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Are Synaptic Clefts Directionally Oriented?
Biorxiv : the Preprint Server for Biology
|February 12, 2026
Summary
Synaptic clefts in the brain are not randomly oriented but show directional biases. This previously unrecognized mesoscale anisotropy impacts cortical organization and connectivity across species.
Area of Science:
- Neuroscience
- Computational Neuroscience
- Connectomics
Background:
- Synapses are key components of cortical circuits.
- Their geometry is traditionally viewed as a local, isotropic property.
- The assumption of random synaptic cleft orientation is widespread.
Purpose of the Study:
- To investigate the spatial orientation of synaptic clefts.
- To determine if synaptic geometry exhibits mesoscale architectural properties.
- To test the prevailing assumption of isotropic synaptic cleft orientation.
Main Methods:
- Analysis of approximately 117 million synaptic clefts.
- Utilized two large-scale electron microscopy datasets (human H01 and mouse MICrONS).
- Statistical analysis of orientation distributions across cortical layers.
Main Results:
- Synaptic cleft orientations are not random but exhibit statistically significant directional biases.
- These biases are spatially coherent across cortical layers.
- Mesoscale anisotropy is conserved across species (human and mouse), but stronger in human association cortex.
Conclusions:
- Synaptic geometry possesses a mesoscale anisotropy, challenging the isotropic assumption.
- This anisotropy represents an unrecognized dimension of cortical microarchitecture.
- Synaptic geometry likely influences circuit organization, mesoscale connectivity, and neural interactions with electric fields.
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