Divergent hippocampal output via covariant local and long-range neuronal structure

Understanding the brain’s structural architecture and organizational logic is essential for interpreting brain function. Morphological properties are well-known to discretely separate distinct types of cells and influence their respective computations, but whether finer-scale morphological differences within narrowly-defined cell types can govern disparate computations remains unknown. Here, we address this question by focusing on long-range projection neurons of the subiculum, the primary output cells of the hippocampus. We used high-resolution whole-brain neuronal reconstructions to concomitantly examine local and long-range neuronal architecture, as well as computational modeling to identify how projection-specific morphology shapes circuit computation. Our results reveal that subiculum projection neurons have a high degree of "matched complexity" between dendritic and axonal patterning, and that this dendritic-axonal covariation can lead to projection-specific input-output operations. Extending this work with viral circuit tracing, we further illustrate that subiculum neurons embedded within different long-range circuits exhibit spatially distinct local dendritic domains, suggesting these projection streams also receive fundamentally distinct types of input. This covariance of single-cell dendritic morphology with long-range neural targets illustrates a new form of organizational logic for hippocampal circuits, and likely plays a key role in driving distinct computations across hippocampal output pathways. • Analysis of whole-brain subiculum dendritic and axonal neuronal reconstructions • Subiculum projection neurons exhibit interrelated dendritic and axonal subtypes • Dendrites and axons of subiculum neurons covary in complexity • Projection-defined subiculum subtypes have distinct dendritic domains