targets differ significantly between classes, as do the path distances to distinct targets within most classes; the identified classes have highly non-uniform abundances; and presubicular somata are topographically segregated among classes. This study thus demonstrates that statistically distinct projections shed light on the functional organization of their circuit.

Date: 2024
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DOI: 10.1038/s41467-024-45741-x

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