Download Cortical inputs to the CA1 field of the monkey hippocampus originate

Neuroscience Letters, 115 (1990) 43-48
Elsevier Scientific Publishers Ireland Ltd.
43
NSL 06983
Cortical inputs to the CA1 field of the monkey
hippocampus originate from the perirhinal and
parahippocampal cortex but not from area TE
W e n d y A. Suzuki 2 and David G. Amaral 1
1The Sail( Institute for Biological Studies and 2The Group in Neurosciences, University of California
at San Diego, San Diego, CA (U.S.A.)
(Received 6 February 1990; Accepted 5 March 1990)
Key words." Hippocampal formation; CAI, Connections; Primate; Area TE; Perirhinal cortex; Parahippocampal cortex
We determined the cortical regions that project directly to the CAI field of the monkey hippocampus
by injecting the retrograde tracers Fast blue, Diamidino yellow or WGA-HRP into CAI and examining
the distribution of labeled cells. In the temporal lobe, large numbers of retrogradely labeled cells were
observed in the perirhinal and parahippocampal cortices. Only an occasional labeled cell, however, was
observed in the unimodal visual area TE. Additional projections to CA1 arose in the dorsal bank of the
superior temporal sulcus, in the rostral and retrosplenial portions of the cingulate cortex, in the agranular
insular cortex, and in the caudal orbitofrontal cortex.
In recent years, a number of reports have emphasized that the primate hippocampal formation* receives direct inputs from several neocortical regions. Van Hoesen
and colleagues [6-8] used anterograde tracing techniques to demonstrate direct projections to the entorhinal cortex and subiculum from the medial temporal lobe and
frontal cortex. Insausti et al. [3] used retrograde tracing techniques to demonstrate
that the strongest cortical projections to the monkey entorhinal cortex originate in
a band of cortex that lies laterally adjacent to the hippocampal formation and comprises the perirhinal cortex (areas 35 and 36) and the parahippocampal cortex (areas
TF and TH). Other projections originated from the dorsal bank of the superior temporal sulcus, the insular cortex, the orbitofrontal cortex and the cingulate cortex,
especially the retrosplenial region. The major unifying characteristic of the cortical
areas that project to the entorhinal and subicular cortices is that, on anatomical
grounds, they are regions of polymodal sensory convergence [5].
"In the term hippocampal formation we include the dentate gyrus, the hippocampus proper, the subicular
complex and the entorhinal cortex.
Correspondence: D.G. Amaral, The Salk Institute, P.O. Box 85800, San Diego, CA 92138, U.S.A.
0304-3940/90/$ 03.50 © 1990 Elsevier Scientific Publishers Ireland Ltd.
44
More recently, Yukie and Iwai [9,4] reported that the unimodal visual area TE is
also directly interconnected with CAI of the monkey hippocampus. They placed
injections of W G A - H R P into a ventromedial portion of the medial temporal lobe,
referred to as the ventral portion of area TE (TEv), and observed retrogradely labeled cells in the CAI field. Fine granular particulate staining in the stratum lacunosum-moleculare of CA I was interpreted as anterogradely transported label. Since
area TE is considered to be a unimodal visual associational area [2,5] that does not
project to the entorhinal cortex [3], a projection from TE to CA I would indicate that
the hippocampus receives a different type of sensory innervation than the entorhinal
cortex. The most direct way of evaluating the origin of temporal lobe projections to
CA I is by placing a retrograde tracer into CA I and determining the distribution of
retrogradely labeled cells. We report the results of experiments of this type in this
paper.
A library of 5 experiments with injections of the retrograde tracers Fast blue (FB)
or Diamidino yellow (DY) into various fields of the hippocampal formation were
available from a previous study [10]. The two tracers were injected on both sides of
the brain at different rostrocaudal levels of the hippocampal formation and thus 20
injections were available for analysis. In three additional experiments, discrete injections of the retrograde tracers FB, DY or W G A - H R P were placed into different rostrocaudal levels of the medial portion of the CAi field of the hippocampus. After
a survival period of two weeks (or 2 days in the case of W G A - H R P injections), the
animals were sacrificed and the brains processed for histological examination.
In experiments M-2-87 and M-7-89, at least one of the injections exclusively
involved the CAI field. The FB injection in M-7-89 consisted of 800 nl of a 3% FB
solution. A l-in-8 series of 30/tm sections through the entire brain was analyzed and
the cells located in every other of these sections was plotted and counted using a computer-aided digitizing system. The DY injection on the left side of M-2-87 consisted
of 200 nl of 2% DY solution and the sections were analyzed as described above. In
our library of cortical [3H]amino acid injections, one experiment (M-4-88) consisted
of a 50 nl injection of a 100/~Ci//tl solution of [3H]leucine and [3H]proline into area
TF of the parahippocampal cortex. This brain was prepared autoradiographically for
the demonstration of anterogradely transported label and will be used to illustrate
the terminal field of CA 1 cortical afferents. The cytoarchitectonic organization of the
perirhinal and parahippocampal cortices has been described previously [I, 3]. The
border between areas 36 or TF and the laterally adjacent area TE is not sharp. The
transition between areas 36 or TF and area TE appears to have characteristics intermediate between them and we have labeled this area (36 or TF)/TE in Figs. 1 and 2.
The injection in experiment M-7-89 was confined to CA 1 of the caudal hippocampus and was focused in stratum lacunosum-moleculare (Fig. 1). This injection was
located at approximately the location that Yukie and Iwai [9] observed the strongest
projection from their injections. Thus, based on their report, one might expect to observe large numbers of labeled cells in area TE. However, in the analyzed sections,
only 4 retrogradely labeled cells from a total of 4095 cells plotted in the inferior temporal lobe were observed in area TE. Moreover, only an additional 84 cells were
45
M7"89/
CELLS
CELL
2 CELLS
TE:lC
T E : I CELL
0 CELLSIII;I~I!I:
INJECTION SITE
Fig. 1. Line drawings of representative coronal section through the temporal lobe in experiment M-7-89
showing the distribution and number of retrogradely labeled cells in the inferior temporal lobe. The boundaries of areas 35, 36, TH, TF, and the (36 or TF)/TE transition region are indicated in each section by
different shades of gray (see legend at top right). Indicated above each section is the number of retrogradely labeled cells observed in each of the outlined areas.
46
iiiii0
1
0
CELLS
100 CELLS
INJECTION SITE
Fig. 2. Line drawings of representative coronal sections through the temporal lobe in experiment M-2-87
indicating the distribution and number of retrogradely labeled cells in the inferior temporal lobe. Definitions of areas are the same as in Fig. 1. Indicated above each section is the number of retrogradely labeled
cells observed in each of the outlined areas.
47
found in the transitional region between areas 36 or T F and TE. Taken together these
cells account for only 2.1% of the retrogradely labeled cells in the inferior temporal
cortex. The greatest number of labeled cells was observed in the perirhinal and parahippocampal cortices. There were 2914 labeled cells (or 72%) observed in area 36 and
615 labeled cells (or 12%) in area 35. Approximately 12% of the cells were observed
in areas TF and TH. Labeled cells were also observed in the cingulate cortex (205
cells), the dorsal bank of the rostral superior temporal sulcus (122 cells), the agranular insular cortex (26 cells) and caudal area 13a of the orbitofrontal cortex (24 cells).
In M-2-87, (Fig. 2) the injection was somewhat smaller than in M-7-89 and was
located rostrally in CA 1. There were no labeled cells in area TE and only a few cells
found in the transition region. As in M-7-89, the largest number of retrogradely labeled cells was observed in area 36. We did not observe any larger number of labeled
cells in area TE in any of the other retrograde cases available for analysis.
In all cases in which [3H]amino acid injections involved areas 36 or TF, anterogradely labeled fibers and terminals were observed in the deep portion of the stratum
lacunosum-moleculare of C A l . In experiment M-4-88, the injection was confined to
area TF and the anterogradely transported label was distributed mainly to the medial
portion of CA1 (Fig. 3) and also extended into the transition region between CAI
Eq
TH
INJECTION
SITE
TF
Fig. 3. Line drawings of representative coronal sections through the hippocampal formation arranged
from rostral (A) to candal (C), in experiment M-4-88 indicating the distribution of anterograde labeling
resulting from an injection of [3H]amino acids into area TF of the parabippocampal cortex. The levels
of shading directly correspond to the observed density of autoradiographic grains. Abbreviations: CAI,
CA3, fields of the hippocampus; DG, dentate gyrus; EC, entorhinal cortex; PaS, parasubiculum; PrS, presubiculum; S, subiculum; TF, TH, fields of the parahippocampal gyrus.
48
and the subiculum. The density of labeling in CAI appeared to be relatively light
in comparison to the heavy innervation of the entorhinal cortex (Fig. 3).
We conclude from these studies that the same regions of the ventral temporal lobe
that project to the entorhinal cortex also project to CA1. These projections originate
mainly from areas 35 and 36 of the perirhinal cortex, and areas TF and TH of the
parahippocampal cortex. We observed a sharp drop in the number of labeled cells
in the transitional region between these areas and area TE and there was only an
occasional retrogradely labeled cell in cortex that clearly met the cytoarchitectonic
definition of area TE. It would appear, therefore, that the CA 1 field of the hippocampus does not receive a strong unimodal visual input via area TE but, like the entorhinal cortex, receives multimodal sensory information from the perirhinal and parahippocampal cortices. Based on our interpretation of the illustrations in Yukie and lwai
[9] it appears that the injections yielding anterograde transport to the CA I field partially involved the lateral aspects of areas 36 or TF according to our delimitation of
these fields. We would suggest, therefore, that the CA 1 projections that they demonstrated arise primarily from the perirhinal and parahippocampal cortices rather than
from area TE.
We would like to thank Dr. Ricardo Insausti for help with some of the preparations used in this study and to Ms. Janet Weber and Ms. Mary Ann Lawrence for
histological assistance. This work was supported by NIH Grant NS 16980.
I Amaral, D.G, Insausti, R. and Cowan, W.M., The entorhinal cortex of the monkey: 1. Cytoarchitectonic organization, J. Comp. Neurol., 264 (1987) 32(y 355.
2 Desimone, R. and Gross, C.G., Visual areas in the temporal cortex of the macaque, Brain Res., 178
(1979) 363 -380.
3 Insausti, R., Amaral, D.G. and Cowan, W.M., The entorhinal cortex of the monkey: II. Cortical afterents, J. Comp. Neurol., 264 (1987) 356- 395.
4 Iwai, E. and Yukie, M., A direct projection from hippocampal field CAI to ventral area TE ofinferotemporal cortex in the monkey, Brain Res., 444 (1988) 397401.
5 Pandya, D. N. and Yeterian, E. H., Architecture and connections of cortical association areas. In A.
Peters and E.G. Jones (Eds.), Cerebral Cortex, Association and Auditory Cortices, Vol. 4, Plenum
Press, New York, 1984, pp. 3-61.
6 Van Hoesen, G.W. and Pandya, D.N., Some connections of the entorhinal (area 28) and perirhinal
(area 35) cortices of the rhesus monkey. I. Temporal lobe afferents, Brain Res., 95 (1975) I 24.
7 Van Hoesen, G.W., Pandya, D.N. and Butters, N., Some connections of the entorhinal (area 28) and
perirhinal (area 35) cortices of the rhesus monkey. II. Frontal lobe afferents, Brain Res., 95 (1975)
25 38.
8 Van Hoesen, G.W., Rosene, D.L. and Mesulam, M.M., Subicular input from temporal cortex in the
rhesus monkey, Science, 205 (1979) 608~610.
9 Yukie, M. and Iwai, E., Direct projections from ventral TE area of the inferotemporal cortex to hippocampal field CAI in the monkey, Neurosci. Lett., 88 (1988) 6- 10.
10 Witter, M.P., Van Hoesen, G. W. and Amaral, D. G., Topographical organization of the entorhinal
projection to the dentate gyrus of the monkey, J. Neurosci., 9 (1989) 216-228.