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Sublayer-specific microcircuits of corticospinal and corticostriatal neurons in motor cortex

Abstract

The mammalian motor system is organized around distinct subcortical subsystems, suggesting that the intracortical circuits immediately upstream of spinal cord and basal ganglia might be functionally differentiated as well. We found that the main excitatory pathway in mouse motor cortex, layer 2/3→5, is fractionated into distinct pathways targeting corticospinal and corticostriatal neurons, which are involved in motor control. However, connections were selective for neurons in certain sublayers: corticospinal neurons in upper layer 5B and corticostriatal neurons in lower 5A. A simple structural combinatorial principle accounts for this highly specific functional circuit architecture: potential connectivity is established by neuronal sublayer positioning and actual connectivity in this framework is determined by long-range axonal projection targets. Thus, intracortical circuits of these pyramidal neurons are specified not only by their long-range axonal targets or their layer or sublayer positions, but by both, in specific combinations.

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Figure 1: Sublayer-specific circuits of corticospinal projection neurons.
Figure 2: Sublayer-specific circuits of crossed corticostriatal projection neurons.
Figure 3: Layer 2/3→5 pathways project to the layer 5A/B border.
Figure 4: CRACM analysis of the sublayer specificity of crossed corticostriatal neurons, circuits showing that layer 2/3 axons provide input to layer 5A, but not layer 5B, corticostriatal neurons.
Figure 5: Pair-mapping analysis of the projection-class specificity of circuits in the same sublayer showing that layer 2/3 axons avoid layer 5B corticostriatal neurons in favor of corticospinal neurons.
Figure 6: Input patterns for ipsilaterally projecting corticostriatal neurons showing that the majority have the same circuit phenotype observed for the crossed corticostriatal neurons.
Figure 7: Laminar connectivity matrix analysis showing partial segregation of L2/3 inputs to corticostriatal and corticospinal neurons.

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Acknowledgements

We thank L. Petreanu and K. Svoboda (Howard Hughes Medical Institute) for plasmids and comments, and D. Buxton for advice on retrograde labeling methods. The work was funded by grants from the Whitehall Foundation and the National Institute of Neurological Disorders and Stroke at the US National Institutes of Health (NS061963).

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All of the authors participated in designing, conducting and analyzing the experiments. P.L.S. performed most of the corticospinal recordings and C.T.A. performed most of the corticostriatal recordings. T.K. carried out the flavoprotein autofluorescence imaging. G.M.G.S., C.T.A. and P.L.S. wrote the paper.

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Correspondence to Gordon M G Shepherd.

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The authors declare no competing financial interests.

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Anderson, C., Sheets, P., Kiritani, T. et al. Sublayer-specific microcircuits of corticospinal and corticostriatal neurons in motor cortex. Nat Neurosci 13, 739–744 (2010). https://doi.org/10.1038/nn.2538

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