Neuronal processing is classically divided into dendritic input, somatic integration and axonal output. In this scheme, the axon initial segment (AIS) is usually located immediately adjacent to the cell soma. Here we report an unusual location of AIS at basal dendrites of murine hippocampal CA1 pyramidal neurons which may cause asymmetric input processing. Cell morphology was visualized by expression of DsRed in a subset of neurons (Brainbow 2.0 line O; Livet et al, 2007). The AIS was identified by immunostaining against ankyrin-G or ß4-spectrin. Quantitative analysis revealed that the axon originated from basal dendrites instead of the soma in about 50% of cells. The highest prevalence of axon-carrying dendrites was found in the middle portion of CA1, with fewer axon-carrying dendrites in CA3 or the subiculum. Electrical properties of these cells and fine structure of the axon initial segment (AIS) were not modified by axonal location, implying the AIS as site of action potential generation is maintained. However, computer simulations suggested that the axon-carrying basal dendrite is functionally privileged: so action potential threshold is reached more easily upon depolarization of this dendrite. Multiphoton glutamate uncaging confirmed that basal dendrites which carry the axon were indeed more likely to trigger action potentials and to exhibit dendritic spikes than “normal” dendrites.

Taken together, our data reveal a surprisingly frequent dendritic origin of axons of CA1 pyramidal neurons and a privileged synaptic input onto these dendrites. This morphological feature might define a neuronal subpopulation with special functional properties in signal integration and assembly formation.

Supported by the German Ministry of Education and Research (BMBF, 01GQ1003A, BCCN Heidelberg-Mannheim).