Divergent projections from the anterior inferotemporal area TE to the perirhinal and entorhinal cortices in the macaque monkey

Abstract

Area TE is located at the latter part of the ventral visual cortical pathway, which is essential for visual recognition of objects. TE projects heavily to the perirhinal region, which is important for visual recognition memory of objects. To study the organization of projections from TE to the perirhinal (areas 35 and 36) and entorhinal (area 28) cortices, we made focal injections of Phaseolus vulgaris leucoagglutinin (PHA-L) and large injections of biocytin or wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into anterior levels of TE in macaque monkeys. Injections of PHA-L into the ventral part of anterior TE (TEav) resulted in labeling of terminals distributed widely in area 36 (approximately one-half of its total extent), although the injection sites were limited to 0.7 mm in width. The labeled terminals tended to be denser in the medial part of area 36. There was less dense but definite labeling in area 35 and the lateral part of area 28. After a single injection of PHA-L or WGA-HRP into the dorsal part of anterior TE (TEad), labeled terminals were confined to a small region at the lateral part of area 36 (less than one-tenth of its total extent). The projections to areas 35 and 28 from TEad were much sparser than those from TEav. The different patterns of projections to the perirhinal and entorhinal cortices, together with previously reported differences in their afferent and other efferent connections, suggest the functional differentiation between TEav and TEad. The divergent projection from TEav to the perirhinal cortex may facilitate the association of different visual features in the perirhinal cortex.

Fig. 7.

Distribution of anterogradely labeled terminals after PHA-L, biocytin, and WGA-HRP injections into TEav. Thefilled region indicates the extent of the injection site, and the small dots at different densities represent the terminal labeling. All other conventions are as in Figure 1.

Fig. 8.

Distribution of anterogradely labeled terminals after PHA-L and WGA-HRP injections into TEad. The flattened map in one case (F), in which the injection was made in the left side, was reversed for convenience of comparison. All conventions are as in Figure 1.

Fig. 1.

Location of the subdivisions of area TE, perirhinal cortex (areas 35 and 36), and the entorhinal cortex (area 28). A ventral view of the brain is shown at the top left. The portion of the brain circumscribed by the broken linewas unfolded to produce the two-dimensional map shown at the top right. The solid lines indicate the lips of the sulci, and the dotted lines show the borders between cortical areas and their subdivisions. In contrast to the conventional unfolding, the coronal sections are represented by vertical straight linesin the map in this study. Camera lucida drawings of three representative coronal sections are shown at the bottom.Shaded areas in the coronal sections indicate the areas included in the two-dimensional map. sts, Superior temporal sulcus; amts, anterior middle temporal suclus;rs, rhinal sulcus; ots, occipitotemporal sulcus;HC, hippocampus; Amy, amygdala; C, caudal; R, rostral; M, medial; L, lateral.

Fig. 2.

Cytoarchitectonic subdivision of anterior TE, perirhinal cortex, and the entorhinal cortex. A, Nissl-stained coronal section. The arrowheads indicate the borders between different areas. There is a clear distinction between layers IV, V, and VI in TEad, but it is less prominent inTEav. B, Adjacent section stained immunohistochemically for parvalbumin. There is a clear decrease in the density of immunostaining at the border from TEav to area36. Both neurons and neuropil are more lightly stained in area 36 than in TEav. The parvalbumin staining is even lighter in area 35, but suddenly becomes dense at the border from area 35 to area 28. Scale bars, 2 mm.

Fig. 3.

Cytoarchitecture of TEav, the caudal part of area 36 (36c), area 35, and area 28. A, Nissl-stained section. There is a separation between layers V and VI in TEav but not in 36c. Layer IV is present in area 36 but absent in areas 35 and 28. The presence of intensely stained large neurons in layer II distinguishes area 28 from area 35. B, A part of TEav and36c, between the two parallel lines in A, is shown at higher magnification. Roman numerals indicate the cortical layers. The distinction between IIIA andIIIB is obvious in 36c, but not inTEav. Similarly, densely stained large pyramidal neurons in layer V are more numerous in 36c than inTEav. Scale bars: A, 1 mm; B, 0.5 mm. All other conventions are as in Figure 1.

Fig. 4.

Cytoarchitecture of TEav and the rostral part of area 36 (36r) in a Nissl-stained section. The position of the photomicrograph is indicated by the box in the lower-magnification line drawing of the section on theright. The subdivision of layer III into IIIA andIIIB is clearer in 36r than in 36c (Fig. 3), and layer II is more distinctive with many darkly stained neurons and satellite glial cells in 36r. Such distinction is not clear in TEav. Scale bar, 0.5 mm.

Fig. 5.

Cytoarchitecture of the polar part of area 36 (36p) in a Nissl-stained section. The position of the photomicrograph is indicated by the box in the line drawing of the section at the top. The distinction between IIIA andIIIB, and that between V and VI, is not clear. Also, layer IV is less distinctive than those in 36c and 36r. Scale bar, 0.5 mm.

Fig. 6.

Photomicrographs illustrating the PHA-L injection sites in TEav (A) and TEad (B). Sections were counterstained for Nissl. Injections in both cases involved all of the cortical layers. Scale bars, 1 mm. All conventions are as in Figure1.

Fig. 9.

Caudorostrally elongated core regions and laminar distribution of terminals in area 36 after a PHA-L injection into TEav. A series of coronal sections at regular intervals of 160 μm is shown (A–E). The inset at the top left illustrates the rostrocaudal levels of these sections on the same drawing as shown in Figure 7A.

Fig. 10.

Dark-field photomicrograph of a dense core region in area 36, which is illustrated at the bottom right within the circumscribed area (same as Fig. 9A). The high-magnification photomicrograph of terminals with boutons (bright-field) at the top right is taken from layer III of the photomicrograph shown at the left. Scale bars:left, 0.25 mm; right, 0.1 mm.

Fig. 11.

Caudorostrally elongated core regions and laminar distribution of terminals in area 36 after a PHA-L injection into TEad. A series of coronal sections at regular intervals of 150 μm is shown (A–E). The figure on the leftillustrates the rostrocaudal levels of these sections on the same drawing as shown in Figure 8A.

Fig. 17.

Photomicrograph illustrating the retrogradely labeled neurons and anterogradely labeled terminals in TEav and area 36r, after WGA-HRP injection into TEad. This photomicrograph was taken from the circumscribed area of section 62 illustrated at thetop right. Its caudorostral level is indicated by thethin line in the top middle drawing, which is the same as Figure 8D. The distribution of labeled neurons extended more medially, beyond the medial limit of the distribution of labeled terminals. Scale bar, 0.5 mm.

Fig. 12.

Single axon projecting from TEad to area 36c. It was reconstructed from serial PHA-L-labeled sections of the TEad-injection case shown in Figure 8A. Thenumbers indicate the serial numbers of individual sections (30 μm thickness) counted from caudal to rostral. The global positions of the arbors are shown in low-magnification drawings of two sections on the left. Arrowheads indicate the borders between different areas. The rostrocaudal levels of the two sections are indicated on the flattened map of the brain shown at thetop right. This axon had two main branches, and the overall caudorostral extent of the arbors was 0.87 mm (271–300). The left branch had two arbors (282–289 and 292–300), which were located in the left core region indicated by “A” in the low-magnification drawing of section 297. The terminal arbors were elongated vertically to the cortical layers expanding from layer VI to layer I. The right branch had one arbor (271–276) located in the right core region indicated by “B” in the low-magnification drawing of section276. The terminals were distributed from layer VI to layer III. The main axon trunk ran into the white matter (WM) and approached the injection site. All other conventions are as in Figure1.

Fig. 13.

Single axon projecting from TEad to areas 36r and 35 reconstructed from the case shown in Figure 8A. This axon had three main branches. One branch was subdivided further into two arbors extending from layer V or IV to layer I (A, 432–442;B, 451–458). The position of the arbor marked by “B” is indicated by the arrow in the low-magnification drawing of section 454. It was located at the lip of the rhinal sulcus in area 36r. The second branch had two arbors, one confined to layer III (C, 490–497) and the other extending from layer V to layer II (D, 498–507). Both were confined to area 35 in the fundus of the rhinal sulcus. The location of the arbor marked by “C” is shown by the arrow in the low-magnification drawing of section 494. The third branch, which was not traced further, ran into the white matter toward other structures. The overall span of the arbors was 2.2 mm along the caudorostral axis (432–507).

Fig. 14.

Single axon projecting from TEad to TEav and area 36c reconstructed from the case shown in Figure 8A. In contrast to Figures 12 and 13, the low-magnification drawing of the section at the top left schematically indicates the locations of the arbors, which actually appeared in different sections. This axon had five arbors, and they all extended from layer III to layer I, except one small arbor that was confined to layer III (E). The overall caudorostral extent of the arbors was 2.2 mm (314–388). Three of the arbors were located in TEav (A–C) and the others in the lateral portion of area 36c (D, E). The main axon trunk ran through the upper layers toward the injection site.

Fig. 15.

Distribution of retrogradely labeled neurons after WGA-HRP injection into TEav. Top two rows, A series of coronal sections, at intervals of 2 mm, in which the filledregion indicates the injection site and the dotsrepresent retrogradely labeled neurons. Only labeled neurons medial to the injection site are shown here and in the drawing shown at thebottom left. Bottom left, The global distribution of labeled neurons in the flattened map, in which a single largedot indicates a group of five neurons and smalldots indicate single neurons. The positions of the coronal sections are also indicated. Bottom right, The global distribution of labeled terminals in the same case (the same drawing as Fig. 7C).

Fig. 16.

Distribution of retrogradely labeled neurons after WGA-HRP injection into TEad. A series of coronal sections, at regular intervals of 1 mm, with labeled neurons plotted asdots (top and bottom left rows), and also flattened maps showing the global distribution of labeled neurons (bottom middle) and terminals (bottom right). This is the same case as that shown in Figure 8E. Only labeled neurons medial to the injection site are shown in the coronal sections and in the flattened map.

Fig. 18.

Summary diagram of the projections from TEav (left) and TEad (right) to the perirhinal and entorhinal cortices. Heavy solid lines indicate dense projection, thin solid lines denote moderate projection, andbroken lines indicate weak projection.