The diencephalon of two carnivore species: The feliform banded mongoose and the caniform domestic ferret

This study provides an analysis of the cytoarchitecture, myeloarchitecture, and chemoarchitecture of the diencephalon (dorsal thalamus, ventral thalamus, and epithalamus) of the banded mongoose (Mungos mungo) and domestic ferret (Mustela putorius furo). Using architectural and immunohistochemical stains, we observe that the nuclear organization of the diencephalon is very similar in the two species, and similar to that reported in other carnivores, such as the domestic cat and dog. The same complement of putatively homologous nuclei were identified in both species, with only one variance, that being the presence of the perireticular nucleus in the domestic ferret, that was not observed in the banded mongoose. The chemoarchitecture was also mostly consistent between species, although there were a number of minor variations across a range of nuclei in the density of structures expressing the calcium‐binding proteins parvalbumin, calbindin, and calretinin. Thus, despite almost 53 million years since these two species of carnivores shared a common ancestor, strong phylogenetic constraints appear to limit the potential for adaptive evolutionary plasticity within the carnivore order. Apart from the presence of the perireticular nucleus, the most notable difference between the species studied was the physical inversion of the dorsal lateral geniculate nucleus, as well as the lateral posterior and pulvinar nuclei in the domestic ferret compared to the banded mongoose and other carnivores, although this inversion appears to be a feature of the Mustelidae family. While no functional sequelae are suggested, this inversion is likely to result from the altricial birth of Mustelidae species.     

The amygdaloid body of two carnivore species: The feliform banded mongoose and the caniform domestic ferret

The current study provides an analysis of the cytoarchitecture, myeloarchitecture, and chemoarchitecture of the amygdaloid body of the banded mongoose (Mungos mungo) and domestic ferret (Mustela putorius furo). Using architectural and immunohistochemical stains, we observe that the organization of the nuclear and cortical portions of the amygdaloid complex is very similar in both species. The one major difference is the presence of a cortex‐amygdala transition zone observed in the domestic ferret that is absent in the banded mongoose. In addition, the chemoarchitecture is, for the most part, quite similar in the two species, but several variances, such as differing densities of neurons expressing the calcium‐binding proteins in specific nuclei are noted. Despite this, certain aspects of the chemoarchitecture, such as the cholinergic innervation of the magnocellular division of the basal nuclear cluster and the presence of doublecortin expressing neurons in the shell division of the accessory basal nuclear cluster, appear to be consistent features of the Eutherian mammal amygdala. The domestic ferret presented with an overall lower myelin density throughout the amygdaloid body than the banded mongoose, a feature that may reflect artificial selection in the process of domestication for increased juvenile‐like behavior in the adult domestic ferret, such as a muted fear response. The shared, but temporally distant, ancestry of the banded mongoose and domestic ferret allows us to generate observations relevant to understanding the relative influence that phylogenetic constraints, adaptive evolutionary plasticity, and the domestication process may play in the organization and chemoarchitecture of the amygdaloid body.     

Radioautographic study of the rat brain after injection of [1,2-3H]corticosterone.

Cryostat sections of the central nervous system of adrenalectomized male rats injected with [3H]corticosterone were examined by radioautography. One hour after the injection, radioactivity was found to be selectively concentrated in specific neurons of the septum, the hippocampal complex (precommissural hippocampus, cornu Ammonis, gyrus dentatus, subiculum), the indusium griseum, the amygdala and in certain areas of the cortex. In the hippocampus, the pyramidal neurons in fields CA1 and CA2 of the cornu Ammonis and the granule neurons of the gyrus dentatus contained more radioactivity than did other regions of the brain. Most of the silver grains were localized in the nuclei of labeled cells. The topographic distribution of corticosterone-concentrating neurons shows that the hormonal target sites in the central nervous system are mainly extrahypothalamic.     

Hippocampal neuron number in schizophrenia. A stereological study.

Neuropathologic and neuroradiologic studies have reported hippocampal abnormalities in schizophrenics. We estimated the total number of neurons in the hippocampus of schizophrenics and controls to elucidate the neuronal basis of such changes. Thirteen brains of schizophrenics and 13 control brains closely matched for sex and age were studied. A new stereological method was applied to serial coronal sections through the whole hippocampus. Total hippocampal volume was reduced in the schizophrenic sample, more pronounced on the left side, but mean differences were not significant. The volumes of the pyramidal cell layer in the four subdivisions subiculum and cornu Ammonis sectors CA 1, CA 2/3, and CA 4 were almost identical in both groups. Schizophrenics did not differ from controls with regard to nerve cell density in any of the four subdivisions. The estimates of the total number of neurons in the hippocampal subdivisions were not different between schizophrenics and controls. The data do not support the hypothesis that hippocampal abnormalities are caused by neuronal cell loss. However, they are consistent with the suggestion that white matter changes in the hippocampus may play a role in the pathogenesis of schizophrenia.     

Pattern of neuronal loss in the rat hippocampus following experimental cardiac arrest-induced ischemia.

The pattern of neuronal loss in the rat hippocampus following 10-min-long cardiac arrest-induced global ischemia was analyzed using the unbiased, dissector morphometric technique and hierarchical sampling. On the third day after ischemia, the pyramidal layer of sector CA1 demonstrated significant (27%) neuronal loss (P<0.05). At this time, no neuronal loss was observed in other cornu Ammonis sectors or the granular layer of the dentate gyrus. On the 14th postischemic day, further neuronal loss in the sector CA1 pyramidal layer was noticed. At this time, this sector contained 31% fewer pyramidal neurons than on the third day (P<0.05) and 58% fewer than in the control group (P<0.01). On the 14th day, neuronal loss in other hippocampal subdivisions also was observed. The pyramidal layer of sector CA3 contained 36% fewer neurons than in the control group (P<0.05), whereas the granular layer of the dentate gyrus contained 40% fewer (P<0.05). The total number of pyramidal neurons in sector CA2 remained unchanged. After the 14th day, no significant alterations in the total number of neurons were observed in any subdivision of the hippocampus until the 12th month of observation. Unbiased morphometric analysis emphasizes the exceptional susceptibility of sector CA1 pyramidal neurons to hypoxia/ischemia but also demonstrates significant neuronal loss in sector CA3 and the dentate granular layer, previously considered 'relatively resistant'. The different timing of neuronal dropout in sectors CA1 and CA3 and the dentate gyrus may implicate the existence of region-related properties, which determine earlier or later reactions to ischemia. However, the hippocampus has a unique, unidirectional system of intrinsic connections, whereby the majority of dentate granular neuron projections target the sector CA3 pyramidal neurons, which in turn project mostly to sector CA1. As a result, the early neuronal dropout in sector CA1 may result in retrograde transynaptic degeneration of neurons in other areas. The lack of neuronal loss in sector CA2 can be explained by the resistance of this sector to ischemia/hypoxia and the fact that this sector is not included in the major chain of intrahippocampal connections and hence is not affected by retrograde changes.     

Neurons and extracellular neurofibrillary tangles in the hippocampal subdivisions in early-onset familial Alzheimer's disease: A case study

Abstract  We have investigated morphometrically unaffected neurons, intracellular neurofibrillary tangles (I-NFT) and extracellular neurofibrillary tangles (E-NFT) in eight subdivisions of the hippocampal cortex in two cases of early-onset familial Alzheimer's disease (FAD) and six cases of early-onset sporadic Alzheimer's disease (SAD). The hippocampal subdivisions examined included: CA4, CA3, CA2, CAI, prosubiculum, subiculum and presubiculum (PRE), parasubiculum (PARA) and entorhinal cortex (ENT). CA3, CA2 and CAI in the FAD cases showed more severe neuronal loss and much greater E-NFT formation than in the SAD cases, while ENT in both the FAD cases showed less neuronal loss and less E-NFT formation. These data suggest that the cornu ammonis is affected more severely than the ENT in the FAD cases. These observations indicate that hippocampal pathology in the FAD cases is qualitatively as well as quantitatively different from that in sporadic cases. These results provide further evidence for pathological heterogeneity in AD, although the number of FAD cases examined is very small.     

Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy

The aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonace (MR)-based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty-three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR-based HCV measurement and HCT2 mapping, therfore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.     

Automated measurement of hippocampal subfields in PTSD: Evidence for smaller dentate gyrus volume

Smaller hippocampal volume has been consistently observed as a biomarker of posttraumatic stress disorder (PTSD). However, less is known about individual volumes of the subfields composing the hippocampus such as the dentate gyrus and cornu ammonis (CA) fields 1–4 in PTSD. The aim of the present study was to examine the hypothesis that volume of the dentate gyrus, a region putatively involved in distinctive encoding of similar events, is smaller in individuals with PTSD versus trauma-exposed controls. Ninety-seven recent war veterans underwent structural imaging on a 3T scanner and were assessed for PTSD using the Clinician-Administered PTSD Scale. The hippocampal subfield automated segmentation program available through FreeSurfer was used to segment the CA4/dentate gyrus, CA1, CA2/3, presubiculum, and subiculum of the hippocampus. Results showed that CA4/dentate gyrus subfield volume was significantly smaller in veterans with PTSD and scaled inversely with PTSD symptom severity. These results support the view that dentate gyrus abnormalities are associated with symptoms of PTSD, although additional evidence is necessary to determine whether these abnormalities underlie fear generalization and other memory alterations in PTSD.     

Species differences in the projections from the entorhinal cortex to the hippocampus

Both differences and similarities exist between mammalian species in the projections from entorhinal cortex to the hippocampal formation. In most species, layer II cells of the entorhinal cortex project to the dentate gyrus, and they terminate in the outer two-thirds of the molecular layer of the dentate gyrus. The axons from layer III cells project bilaterally to areas CA(1) and CA(3) of the hippocampus, terminating in the stratum lacunosum moleculare. We have analyzed these projections in mice, and in general, the entorhinal cortex-to-hippocampus projections are similar to those in rats. Axons from layer II neurons terminate in the outer and middle thirds of the molecular layer of the dentate gyrus, and axons from layer III neurons terminate bilaterally in the stratum lacunosum moleculare of areas CA(1) and CA(3), and in the molecular layer of the subiculum. However, in contrast to rat, mouse entorhinal cortex neurons do not appreciably project to the contralateral dentate gyrus. Most species, including mice, show a similar topographical organization of the entorhinal-hippocampal projections, with neurons in the lateral part of both the lateral and medial entorhinal cortex projecting to the dorsal part or septal pole of the hippocampus, whereas the projection to the ventral hippocampus originates primarily from neurons in medial parts of the entorhinal cortex.     

Distribution of substance P reveals a novel subdivision in the hippocampus of parasitic South American cowbirds

Parasitic cowbirds monitor potential hosts' nests and return to lay when appropriate, a task that is likely to involve spatial recall. Seasonal and sexual behavioral variations in the cowbirds correlate with anatomical changes in the hippocampal formation. During the breeding season, parasites have larger hippocampal formations than nonparasites. In parasitic species in which females alone perform nest bookkeeping, females have larger hippocampal formations than males. We investigated the distribution of the neuropeptide substance P (SP) in three sympatric cowbirds: two obligate parasites (shiny cowbird and screaming cowbird) and one nonparasite (bay-winged cowbird). Distribution of SP was similar to that in other songbirds, except for a previously undescribed field of dense SP-rich terminals within the hippocampus that we call the hippocampal SP terminal field (SPh). We found robust species differences in the volume of this new area, measured relative to the remainder of the telencephalon. SPh was largest in the generalist parasite (shiny cowbird) and smallest in the nonparasitic species (bay-winged cowbird). In the specialist parasite (screaming cowbird), SPh was smaller than in the generalist parasite but larger than in the nonparasitic species. SPh overlaps with two subdivisions described in the pigeon that have been related to the mammalian dentate gyrus and subiculum. The area containing SPh receives a major input from the lateral mammillary nucleus, which is probably the avian equivalent of the mammalian supramammillary nucleus (SUM), the main source of extrinsic SP input to mammalian hippocampus. SPh may be the termination of a pathway homologous to the SP-rich projection from SUM to the hippocampus in mammals.     

The distribution of chromogranin A-like immunoreactivity in the human hippocampus coincides with the pattern of resistance to epilepsy-induced neuronal damage

The distribution of chromogranin A-like immunoreactivity in the hippocampus of adult humans who were free of neurological disease was examined by immunohistochemical methods. Immunoreactivity was restricted to the cytoplasm of certain neuronal populations, most notably the mossy fibers of denate granule cells (and a subset of their perikarya), and the perikarya of pyramidal cells of the cornu Ammonis 2 (CA2) sector. Additionally, staining was observed in neurons in the stratum oriens, a population of neurons at the periphery of the CA4 sector, scattered, probably short-axon perikarya in the CA1 sector, and fibers in the perforant path and the molecular layer of the dentate gyrus. Pyramidal neurons in the CA1 and CA3 sectors were not immunoreactive. The two prominently immunoreactive neuronal populations, CA2 pyramids and dentate granule cells, are those spared in human and experimental epileptic brain damage, whereas CA1 and CA3 pyramids, lacking chromogranin, are characteristically destroyed in this condition. The known activities of chromogranin in the periphery as a calcium-binding protein and as a precursor of active peptides (autocrine inhibitory modulators) suggest that its distribution in the hippocampus may help to explain the observed pattern of resistance to epileptic brain damage.     

Effects of corticosterone treatment and rehabilitation on the hippocampal formation of neonatal and adult rats. An unbiased stereological study

Elevations in the plasma levels of glucocorticoids are associated with cognitive impairments that have been ascribed to loss of neurons in the hippocampal formation. However, recent studies have strongly challenged this view. In order to clarify this issue, we have employed for the first time the optical fractionator and the Cavalieri principle, two unbiased stereological tools, to estimate respectively the total number of neurons and the volumes of the main subdivisions of the hippocampal formation of rats submitted to corticosterone treatment for different periods, either neonatally or in adulthood. A significant reduction in the number of neurons and in the volumes of the layers of the dentate gyrus and CA3 hippocampal field was found in rats exposed to glucocorticoids in the neonatal period; furthermore, animals treated with corticosterone from birth until 180 days of age had also a reduction in the volume of the stratum radiatum of the CA1 hippocampal field. Conversely, when the exposure occurred only during adulthood, no significant neuronal loss was observed, but there were significant reductions in the volume of layers in the dentate gyrus and CA3 hippocampal field. To search for signs of structural recovery, we incorporated a group of rats submitted to corticosterone treatment during the neonatal period in which the hormonal conditions were restored thenceforth. In this group we found a significant increase in the volume of the molecular layer of the dentate gyrus when compared with rats that were kept under corticosteroid treatment. In conclusion, these data provide a sound structural basis for the cognitive deficits observed during, and following, exposure to increased levels of glucocorticoids.     

Prion disease causes less severe lesions in human hippocampus than other parts of brain

Aim:  The hippocampus can be very sensitive to damage in the scrapie-infected mouse, a well-established animal model of prion diseases. Terminally ill scrapie-infected animals exhibit nearly complete loss of cornu ammonis (CA) 1 pyramidal neurons, but few studies have focused on the neuropathological lesions of the human hippocampus in autopsied brain tissue; in particular, few findings on differences in severity of pathology between the hippocampal and parahippocampal formations have been obtained. The aim of the present paper is to evaluate the human hippocampus of prion disease through neuropathological examination.
Methods:  A systemic, detailed neuropathological study throughout the subdivisions of the hippocampus was carried out in 23 autopsied cases of prion diseases. Prion protein immunohistochemistry was performed in serial brain sections to determine the topography of prion deposits.
Results:  Compared to lesions in other brain regions, hippocampal lesions were mild, despite numerous prion deposits. The distribution of prion deposits did not appear to be correlated with neuropathological changes. The present findings differed from the hippocampal pathology observed in scrapie-infected mice. In addition, differences in neuropathological severity were observed within the hippocampal formation.
Conclusion:  The human hippocampus may be protected from the neurotoxic effects of prion deposits.     

Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer's disease

To explore more fully the relationship between neuronal death and neurofibrillary degeneration, unaffected neurons, intracellular neurofibrillary tangles (i-NFT) and extracellular NFT (e-NFT) in 22 patients with late-onset sporadic Alzheimer's disease (AD) were morphometrically evaluated in eight subdivisions of the hippocampal cortex, using the Gallyas hematoxylin-eosin stain. The subdivisions examined included CA4, CA3, CA2, CA1 (CA: cornu ammonis), prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). The unaffected neuron density was significantly lower and both i-NFT and e-NFT densities were significantly higher in subdivisions other than CA4 and CA3 in AD patients compared with those in the aged controls. Unaffected neuron density was significantly, inversely correlated with e-NFT density and with total NFT density in all subdivisions except for PRE in AD patients. Especially in CA2, CA1, PRO and ENT, there were strong correlations between the neuron density and these NFT densities. Both unaffected neuron and e-NFT densities in CA1 and ENT were significantly correlated with the disease duration. The i/e-NFT ratio, an index of the degree and/or rate of progress of neuronal death via neurofibrillary degeneration, showed the lowest value in ENT in AD patients. The findings suggest that neuronal death via neurofibrillary degeneration starts earliest and/or most rapidly progresses in ENT. Furthermore, the i/e-NFT ratios in both ENT and CA1 were significantly correlated with the disease duration, suggesting that the neuronal death pattern in the two subdivisions parallels disease progression.     

Protein malnutrition differentially alters the number of glutamic acid decarboxylase-67 interneurons in dentate gyrus and CA1-3 subfields of the dorsal hippocampus

In 30- and 90-day-old rats, using immunohistochemistry for glutamic acid decarboxylase 67 (GAD-67), we have tested whether malnutrition during different periods of hippocampal development produces deleterious effects on the population of GABA neurons in the dentate gyrus (DG) and cornu Ammonis (CA1-3) of the dorsal hippocampus. Animals were under one of four nutritional conditions: well-nourished controls (Con), prenatal protein malnourished (PreM), postnatal protein malnourished (PostM), and chronic protein malnourished (ChroM). We found that the number of GAD-67-positive (GAD-67+) interneurons was higher in the DG than in the CA1-3 areas of both Con and malnourished groups. Regarding the DG, the number of GAD-67+ interneurons was increased in PreM and PostM and decreased in ChroM at 30 days. At 90 days of age the number of GAD-67+ interneurons was increased in PostM and ChroM and remained unchanged in PreM. With respect to CA1-3, the number of labeled interneurons was decreased in PostM and ChroM at 30 days of age, but no change was found in PreM. At 90 days no changes in the number of these interneurons were found in any of the groups. These observations suggest that 1) the cell death program starting point is delayed in DG GAD-67+ interneurons, and 2) protein malnutrition differentially affects GAD-67+ interneuron development throughout the dorsal hippocampus. Thus, these changes in the number of GAD-67+ interneurons may partly explain the alterations in modulation of dentate granule cell excitability, as well as in the emotional, motivational, and memory disturbances commonly observed in malnourished rats.     

Correlations Between Granule Cell Dispersion, Mossy Fiber Sprouting, and Hippocampal Cell Loss in Temporal Lobe Epilepsy

PURPOSE: Correlations between granule cell dispersion (GCD), collateral mossy fiber (MF) sprouting, and hippocampal cell loss were studied to assess the relation between GCD and synaptic reorganization in the dentate gyrus of patients with epilepsy. METHODS: Twenty specimens from patients with medically intractable temporal lobe epilepsy (TLE) were studied along with two control specimens. GCD was considered to be present when the stratum granulosum was wider than 120 microm, the close apposition between the granule cell (GC) soma was lost, and GCs were scattered in the molecular layer (ML). Patterns of MF sprouting were differentiated as wide or narrow according to the area of neo-Timm's staining in the ML. GC loss and volumetric cell-density decreases in the different subfields were assessed. RESULTS: MF sprouting was observed in 16 (80%) and GCD in nine (45%) cases. A significant correlation was found between MF sprouting and cell loss in all the subfields except the cornu Ammonis field 2 (CA2). A wide band of MF sprouting was associated with severe cell loss. Cases with GCD had a wide band of MF sprouting and also a higher degree of cell loss than cases without GCD. CONCLUSION: GCD is associated with a specific pattern of MF sprouting, but cell loss was found to be a major determinant for MF reorganization.     

Sema3C and netrin-1 differentially affect axon growth in the hippocampal formation

The interaction between outgrowing neurons and their targets is a central element in the development of the afferent and efferent connections of the hippocampal system. This requires that axonal growth cones recognize specific guidance cues in the appropriate target area. At present, little is known about the mechanisms that determine the lamina-specific termination of hippocampal afferents. In order to understand the role of different guidance factors, we analyzed the effects of Sema3C and Netrin-1 on explants from the entorhinal cortex, dentate gyrus, cornu ammonis regions CA1 and CA3 and medial septum in a collagen coculture assay. Our observations suggest that both semaphorins and netrin play important roles in the neuron-target interactions in the hippocampal system. Sema3C is involved in the control of the ingrowth of the septohippocampal projection. We also show that netrin-1 is involved in attracting commissural neurons from dentate gyrus/hilus and CA3 to their target area in the contralateral hippocampus.     

Neurons and neurofibrillary tangles in the hippocampal cortex in familial and sporadic Alzheimer's disease

Hippocampal pathology was morphometrically studied in six early onset familial Alzheimer's disease (FAD) patients and the results were compared with six early onset sporadic Alzheimer's disease (SAD) patients. Unaffected neurons, intracellular neurofibrillary tangles (I-NFT) and extracellular neurofibrillary tangles (E-NFT) were evaluated on the same sections in eight subdivisions of the hippocampal cortex, using Gallyas technique modified by a direct application of hematoxylin and eosin stain (Gallyas-HE stain). The subdivisions were CA4, CA3, CA2, CA1, prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and entorhinal cortex (ENT). Unaffected neuron densities in CA2, CA1 and PRE in FAD were significantly lower than those in SAD. In contrast, in ENT the unaffected neuron density in FAD was greater than that in SAD, but the difference was not significant. Extracellular neurofibrillary tangle densities in the subregions, other than ENT in FAD, were greater than those in SAD, while the E-NFT density in ENT in FAD was lower than that in SAD. Neurofibrillary tangles (I-NFT plus E-NFT) densities in CA3, CA2, CA1 and PRO in FAD were significantly greater than those in SAD. These data suggest that cornu ammonis is affected more severely than is the ENT in early onset FAD. These findings indicate that hippocampal pathology in early onset FAD may be qualitatively as well as quantitatively different from that in early onset SAD.     

Distribution of corticosteroid receptors in the rhesus brain: relative absence of glucocorticoid receptors in the hippocampal formation.

Chronic stress has been associated with degenerative changes in the rodent and primate hippocampus, presumably mediated in part via neuronal glucocorticoid receptors (GRs). In the rat brain, GRs are widely distributed and are particularly dense in the hippocampus. The distribution of GRs in the primate brain, however, has not been fully characterized. In this study, we used in situ hybridization histochemistry and immunohistochemistry to map the distribution of GR mRNA and GR protein, respectively, in adult rhesus monkeys (Macaca mulatta). In contrast to its well established distribution in the rat brain, GR mRNA was only weakly detected in the dentate gyrus (DG) and Cornu Ammonis (CA) of the macaque hippocampus, whereas it was abundant in the pituitary (PIT), cerebellum (CBL), hypothalamic paraventricular nucleus (PVN), and, to a lesser extent, the neocortex. Immunohistochemical staining indicated a very low density of GR-like immunoreactive cells within the macaque hippocampal formation in contrast to the high density observed within the PVN, prefrontal and entorhinal cortices, and cerebellar cortex. Relative to the low level of GR, mineralocorticoid receptor (MR) mRNA and protein expression were abundant within the DG and CA of the rhesus monkey hippocampal formation. These results indicate that, in the primate, neocortical and hypothalamic areas may be more important targets for GR-mediated effects of glucocorticoids than the hippocampus. Alternatively, it is also possible that glucocorticoid effects are mediated through the MRs present in the hippocampal formation.