The prosubiculum in the human hippocampus: A rostrocaudal, feature-driven, and systematic approach

The hippocampal subfield prosubiculum (ProS), is a conserved neuroanatomic region in mouse, monkey, and human. This area lies between CA1 and subiculum (Sub) and particularly lacks consensus on its boundaries; reports have varied on the description of its features and location. In this report, we review, refine, and evaluate four cytoarchitectural features that differentiate ProS from its neighboring subfields: (1) small neurons, (2) lightly stained neurons, (3) superficial clustered neurons, and (4) a cell sparse zone. ProS was delineated in all cases (n = 10). ProS was examined for its cytoarchitectonic features and location rostrocaudally, from the anterior head through the body in the hippocampus. The most common feature was small pyramidal neurons, which were intermingled with larger pyramidal neurons in ProS. We quantitatively measured ProS pyramidal neurons, which showed (average, width at pyramidal base = 14.31 µm, n = 400 per subfield). CA1 neurons averaged 15.57 µm and Sub neurons averaged 15.63 µm, both were significantly different than ProS (Kruskal-Wallis test, p < .0001). The other three features observed were lightly stained neurons, clustered neurons, and a cell sparse zone. Taken together, these findings suggest that ProS is an independent subfield, likely with distinct functional contributions to the broader interconnected hippocampal network. Our results suggest that ProS is a cytoarchitecturally varied subfield, both for features and among individuals. This diverse architecture in features and individuals for ProS could explain the long-standing complexity regarding the identification of this subfield.