Functional Divergence of Axon-Carrying Dendrite (AcD) and NonAcD Cells in Learning and Stability

Axon-carrying dendrite (AcD) cells are a specialized class of hippocampal neurons where the axon initial segment originates from a basal dendrite rather than the soma, creating a privileged pathway for excitatory inputs on AcD branches to bypass perisomatic inhibition. However, their functional role in learning and synaptic stability remains unclear. To address this question, we modeled a CA3-CA1 network to compare the learning dynamics and synaptic stability of AcD and nonAcD cells. The results revealed that, during learning, these cell types employ distinct mechanisms. AcD cells primarily adopt a single-modal strategy, with all dendritic branches converging to encode inputs from a single assembly, whereas nonAcD cells follow a multi-modal approach, with individual branches encoding inputs from distinct assemblies. Additionally, consistent with experimental findings, our results suggest that during periods of high inhibition (such as ripples), AcD cells maintain stable synaptic weights, unlike the synaptic decay observed in nonAcD cells. These results, in line with experimental evidence, suggest that although the morphological distinction between AcD and nonAcD cells was long overlooked, it proves to be important, as it results in functional differences in learning mechanisms and in the capacity for stable information storage, highlighting their key role in learning and memory consolidation.