Spatial information is important for many species to survive in an environment. However, the environment is variable, and then animals have to adapt to the new environment by using information derived from past experience. Many previous studies have shown that the is an important brain structure for learning and memory. It is well established that hippocampal neurons encode specific locations in the environment, which is called as place cells. We have investigated plasticity of spatial correlates of rat place cells when reward-place associations are altered. In this symposium, we will show some examples of place cells whose firing changes when rats learn a novel place task. Place cell activities were recorded during learning sessions of the place task in which rats were rewarded at two reward areas on an open field when they shuttled between these two areas. Rats learned the task well, and showed regular shuttling behavior between the two reward areas in several sessions. Some of the place cells recorded changed spatial firing patterns during learning. Changes of the trajectories and spatial firing patterns as a function of the learning session were highly correlated. Furthermore, spatial firing patterns of some place cells of rats that had learned the task changed when reward-place association was changed in the same task. These results suggest that hippocampal place cells have an important roll in spatial learning, and contributes to selection of an efficient route to a goal. [Jpn J Physiol 55 Suppl:S41 (2005)]

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This study was performed to anatomically illustrate the living canine in three-dimensions (3D), and to evaluate its relationship to surrounding brain structures. Three normal beagle dogs were scanned on a MR scanner with inversion recovery segmented 3D gradient echo sequence (known as MP-RAGE: Magnetization Prepared Rapid Gradient Echo). The MRI data was manually segmented and reconstructed into a 3D model using the 3D slicer software tool. From the 3D model, the spatial relationships between and surrounding structures were evaluated. With the increased spatial resolution and contrast of the MPRAGE, the canine was easily depicted. The reconstructed 3D image allows easy understanding of the hippocampal contour and demonstrates the structural relationship of the to surrounding structures in vivo.

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Zinc in the was studied by the sulfide silver method at 5,10,15, and 30 min after administration of 200 mg/kg oxine in rats. Specimens obtained at the same stages were also investigated electron microscopically.
In rats at 5 min after the oxine administration, areas with a normal positive reaction for zinc, h3-h5 the of the adjacent to the stratum pyramidale of the stratum radiatum and stratum multifome of the dentate gyrus, gave a negative reaction. At 15 min after the administration, a slightly positive reaction was noted, and an intense positve reaction was observed at 30 min after the administration.
Electron microscopy revealed a marked decrease of synaptic vesicles in the mossy fiber endings of the rats at 5 min after the oxine administration. At 15 min after the administration, the synaptic vesicles in the mossy fiber endings were considerably increased. At 30 min after the administration, synaptic vesicles were densely accumulated within the endings as in normal animals.

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1-Bromopropane (CH₃CH₂CH₂Br 1-BP) is a newly introduced substitute for specific chlorofluorocarbons whose production was prohibited because of depletion of ozone layers, and is mainly used for degreasing agents and spray adhesives. Although case studies in the USA and China have demonstrated that 1-BP could adversely affect the human nervous system, the underlying mechanism for the effects of 1-BP inhalation exposure on the CNS has not been understood. We investigated the effects of 1-BP exposure on the CNS using different models of exposure. 1-BP potentiated GABA but inhibited ACh responses in Xenopus oocytes expressing GABA_A and nicotinic ACh receptors, respectively, and enhanced recurrent inhibition in the rat hippocampus. On the other hand, hippocampal disinhibition was observed in a concentration-dependent manner (200–1500 ppm) after chronic inhalation of 1-BP in the rats and, at the highest concentration of 1-BP inhalation, epileptic potentials were evoked in the dentate gyrus. Moreover, prenatal exposure to 1-BP vapor resulted in enhanced stimulation/response (S/R) curve of population spikes in the CA1 area of PND 11-15 rats and reduced S/R curve of field excitatory postsynaptic potentials in the CA1 area in adults (6-8w). These results suggest that 1-BP inhalation exposure disrupts neuronal excitability of the . [J Physiol Sci. 2006;56 Suppl:S22]

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The of the monkey (Macaca fuscata) was investigated by electron microscopy. Our attention was directed to the fine structure of the pyramidal cells in CA 3, CA 4 and of the mossy fiber endings. In addition to ordinary cell organelles, coated vesicles and subsurface cisterns were frequently observed in the pyramidal cells. We could find the initial segment of the axon of the pyremidal cells in CA 3 and moreover on the surface of it we could detect mossy fiber endings as well as Gray's type II synapses. The structure of the mossy fiber endings was fundamentaly similar to that of other mammalia. Pyramidal cells were frequently covered with mossy fiber endings, some of which terminated on neuronal somata as axo-somatic synapses. We observed dark mossy fiber endings which contained many dark synaptic vesicles and mitochondria. We also demonstrated a feature of protrusion of dendritic spines into the mossy fiber endings by serial sections. Small axo-somatic, axo-dendritic and axo-spinodendritic synapses were observed in the hilus fascia dentatae, CA 4, and in the strata radiata and pyramidale of CA 3. We classified these into two types, S and F, according to the shape of the synaptic vesicles they contained. By using Timm's sulfide-silver method under electron microscopic level dark precipitations due to the presence of zinc were found in preterminal regions of both ordinary and dark mossy fiber endings. Their distribution seemed to be restricted to synaptic vesicles as they were not seen in mitochondria. We also found dark precipitations in the small preterminal boutons distinct from mossy fiber endings.

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Our previous study showed that mice fed a soft diet after weaning had reduced synaptic connections in the and impaired spatial learning ability after 3 months of age. We hypothesized that soft-diet feeding during development reduced levels of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, resulting in lower synaptic densities in this region. Male pups of C57BL/6 mice were fed either a solid (hard-diet group) or powdered diet (soft-diet group), starting at weaning. Expression of BDNF protein in the hippocampus and cerebral cortex was evaluated quantitatively with enzyme-linked immunosorbent assay (ELISA) at 1, 3 and 6 months of age. Reduction in BDNF protein levels due to soft diet was detected markedly in the hippocampus of 3- and 6-month-old mice. On the other hand, a soft diet showed no significant effect on BDNF content in the cerebral cortex throughout the ages investigated. Immunohistochemistry of in 3-month-old mice revealed that intensities of BDNF immunoreactivity in the dentate gyrus granule cell layer and CA1 and CA3 pyramidal cell layers appeared diminished in mice fed the soft diet compared with mice fed the hard diet. These results indicate that insufficient mastication activity during development reduces BDNF protein levels in the hippocampus and influences synaptic plasticity in this region.

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To facilitate improvement of investigations on the distribution of mossy fibers in the , a method is described using Timm's stained preparations after methacrylate embedding with the hydrophilic resin, Quetol 523M. Fixation with a mixture of formaldehyde and glutaraldehyde yielded satisfactory staining results and good structural preservation. During the course of histochemical experiments employing Timm's staining, examinations revealed that sulfide silver reaction products were consistently present in both the mossy fibers themselves and their terminals associated with the dendrites of pyramidal cells in tissue sections of 1-2μm in thickness. The results obtained also revealed that variations of the mossy fiber system occurred in the neurological mutant mouse dreher (dr). The bundles of mossy fibers forming the intrapyramidal synaptic field may be considered to reflect genotype-dependent differences in the mutation. The present method is adequate for allowing the histochemical demonstration of mossy fibers and their giant boutons by light microscopy.

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Copper (Cu) is an essential element for life, however, is toxic at excessive doses, whereas exposure to ethanol (EtOH) has been known to cause morphological changes, degeneration and neuronal loss in central nervous system (CNS). In this study, the effect of overdose co-exposure to Cu and EtOH on dentate gyrus was investigated in rats. Analysis of apoptotic cell death on the basis of TdT-mediated dUTP nick end labeling (TUNEL) assay revealed that the rate of apoptosis was increased by 1.84 folds in treated group in comparison to that in controls (p < 0.0001). Analysis of cell proliferation on the basis of 5-bromo-2'-deoxy-uridine labeling assay, on the other hand, revealed a 1.49 fold increase in treated group when compared to controls (p < 0.006). Total number of granule cells in dentate gyrus of each group was estimated using the optical fractionator method. The results showed that mean granule cell number in dentate gyrus was 4.64% lower in treated group than that in control group, but this difference was not statistically significant (p > 0.05). These results suggest that the apoptotic effect of overdose Cu and EtOH on granule cells of dentate gyrus may be counterbalanced by the co-induced cellular proliferation, thereby maintaining the total granule cell number unaltered.

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Previously, multi-lectin positive spherical shaped deposits were detected in the of degenerative demented and schizophrenic brains and reported they possessed some possibility as a predominant tool of postmortem diagnosis, more detected in schizophrenia cases than age-matched control cases. Multi-fluorescent immunohistochemical and lectin histochemical method and immuno electron microscope method were performed on 51 forensic autopsied brains containing 16 cases of schizophrenia. In multi-fluorescent staining, partial disrupted nucleus with decreased staining properties by mean of SYBR green were detected, and lectin and single strand DNA were co-stained in the portion of partial disrupted nucleus. In immuno electron microscope method, lectin positive structures were also detected in the portion of partial disrupted nucleus. These neurons were suspected in the process of apoptosis by their distinguishable features. Some experimental studies were reported that a kind of therapeutic products of major tranquillizers induced neuron apoptosis in dentate gyrus. As the lectin positive spherical shaped deposits were detected in not only 5 schizophrenia cases without drug treatment but also in 11 schizophrenia cases with drug treatment in this study, they might be detected as the intrinsic pathological change of schizophrenia. The lectin positive spherical shaped deposits detected in the were suspected as the histopathological marker of the postmortem diagnosis for schizophrenia. Further examination for specifying group of neurons detected them in and initiated apoptosis are necessitated. J. Med. Invest. 57: 183-190, August, 2010

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Sclerosis of the cornu Ammonis or Ammon's horn sclerosis (AHS) is an “often-described, yet hitherto enigmatic phenomen” as Spielmyer put it in 1927. It has been found in cases with ischemia, anoxia or hypoglycemia and in more than half of the epileptic brains examined at autopsy. Various theories about its pathogenesis have been propunded. Among them, the “Pathoklise” theory of the Vogts and the vascular theory of Spielmeyer and his associates were prevailing until recently. In 1953, two articles were published to contribute to the pathogenesis of ictal automatism (a type of complex partial or temporal lobe seizures). One is the incisural sclerosis theory by Penfield and his associates and the other is the Ammon's horn sclerosis theory by Sano and Malamud. The former authors described a diffuse sclerosis of the infero-mesial temporal structures without, however, specifically relating it to AHS. They considered it was the result of localized anoxia of that portion of the brain caused by incisural herniation occurring during parturition. Sano and Malamud maintained that AHS is a result of convulsions, a distinct scar adjacent to which epileptogenic foci may develop in the course of time to cause ictal antomatism. The latter theory was corroborated by Sano, Falconer and others. Falconer expanded the theory to the assertion that not only ictal automatism but other types of intractable epilepsy may be due to “mesial temporal (Ammon's horn) sclerosis”. The most recent development in the pathogenesis of AHS is the excitotoxicity theory. Namely, AHS is caused by excessive excitation of neurons, probably by putative excitatory neurotransmitters, especially, glutamate. For this theory, there is a significant body of evidence. The problem of AHS, an old research subject and a matter of long-lasting controversy, has now been updated and become one of the newest topics in the field of experimental neurobiology.

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The of monkey was studied by sulfide silver technique. Intense positive reaction to this method was found in the stratum radiatum of h₃, h₄ and h₅ of the hippocampus, as well as the stratum multiforme of the fascia dentata. All these areas correspond to the endings of mossy fibers at the apical dendrite of pyramidal cells in the .

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従来、健忘症患者の報告から、海馬体が記憶機能に重要な役割を果たすとされてきた。さらに、人間以外の霊長類やラットによる多くの実験研究から、海馬体のみならず、その周辺の皮質構造も記憶機能に関与してきていることが指摘されてきた。すなわち、記憶障害の原因として海馬体だけでなく、嗅周皮質、内嗅皮質および海馬傍回等の役割も重視されてきた。本研究では、嗅周皮質に限局された脳硬塞のある患者に、種々の神経心理学的精査を行ない、その病変がもたらした神経心理学的機能障害を検討し、嗅周皮質の役割について考察することを目的とした。当該患者が臨床的に安定した病態を示してから、脳磁気共鳴画像により、病巣の同定を行なったころ、左の嗅周皮質に病巣が認められた。標準化された神経心理学的検査を行なったところ、簡易精神機能スケール（MMSE）では問題を認めず、知能（WAIS-R）は平均水準であった。失語、失行、失認に関する検討でも問題は認められなかった。ウエクスラー記憶尺度（WMS-R）では、全体としての記憶指数は平均的であった。しかし、その下位検査のプロセス分析を行なったところ、有関連単語ではなく、無関連単語の対連合記憶学習のみ、困難であることが示された。さらに、さまざまな対連合記憶学習課題（図形と図形の対、色と色の対、図形と色の対、単語と色の対、単語と単語の対）を施行して、精査を行なったところ、言語性および非言語性課題においてともに、無関連の対連合記憶学習が困難であることが示された。また、言語課題においては、提示によるモダリテイの差異について検討したところ、聴覚的な提示と視覚的な提示で異ならず、いずれも、無関連の対連合記憶学習のみが困難であることが示された。これらの結果から、本症例は選択的に無関連対連合記憶学習の障害をきたしていることが明らかとなった。このことは、嗅周皮質が、新しい刺激と刺激との関連の記憶の形成に関わることを示唆している。嗅周皮質はモダリテイにかかわらず、記憶過程で、新しい連合形成と検索に重要な役割を果たしているのかもしれない。

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The of mouse, rat, guinea pig, rabbit, cat, dog, goat and monkey were seen by sulfide silver technique. Intense positive reaction to the this method was found in the stratum radiatum of h₃, h₄ and h₅ of the hippocampus, as well as the stratum multiforme of the fastia dentata. All these areas corespond to the endings of mossy fibers at the apical dendrit of pyramidal cells in the . No histochemical reaction of zinc was observed in the brains of rat of newborns up to 10 day after birth. The showed a slight reaction on and after the 11 day of life and the zinc contents of these areas reacted almost normal level about 2 weeks after birth.
Histochemical evidence has been observed by the sulfide silver method that the zinc distributed in the region becomes temporarily undemonstrable for a certain brief period (1-3 hours) following administration of dithizone (200 mg/kg).
Sections taken at 1.5 hours after administration of dithizone (5 mg/kg) showed positive reaction by the sulfide silver method. During the first three hours following the administration of dithizon (10 mg/kg-300 mg/kg) the remains unstained.
The distribution of zinc in the of the rat was changed by circadian rhythm.

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The NMDA receptor non-competitive antagonist, [³H] MK-801, was used as a ligand for an autoradiographic study to determine the effects of lead on NMDA receptor in rat brain. Adult male rats were given lead acetate, 100 mg/kg, or sodium acetate, 36 mg/kg (control), by i. p. for 7 days. Lead levels were detected in blood (41.1μg/dl) and brain (16.7-29.4μg/g). Concentrations of lead in various brain regions did not differ. [³H] MK-801 binding was heterogeneous throughout the brain with the following order of binding densities : >cortex>caudate-putamen>thalamus>brainstem. Lead exposure caused a decrease in [³H] MK-801 binding to NMDA receptors in the including CA2 stratum radiatum, CA3 stratum radiatum and presubiculum, and in the agranular insular, cingulate, entorhinal, orbital, parietal and perihinal areas of cerebral cortex. In another experiment, female rates were exposed pre-and post-natally from the 4th±1 post cconception day with 1, 000 ppm lead in their drinking water. This treatment continued after weaning. No effects of lead on [³H] MK-801 binding were found at postnatal day (PM) 28. However, lead caused a significant increase in [³H] MK-801 binding in the hippocampus including CA1 and CA2, and in the occipital and temporal cortical areas at PN 56 and at PN 112. Increases in [³H] MK-801 binding were also found in entorhinal cortex and dentate gyrus at PN 112. The is a critical neural structure for learning and memory processes, whereas cortical and subcortical regions are involved in the modulation of complex behavioral processes. NMDA receptors have been shown to play a key role in synaptic plasticity underlying learning and memory. Therefore, lead-induced alterations of ligand binding to NMDA receptors in the and cortical areas may play a role in lead-induced neurotoxicity.

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We investigate some noise effect on a neural network model proposed by Araki and Aihara for the memory recall of dynamical patterns in the hippocampus and the entorhinal cortex; the noise effect is important since the release of transmitters at synaptic clefts, the operation of gate of ion channels and so on are known as stochastic phenomena. We consider two kinds of noise effect due to a deterministic noise and a stochastic noise. By numerical simulations, we find that reasonable values of noise give better performance on the memory recall of dynamical patterns. Furthermore we investigate the effect of the strength of external inputs on the memory recall.

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The localization of ouabain-sensitive, K⁺-dependent p-nitrophenylphosphatase (K⁺-NPPase) activity, a part of the reaction of the Na⁺-K⁺-ATPase complex, was ultracytochemically investigated in the rat called substantia gelatinosa cerebri. Microslicer sections of the fixed with a mixture of 0.25% glutaraldehyde and 1% paraformaldehyde for 30 min were incubated in the medium for K⁺-NPPase.
In the light microscopic observations, the most abundant reaction products were present in the stratum moleculare of the . Electron microscopically, K⁺-NPPase activity was demonstrated on the axolemma, neurofilamentous structures in the axoplasm and synaptic plasma membrane. These activities were distinctly decreased with addition of 10 mM ouabain or substitution of Na⁺ for K⁺. Additionally, ouabain-insensitive, K⁺-independent p-NPPase activity was observed on the mitochondria, nuclear envelope and endoplasmic reticulum. Neurotubules did not show any K⁺-NPPase activity.

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To investigate the effects on the central nervous system of subchronic exposure to 1-bromopropane (1-BP), which is a substitute for chlorofluorocarbons, we measured the hippocampal excitability of 1-BP-treated rats electrophysiologically. Male Wistar rats were exposed to 1-BP for 6-h in a day in an exposure chamber (1,500 ppm) for 4 wk. After the 1-, 3- and 4-wk inhalation, field excitatory postsynaptic potentials (fEPSPs), population spikes (PSs), fEPSP/spike (E/S) curve, paired-pulse profiles of fEPSP slopes and PS amplitudes recorded from CA1 pyramidal neurons, and dentate granule cells of the hippocampal slice obtained from the rats were analyzed. In 1-BP treated rats, E/S potentiation and a lower subthreshold of PSs were observed in the dentate gyrus (DG) after the 3 and 4-wk inhalation. Paired-pulse inhibition was reduced at 5-50 ms in the CA1 and at 5-20 ms in the DG after all of the inhalation. These changes were not associated with paired-pulse inhibition of fEPSPs. In the DG, the paired-pulse inhibition at the short interpulse intervals in rats exposed to 1-BP was pronounced by an application of A type gamma aminobutyric acid (GABA) receptor agonist pentobarbital. Impaired paired-pulse inhibition of granule cells at the short interpulse intervals was recovered after the application of N-methyl-D-aspartate (NMDA) type glutamate receptor antagonist DL-2-amino-5-phosphonopentanoic acid. Convulsing rats observed after the 4-wk inhalation exhibited multiple PSs in the DG, and their second component was abolished by an application of this antagonist. Inhalation of 1-BP increased the neuronal excitability in the hippocampal CA1 and the DG. The hyperexcitability of the granule cells in the DG was at least due to an over-activation of NMDA receptors.

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