1. INTRODUCTION

The hippocampal formation (HC) of mam-mals is a component of the limbic system of thebrain hidden deep within the cerebral hemi-spheres in close association with the medialtemporal lobe. The HC is believed to play animportant role in learning and memory andmay as well, through its limbic connections,play a role in the control of emotional behav-iors and neuroendocrine functions. In highermammals manifesting complex behaviors, suchas cetaceans, proboscideans, and primates, theHC is small relative to the large size of thecerebrum. Although the HC has been well stud-ied in primates, relatively little detailedanatomic information is available concerningthe anatomy of the HC in the elephant (Dexler1907; Haug 1970; Janssen & Stephan 1956;Koikegami et al. 1941). Our objectives havebeen to study the anatomical homologiesbetween the HC of the elephant, a large mam-mal proverbial for its powers of memory, and of

the human and to infer possible functions basedon knowledge from the human HC. The patho-logic involvement of the human HC in neu-rodegenerative diseases associated with old agesuch as Alzheimer’s disease raises the questionof the occurrence of similar changes in elderlyelephants.

2. MATERIALS AND METHODS

We present an anatomic analysis of the HC informaldehyde-fixed brain specimens obtainedfrom an Asian elephant Elephas maximus(female, age 34 years) and an African elephantLoxodonta africana (female, age 46 years).

Our investigations include macroscopicdescriptions of the HC and microscopic analy-sis of histologic preparations using paraffin-embedded material sectioned at 10u andstained with Luxol fast blue/cresyl violet,hematoxylin and eosin, and Bielschowskymethods and 30u sections stained with cresylviolet alone.

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Morphologic analysis of the hippocampal formation in Elephas maximus and Loxodonta africanawith comparison to that of human

W.J. Kupsky1, G.H. Marchant2, K. Cook2, J. Shoshani3

1Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan,USA - wkupsky@dmc.org2Elephant Research Foundation, Michigan, USA - jshosh@sun.science.wayne.edu3Department of Biology, University of Asmara, Asmara, Eritrea (Horn of Africa);hezy@bio.uoa.edu.er, jshosh@sun.science.wayne.edu

SUMMARY: The hippocampal formation (HC) of mammals is a component of the limbic system of the brainhidden deep within the cerebral hemispheres in close association with the medial temporal lobe. Althoughthe HC has been well studied in primates, little anatomic information is available concerning the detailedanatomy of the HC in the elephant, a large mammal proverbial for its powers of memory. We present ananatomic analysis of the HC in an Asian elephant Elephas maximus (female, age 34 years) and in an Africanelephant Loxodonta africana (female, age 46 years). Our investigations include macroscopic descriptions ofthe HC and microscopic analysis of histologic preparations.

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Fig.1 - Location and orientation of the hippocampus in the medial temporal lobe (Elephas maximus).

Fig.2 - Location and orientation of HC (Loxodonta africana). Note relationship of HC to medial wall of lateral ventricle.

3. RESULTS

In both elephant specimens, the HC wasidentified in the medial temporal lobe orientedparallel to the long axis of the lobe (Fig. 1) andforming part of the medial wall of the inferiorhorn of the lateral ventricle (Fig. 2). The HCwas approximately the same size as the humanHC but small relative to the overall size of theelephant cerebrum. The shape was similar tothe human HC but the digitationes hippocampiwere indistinct.

The gyrus dentatus was relatively broad andflat and the fimbria was also relatively broader

and thinner than the human fimbria. The whitematter of the parahippocampal gyrus formed aprominent bulge on the medial floor of the tem-poral horn (Fig. 3). The elephant HC showed asimilar pattern of folding to the human HC, butthe folding was less compact in the end folium.The three-layered archicortical pattern was eas-ily observed (Fig. 4), but the neuronal packingdensity appeared generally less than in thehuman HC and there was a clear distinctionbetween the three-layered pyramidal area CA3along the lateral border of the fascia dentata(FD) and a layer of loosely arranged pyramidalneurons (CA4) within the end folium running

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Morphologic analysis of the hippocampal formation in Elephas maximus and Loxodonta africana...

Fig.3 - Detailed photograph of HC (Elephas maximus). The anterior portion of the pes hippocampi has beendamaged. The fascia dentata is broad and flat. (Photographer: Mr. Benjamin True, Medical Photography).

parallel to the FD. The FD consisted of a broadlamina moleculare, a compact lamina granulareof small bipolar neurons, and a narrow laminaplexiforme containing small cells. In the endfolium, the distinct CA4 layer surrounded acentral hilum of myelinated fibers devoid ofneurons.

There was a distinct transition to pyramidallayer CA3. Ectopic pyramidal neurons in vari-ous orientations were prominent in both thelamina moleculare and lamina plexiforme.Pyramidal layers CA1 and the subiculum weredistinguished by the presence of discrete sub-laminae, with a compactly arranged layer ofpyramidal cells forming the top of layer 2.Scattered large pyramidal neurons were rela-tively abundant in layer 1. Layer 3 includedmore abundant pyramidal neurons intermixedwith small horizontally oriented neurons, mostprominent in the subiculum.

No evidence of Alzheimer-type changes(senile plaques, neurofibrillary tangles-NFT,Hirano bodies, or granulovacuolar degeneration)or other aging changes such as prominent accu-mulation of lipofuscin, mineralization of the HCmicrovasculature, or vascular sclerotic changewas noted in either hippocampal specimen.

4. CONCLUSIONS

HC structures in the elephant appear grosslyand histologically to have the same basic struc-tural components and anatomic disposition asin the human HC. The elephant HC, however, isabout the same size as the human HC and istherefore smaller in proportion to the overallbrain size (Fig. 5). The homologies have possi-ble implications for similar functions (learning,memory, control of behavior). The absence ofHC degenerative changes of the Alzheimer type(senile plaques, NFT, Hirano bodies, granulo-vacuolar degeneration.), which occur in the HCof many elderly humans as well as in humanswith Alzheimer's disease is of uncertain signif-icance.

Degenerative changes were not noted inthree older elephant brains examined by Cole& Neal (1990). Although the ages of the ele-phants we examined (34 and 46 years) mayonly represent somewhat more than half oftheir maximal life span potential, the Africanelephant did show rare NFT in the substan-tia nigra, a non-limbic brainstem structureinvolved with NFT in other forms of humanneurodegenerative disease. This basic researchis part of a long-term systematic study of ele-

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Fig.4 - Low-magnification photomicrograph of mid-portion of HC sectioned perpendicular to the long axis ofthe HC. The fascia dentata and zones of the cornu ammonis (CA) are marked. (Luxol fast blue/cresyl violet,1x original magnification).

phant brain anatomy from both a macroscopicand microscopic perspective whose goal is tofill in missing or misunderstood informationusing a holistic approach to gain knowledge onthe largest living land mammal.

5. REFERENCES

Cole, G. & Neal, J.W. 1990. The brain in agedelephants. Journal of Neuropathology andExperimental Neurology 49: 190-192.

Dexler, H. 1907. Zur Anatomie des Zentralner-vensystems von Elephas indicus. Arb. neur.Inst. Wein 15:137-281.

Haug, H. 1970. Der makroskopische Aufbaudes Grosshirns; Qualitative und quantitativeUntersuchungen an den Gehirnen des Men-schen, der Delphinoideae und des Elefan-ten. Ergebnisse der Anatomie und Entwick-lungsgeschichte 43(4): 3-70.

Janssen, P. & Stephan, H. 1956. Recherches surle cerveau de l’elephant d’Afrique (Lox-odonta africana Blum.). I. Introductions etconsiderations macroscopiques. Acta neuro-logica belgica 56: 731-757.

Koikegami, H., Kido, S. & Mayeda, Y. 1941.Zum Riechhirn des indischen Elephanten.Gegenbaurs morphologisches Jahrbuch 85:512-524.

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Morphologic analysis of the hippocampal formation in Elephas maximus and Loxodonta africana...

Fig.5 - Comparison of elephant and human hippocampus drawn to same scale.