Abstract
The principles that govern where excitatory synapses form on cortical pyramidal neurons remain unclear. A long-standing hypothesis is that connectivity mirrors neuronal geometry—with apical dendrites dominating in layer 1 and basal dendrites in deeper layers. Leveraging the MiCRONS cubic-millimetre serial electron-microscopy dataset ([1, 2]), we mapped 4968 synapses onto reconstructed apical and basal arbors across layers 1–6 of mouse visual cortex. Contrary to a simple gradient model, synaptic targeting is overwhelmingly biased toward basal dendrites in layers 2/3–6, even where apical shafts are abundant. Layer 1 is the sole exception, exhibiting the expected apical bias. Basal predominance scales with local soma density and the relative arbor length available for contact, such that 66% (61101/92445) of all synapses land within 130 µm of the soma, placing most excitatory drive near the cell body. Axonal analysis revealed specificity beyond mere geometric opportunity: individual axon segments preferentially innervated either basal or apical compartments far more often than predicted by chance, indicating compartment-selective wiring rules. Together, our results show that cortical connectivity is shaped by both neuronal geometry and axon-level targeting preferences, redefining how pyramidal cells integrate information across layers and apical and basal dendrites.
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Abstract
The principles that govern where excitatory synapses form on cortical pyramidal neurons remain unclear. A long-standing hypothesis is that connectivity mirrors neuronal geometry—with apical dendrites dominating in layer 1 and basal dendrites in deeper layers. Leveraging the MiCRONS cubic-millimetre serial electron-microscopy dataset ([1, 2]), we mapped 4968 synapses onto reconstructed apical and basal arbors across layers 1–6 of mouse visual cortex. Contrary to a simple gradient model, synaptic targeting is overwhelmingly biased toward basal dendrites in layers 2/3–6, even where apical shafts are abundant. Layer 1 is the sole exception, exhibiting the expected apical bias. Basal predominance scales with local soma density and the relative arbor length available for contact, such that 66% (61101/92445) of all synapses land within 130 µm of the soma, placing most excitatory drive near the cell body. Axonal analysis revealed specificity beyond mere geometric opportunity: individual axon segments preferentially innervated either basal or apical compartments far more often than predicted by chance, indicating compartment-selective wiring rules. Together, our results show that cortical connectivity is shaped by both neuronal geometry and axon-level targeting preferences, redefining how pyramidal cells integrate information across layers and apical and basal dendrites.
Competing Interest Statement
The authors have declared no competing interest.
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