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bioRxiv · 10.64898/2026.01.27.702163

Hippocampal Projections to the Striatal Compartments, Striosome and Matrix, are Spatially Segregated in CA1

Tieu, A. N.·Sadi, A.·Waugh, J. L.
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Abstract

The hippocampus routes information to the striatum through at least four polysynaptic circuits. Striatal projection neurons are organized into two tissue compartments, the matrix and striosome, which differ in their embryologic origins, relative abundance, intra-striate location, and afferent and efferent connectivity. These compartments are embedded in distinct functional networks and are activated by different tasks. Consequently, hippocampal inputs that route preferentially through the striosome may underpin different functions and engage with different remote networks than inputs that route through the matrix. It was unknown whether striosome-bound and matrix-bound projections from the hippocampus followed different polysynaptic circuits. We assessed hippocampo-striate projections in living humans using probabilistic diffusion tractography by first parcellating the striatum into voxels with striosome-like and matrix-like structural connectivity. We then quantified structural connectivity between hippocampal efferents (CA1) to each set of compartment-like voxels. CA1 projections to striosome-like voxels in the dorsal striatum (caudate and putamen) were 3.1-fold more abundant than those to matrix-like voxels, particularly in caudo-lateral CA1. This striosome-favoring bias was similar in three segregated hippocampo-striate circuits, in streamlines routing through the subiculum, lateral septum, or medial prefrontal cortex. However, a small region in rostro-medial CA1 preferentially targeted matrix-like voxels. Functional connectivity between CA1 and compartment-like voxels matched this segregated pattern: CA1 activation was correlated with striosome-like voxels but anti-correlated with matrix-like voxels. Additionally, streamlines from CA1 to nucleus accumbens exhibited hemispheric asymmetries, with the left hemisphere biased towards matrix and the right towards striosome. These findings suggest that hippocampo-striate projections are spatially segregated into compartment-specific circuits.

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Tieu, A. N., Sadi, A., Waugh, J. L.. 2026-01-30. Hippocampal Projections to the Striatal Compartments, Striosome and Matrix, are Spatially Segregated in CA1. https://doi.org/10.64898/2026.01.27.702163

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