Medial temporal lobe projections to the retrosplenial cortex of the macaque monkey

Abstract

The projections to the retrosplenial cortex (areas 29 and 30) from the hippocampal formation, the entorhinal cortex, perirhinal cortex, and amygdala were examined in two species of macaque monkey by tracking the anterograde transport of amino acids. Hippocampal projections arose from the subiculum and presubiculum to terminate principally in area 29. Label was found in layer I and layer III(IV), the former seemingly reflecting both fibers of passage and termination. While the rostral subiculum mainly projects to the ventral retrosplenial cortex, mid and caudal levels of the subiculum have denser projections to both the caudal and dorsal retrosplenial cortex. Appreciable projections to dorsal area 30 [layer III(IV)] were only seen following an extensive injection involving both the caudal subiculum and presubiculum. This same case provided the only example of a light projection from the hippocampal formation to posterior cingulate area 23 (layer III). Anterograde label from the entorhinal cortex injections was typically concentrated in layer I of 29a-c, though the very caudal entorhinal cortex appeared to provide more widespread retrosplenial projections. In this study, neither the amygdala nor the perirhinal cortex were found to have appreciable projections to the retrosplenial cortex, although injections in either medial temporal region revealed efferent fibers that pass very close or even within this cortical area. Finally, light projections to area 30V, which is adjacent to the calcarine sulcus, were seen in those cases with rostral subiculum and entorhinal injections. The results reveal a particular affinity between the hippocampal formation and the retrosplenial cortex, and so distinguish areas 29 and 30 from area 23 within the posterior cingulate region. The findings also suggest further functional differences within retrosplenial subregions as area 29 received the large majority of efferents from the subiculum.

FIGURE 1

Photomicrographs (A–D) of Nissl stained coronal sections from a cynomolgus macaque (Macaca fascicularis) showing the location and arrangement of the retrosplenial cortex (areas 29 and 30). Photomicrographs 1A and 1B, which are the most rostral, show the dorsal retrosplenial cortex, i.e., above the corpus callosum. The numbers indicate the rostro-caudal location of the sections relative to the interaural line (mm) according to the atlas of Paxinos et al. (2009). The outline figure (E), which shows the major features of the medial surface of the macaque brain, has four vertical lines (A–D) that correspond to the positions of the coronal sections in Figures 1A–D. The scale bars on Figures 1A and 1B represent 0.5 mm, the scale bars on Figures 1C and 1D represent 1.0 mm. CC, corpus callosum; CF, callosal fissure; CG, cingulum; DG, dentate gyrus; HF, hippocampal fissure; IG, indusium griseum; LV, lateral ventricle; PS, presubiculum, S, subiculum; TC, tail of caudate. The roman numerals refer to the lamina within the retrosplenial cortex. The arrow on Figure 1D points to the caudal junction of the hippocampal and callosal fissures.

FIGURE 2

Location and extent of the amino acid injections into the amygdala. The injection sites are depicted on standard coronal sections at the level of the middle and caudal third of the amygdala. ACB, accessory basal nucleus; AHA, amygdalo-hippocampal area; Bi, basal nucleus, intermediate division; Bmc, basal nucleus, magnocellular division; Bpc, basal nucleus, parvocellular division; Ce, central nucleus; Co, cortical nucleus; HPC, hippocampus; LAT, lateral nucleus; Me, medial nucleus.

FIGURE 3

Drawings of two coronal sections showing the path of autoradiographic label in the posterior cingulate region in the case with the largest amygdala injection (ACy6). (Fig. 3A is the more rostral.) While labeled fibers were present in the posterior cingulate region, no termination could be seen. CC, corpus callosum; CG, parahippocampal cingulum; CS, calcarine sulcus; IG, indusium griseum; LV, lateral ventricle; PS, presubiculum; S, supracallosal subiculum; TC, tail of caudate. The scale bar on the photomicrograph represents 2.0 mm, whereas that on the drawing represents 500 μm.

FIGURE 4

Location and extent of the amino acid injection placements in the hippocampal formation drawn onto standard coronal sections. The injection sites in the normal animals are depicted in the upper box, those in cases where the fornix had been transected before injection are shown in the lower box. Amy, amygdala; DG, dentate gyrus; Hpc, hippocampus; PaS, parasubiculum; PrS, presubiculum; S, subiculum.

FIGURE 5

Case ACy14—rostral subiculum injection. Dark-field photomicrographs and line drawings of coronal sections through the posterior cingulate region showing the distribution of anterograde label, including fibers, after an amino acid injection centered in the rostral subiculum. Sections A–D go from rostral to caudal. The locations of the dark-field photomicrographs are indicated by arrows. CC, corpus callosum; CG, parahippocampal cingulum; DG, dentate gyrus; FF, fimbria fornix; IG, indusium griseum; LV, lateral ventricle; P, pulvinar; PS, presubiculum; S, subiculum; TC, tail of caudate. The scale bar on the bright-field photomicrograph represents 2.0 mm, whereas that on the dark-fields represents 500 μm.

FIGURE 6

Case ACyF15—mid subiculum injection. Dark-field photomicrographs and line drawings of coronal sections through the posterior cingulate region showing the distribution of anterograde label, including fibers, after an amino acid injection centered in the mid subiculum. Sections A–E go from rostral to caudal. The locations of the dark-field photomicrographs are indicated by arrows. CC, corpus callosum; DG, dentate gyrus; IG, indusium griseum; LV, lateral ventricle; P, pulvinar; PS, presubiculum; S, subiculum. The scale bar by the bright-field photomicrograph represents 2.0 mm, whereas that on the dark-fields represents 500 μm.

FIGURE 7

Case ACy28—caudal hippocampus injection (see also Fig. 8). Dark-field photomicrographs and line drawings of coronal sections through the posterior cingulate region that show the distribution of anterograde label, including fibers, after an amino acid injection centered in the caudal hippocampus, including the subiculum. Sections A–G go from rostral to caudal. The locations of the dark-field photomicrographs are indicated by arrows. CC, corpus callosum; FF, fimbria fornix; IG, indusium griseum; LV, lateral ventricle; P, pulvinar; PS, presubiculum; S, subiculum. The scale bar on the bright-field photomicrograph represents 2.0 mm, whereas that on the dark-fields represents 500 μm.

FIGURE 8

Case ACy28 (continued from Fig. 7)—caudal hippocampus injection. Figures 8A and 8B depicts two sections just caudal to those in Figure 7E. The coronal section in the dark-field photomicrograph (8A) is just anterior to line drawing of a coronal section at the posterior limit of the retrosplenial cortex (8B). Both sections 8A and 8B show the distribution of anterograde label, including fibers, after an amino acid injection centered in the caudal hippocampus, including the subiculum. CG, parahippocampal cingulum; IG, indusium griseum; S, subiculum. The scale bar represents 500 μm.

FIGURE 9

Case ERh3—entorhinal cortex injection. Dark-field photomicrographs and line drawings of a coronal section at the caudal limit of the retrosplenial cortex, showing the distribution of anterograde label, including fibers. The locations of the dark-field photomicrographs are indicated by arrows. CS, calcarine sulcus; IG, indusium griseum; LV, lateral ventricle; S, subiculum. The scale bar by the bright-field photomicrograph represents 2.0 mm, whereas that on the dark-field photomicrographs represents 500 μm.

FIGURE 10

Case AF27R—rostral subiculum, presubiculum, and caudal rhinal cortex injection. Dark-field photomicrographs and line drawings of coronal sections through the posterior cingulate region showing the distribution of anterograde label, including fibers, in Case AF27R which received two injections in the rostral hippocampal formation; (1) in presubiculum and adjacent subiculum, (2) in very caudal perirhinal cortex and deep layers of adjacent entorhinal cortex. Sections A–C go from rostral to caudal. The locations of the dark-field photomicrographs are indicated by arrows. The bright field photomicrograph of Section C shows how the terminal label was concentrated in the granule cells [layer III(IV)] of area 29a–c. CG, parahippocampal cingulum; IG, indusium griseum; LV, lateral ventricle; PS, presubiculum; S, subiculum. The scale bar on the bright-field photomicrograph represents 2.0 mm, whereas that on the dark-fields represents 500 μm.

FIGURE 11

Schematic drawings illustrating the routes of the various projections from the hippocampus (subiculum) and entorhinal cortex to the retrosplenial region. A (left) depicts the coronal plane (midline to the right). The arrows show both the routes of fibers and potential sites of termination, whereas the thickness of the lines reflects the density of label. The large majority of projections from the hippocampus pass immediately medial to the merging of the hippocampal and callosal fissures. In contrast, the principal fiber route from the rhinal cortices is in the indusium griseum and, hence, is lateral to the junction of the hippocampal and callosal fissures. B (right) depicts the parasagittal plane. The stronger affinity of the hippocampal formation with area 29 than area 30 is depicted, along with the scarcity of projections to area 23. CC, corpus callosum; cg, cingulum; HPC, hippocampus; IG, indusium griseum; S, subiculum; SS, supracallosal subiculum. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]