Integrative analysis of single-neuron projectomes links connectome, transcriptome, and function in the mouse cortex

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• The mammalian cortex's complex neural network underlies sensory processing, motor control, and cognition.
• Principles of single-neuron connectivity, transcriptome, and activity remain poorly understood.

Purpose of the Study:

• To reconstruct the projectomes of approximately 20,000 neurons in the entire mouse cortex.
• To identify projection-defined neuronal subtypes and their distributions.
• To analyze cortico-cortical and cortico-subcortical connectivity patterns.

Main Methods:

• Reconstruction of neuronal projectomes using advanced tracing techniques.
• Identification and classification of 346 projection-defined neuronal subtypes.
• Analysis of connectivity modules, cortical hierarchy, and topographic maps.

Main Results:

• Discovery of 346 region- and layer-specific projection-defined neuronal subtypes.
• Unveiling of seven cortico-cortical modules with submodular organization and a high-resolution cortical hierarchy.
• Detailed mapping of cortico-subcortical projections, including novel cortico-basal ganglia pathways.
• Demonstration of close correlations between connectivity maps, Ca2+ activity, electrical activity, and gene expression.

Conclusions:

• The study provides a foundational, fine-grained map of the mouse cortical connectome.
• This multimodal analysis links neuronal structure, activity, and gene expression.
• The findings offer a new framework for understanding cortical network organization and function.