Axon-Carrying Dendrites Convey Privileged Synaptic Input in Hippocampal Neurons

Neuronal processing is classically conceptualized as dendritic input, somatic integration, and axonal output. The axon initial segment, the proposed site of action potential generation, usually emanates directly from the soma. However, we found that axons of hippocampal pyramidal cells frequently derive from a basal dendrite rather than from the soma. This morphology is particularly enriched in central CA1, the principal hippocampal output area. Multiphoton glutamate uncaging revealed that input onto the axon-carrying dendrites (AcDs) was more efficient in eliciting action potential output than input onto regular basal dendrites. First, synaptic input onto AcDs generates action potentials with lower activation thresholds compared with regular dendrites. Second, AcDs are intrinsically more excitable, generating dendritic spikes with higher probability and greater strength. Thus, axon-carrying dendrites constitute a privileged channel for excitatory synaptic input in a subset of cortical pyramidal cells. [Display omitted] •Axons derive from a dendrite in a large proportion of hippocampal pyramidal neurons•Axon-carrying dendrites have higher propensity to generate dendritic spikes•Input to axon-carrying dendrites elicits action potentials with lower threshold•Structure of hippocampal principal neurons mediates asymmetric input processing Thome et al. find that axons of hippocampal pyramidal cells frequently derive from a basal dendrite rather than from the soma. These dendrites constitute a privileged channel for excitatory synaptic input, generating a major functional asymmetry in a subset of cortical neurons.