Are the dorsal and ventral hippocampus functionally distinct structures?

Abstract

One literature treats the hippocampus as a purely cognitive structure involved in memory; another treats it as a regulator of emotion whose dysfunction leads to psychopathology. We review behavioral, anatomical, and gene expression studies that together support a functional segmentation into three hippocampal compartments: dorsal, intermediate, and ventral. The dorsal hippocampus, which corresponds to the posterior hippocampus in primates, performs primarily cognitive functions. The ventral (anterior in primates) relates to stress, emotion, and affect. Strikingly, gene expression in the dorsal hippocampus correlates with cortical regions involved in information processing, while genes expressed in the ventral hippocampus correlate with regions involved in emotion and stress (amygdala and hypothalamus).

Fig. 1

Molecular domains of the hippocampal CA1 and CA3. A shows a three dimensional (3D) model of Ammon's horn, which appears as a “C” shaped cylinder with its dorsal and ventral ends towards rostral and medial directions of brain. CA1 occupies the area dorsal, lateral, and caudal to the CA3. B (lateral view) and C (medial view) display heterogenic spatial distribution patterns of several representative marker genes expressed specifically in CA1 (Wfs1, Dcn, Grp, and Htr2c), CA2 (Amigo), or CA3 (Map4k3, Iyd, Itga7, Plagl1, and Coch). Expression of these genes in the Ammon’s horn reveals clear segregation between the dorsal (including CA1d, CA2, CA3d), intermediate (CA1i and CA3i), and ventral (CA1v and CA3v) areas. Expression of these genes were plotted onto representative coronal planes of the Allen Reference Atlas (Dong, 2007) as shown in D, which reveals clear boundaries between these molecular domains in CA1 and CA3. The 3D model and gene expression in Ammon’s horn were generated in BrainExplore (Lau et al, 2008), a 3D application of the Allen Reference Atlas (www.brain-map.org). E illustrates the spatial definition of the CA3i, which appears as an “X”-shaped pyramidal neuronal pool on one particular “re-sliced” sagittal plane of the Allen Reference Atlas (in the middle panel, ~2.494 mm from the middle line). The detailed Nissl-stained cytoarchitecture of the hippocampus is shown side by side. Numbers 1–4 indicate four corners of the “X” shaped pyramidal pool in domain CA3i at this sagittal plane and their corresponding spatial positions on the coronal planes (shown in the dorsal and ventral panels), which indicate the boundaries between the CA3d and CA3i (number 1; number 2 represents the dorsal end of the CA3 at the most caudal level) and between CA3i and CA3v (number 3 at more rostral and 4 more caudal). These images were generated with the AGEA application of the ABA. F shows four representative genes that are expressed preferentially in both domain CA3d and CA3i (Rph3a), CA3i (Loxl1), and CA3v (Plagl1 and Coch). Numbers 1–4 indicate corresponding anatomic locations in E. These gene expression digital images were downloaded from the ABA

Fig. 2

Three dimensional model of the dentate gyrus in the context of the whole mouse brain (A, lateral view) and its spatial relationship with Ammon’s horn (dark green in B, medial view). Two genes, Lct (blue) and Trhr (red), are expressed preferentially in the dorsal/septal one third or ventral/temporal one third of the dentate gyrus respectively. These images were generated in BrainExplorer, one three dimensional version of the ABA (Dong, 2007). Abbreviations: AH, Ammon’s horn; CTX, cerebral cortex; DG, dentate gyrus; HPF, hippocampal formation; OB, olfactory bulb.

Fig. 3

Schematic overview showing the organization of the dorsal hippocampal network Abbreviations: ACA, anterior cingulated area; ACB, nucleus accumbens; ATN, anterior thalamic complex; CP, caudoputamen; DGd, dorsal domain of the dentate gyrus; ENTl, the caudolateral band of the entorhinal cortex; GP, globus pallidus; LM, lateral mammilary nucleus; LSc, the caudal part of the lateral septal nucleus; MM, medial mammilary nucleus; MSC, medial septal complex; PRE, presubiculum; POST, postsubiculum; RSP, retrosplenial cortex; SNr, reticular part of the substantial nigra; SUBd, dorsal subiculum; SUM, supramammillary nucleus; VTA, ventral tegmental area.

Fig. 4

Schematic diagram to illustrate the major neuronal connectivity of the ventral hippocampus. Abbreviations: ACB, nucleus accumbens; AMY, cortical-like amygdalar areas (nuclei); BST, bed nuclei of the stria terminalis; CEA, central amygdalar nucleus; LSr, v, the rostral and ventral parts of the lateral septal nucleus; MEA, medial amygdalar nucleus; MPF, medial prefrontal cortex; SUBv, the ventral subiculum.