Y Kuroda

Tokyo Metropolitan Institute, Edo, Tōkyō, Japan

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Publications (75)139.85 Total impact

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    ABSTRACT: In the present study, both potentiation and depression of the synaptic response were induced in hippocampal CA1 neurons by systematically varying the frequency of low frequency afferent stimulation (LFS) between 0.5 and 25 Hz and the pulse number between 40 and 1000. The input-response relationship for CA1 synapses showed that LFS at a higher frequency or with a smaller pulse number increased the magnitude of potentiation of the synaptic response by increasing the contribution of N-methyl-D-aspartate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs) to induction of potentiation. One possible mechanism for this bidirectional plasticity was that specific patterns of LFS differentially activate a uniform receptor population in producing depression or potentiation of synaptic responses. However, a pharmacological study indicated that, despite their opposite effects, both the synaptic depression induced by LFS at 1 Hz and the synaptic potentiation induced by LFS at 10 Hz were triggered by co-activation of NMDARs and mGluRs at CA1 synapses. We suggest that activation of protein kinase C or inositol-1,4,5-trisphosphate receptors, both coupled to group 1 mGluRs, is involved in the bidirectional synaptic plasticity induced in hippocampal CA1 neurons by 1-10 Hz LFS.
    Neuroscience 03/2010; 168(2):346-58. · 3.12 Impact Factor
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    ABSTRACT: We previously established a primary culture system of the accessory olfactory bulb (AOB) to investigate the functional roles of individual types of neuron in pheromonal signal processing. However, the detailed characteristics of cultured AOB neurons were not yet apparent. In the present study, we address the cytological aspects of cultured AOB neurons using immunocytochemical staining methods. Cultured AOB neurons were compared with cultured main olfactory bulb (MOB) neurons in neuronal composition, maturational time course, and cell size. The number of total neurons, measured by microtubule-associated protein 2 (MAP2) immunostaining, progressively decreased, and glutamic acid decarboxylase positive (GAD+) interneurons were scarcely changed in their number in both AOB and MOB cultures over the culture periods. In contrast, the number of tyrosine hydroxylase positive (TH+) neurons in AOB cultures showed a slight, but significant, increase over time in culture, while those in MOB cultures remarkably decreased. The numbers of total neurons and GAD+ neurons were significantly greater in AOB cultures than in MOB cultures at all investigated time points. However, the numbers of TH+ neurons were lower at 7 days in vitro (DIV) and greater at 21 DIV in AOB cultures than in MOB cultures. The somatic sizes of all types of neurons at 14 DIV were significantly larger in AOB cultures than in MOB cultures. Furthermore, the frequency distributions of somatic sizes of total, GAD+, and TH+ neurons were significantly different between AOB and MOB cultures. These subtle differences in vitro may reflect in vivo differences between the AOB and MOB.
    Anatomy and Embryology 01/2005; 209(2):129-36. · 1.42 Impact Factor
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    ABSTRACT: The characteristics of functional changes of GABAergic synapses between cultured rat cortical neurons were observed by monitoring intracellular calcium level ([Ca2+]in) during development in vitro. After 5 days in vitro (DIV), cultured cortical neurons spontaneously exhibited synchronous oscillatory changes in [Ca2+]in, which were derived from synaptic activity. Exposure to bicuculline, antagonist of gamma-aminobutyric acid (GABA)(A) receptors, caused a marked decrease in the frequency of [Ca2+]in oscillations at 7-20 DIV. Although the frequency of spontaneous oscillations increased during this culture period, the ratio of the decrease in the frequency following bicuculline treatment did not significantly change. Thereafter, to investigate the detailed morphological changes of GABAergic synapses during development in vitro, the cultured neurons were immunostained with antibodies to glutamic acid decarboxylase (GAD), synaptophysin and GABA(A) receptor and were observed under a confocal laser microscope. Most of the GAD-positive puncta colocalized with synaptophysin-positive puncta and were opposed to GABA(A) receptor-positive structures. The images of GAD-positive puncta were reconstructed from the confocal three-dimensional data to analyze their number, volume, and surface area. The number of these puncta increased with culture time at 7-20 DIV. Although the volume of individual GAD-positive puncta did not significantly change, the surface area decreased in a time-dependent manner over the culture period. This system that we developed enabled us to investigate in detail the morphological and functional changes of GABAergic synapses during neuronal development.
    Developmental Brain Research 10/2004; 152(2):99-108. · 1.78 Impact Factor
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    ABSTRACT: Synapse plasticity, in particular, formation of new synapses, plays crucial roles in learning and memory. We have developed a convenient assay system for measuring the number of newly formed synapses between cultured rat cerebrocortical neurons using the multisite fluorometry system of intracellular calcium. We found that cultured neurons exhibited spontaneous oscillatory changes in intracellular calcium levels and that the frequency of the oscillation was strongly correlated with synaptic density. Combined with immunohistochemical studies, this assay system enables us to study the molecular mechanism of synapse formation, in particular, the involvement of ecto-protein kinase. Other applications of the assay system are discussed here.
    Folia Pharmacologica Japonica 08/2004; 124(1):11-7.
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    ABSTRACT: In CA1 neurons of guinea pig hippocampal slices, long-term depression (LTD) was induced in the field EPSP response in the absence of test synaptic inputs (one stimulus every 20 s) by application of the metabotropic glutamate receptor (mGluR) agonist, aminocyclopentane-1S, 3R-dicarboxylic acid (ACPD). This effect was blocked and long-term potentiation (LTP) was induced by co-application of N-methyl-D-aspartate (NMDA) during ACPD perfusion (ACPD/NMDA-induced LTD). These results indicate that the state of NMDA receptor activation during ACPD perfusion determines whether LTP or LTD is induced in hippocampal CA1 neurons. Co-application of an inositol 1, 4, 5-trisphosphate (IP3) receptor inhibitor, 2-aminotheoxydiphenyl borate, during ACPD application had no effect on the ACPD/NMDA-induced LTP, but increased the magnitude of the ACPD-induced LTD, suggesting that the ACPD/NMDA-induced LTP involves NMDA receptors, but not IP3 receptors, whereas the converse applies to the ACPD-induced LTD.
    Brain Research 03/2004; 999(1):20-8. · 2.88 Impact Factor
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    ABSTRACT: 1. Thyroid hormones play important roles in the development of the brain. Increasing evidence suggests that the deprivation of thyroid hormones in the early developmental stage causes structural and functional deficits in the CNS, but the precise mechanism underlying this remains elusive. In this study, we investigated the effects of thyroid hormones on synapse formation between cultured rat cortical neurons, using a system to estimate functional synapse formation in vitro. 2. Exposure to 10(-9) M thyroid hormones, 3,5,3'-triiodothyronine or thyroxine, caused an increase in the frequency of spontaneous synchronous oscillatory changes in intracellular calcium concentration, which correlated with the number of synapses formed. 3. The detection of synaptic vesicle-associated protein synapsin I by immunocytochemical and immunoblot analysis also confirmed that exposure to thyroxine facilitated synapse formation. 4. The presence of amiodarone, an inhibitor of 5'-deiodinase, or amitrole, a herbicide, inhibited the synapse formation in the presence of thyroxine. 5. In conclusion, we established a useful in vitro assay system for screening of miscellaneous chemicals that might interfere with synapse formation in the developing CNS by disrupting the thyroid system.
    Cellular and Molecular Neurobiology 01/2004; 23(6):895-906. · 2.29 Impact Factor
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    ABSTRACT: 1. Although microtubule-associated protein (MAP) 1B and its phosphorylation have been suggested to be important for synapse formation among cortical neurons, the localization of MAP1B in synapses has not yet been confirmed. In this report, we examine the localization of MAP1B in synaptic regions. 2. The localization of MAP1B was observed by immunohistochemical and electron microscopic techniques using specific antibodies against MAP1B. 3. MAP1B immunoreactivities were widely distributed in the cerebral cortex and were observed in the postsynaptic area but not in presynaptic terminals. 4. These synapses were classified as the asymmetrical type. 5. Only some synapses exhibited MAP1B immunoreactivities. MAP1B-immunopositive synapses accounted for about half of the total synapses. 6. Such a localization suggests MAP1B's important roles in synaptic functions.
    Cellular and Molecular Neurobiology 01/2004; 23(6):887-94. · 2.29 Impact Factor
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    ABSTRACT: Aluminum is environmentally abundant but not an essential trace element. Although there is increasing evidence suggesting the implication of aluminum in the pathogenesis of Alzheimer's disease, it is still controversial. We found and report here that aluminum maltolate, a stable and hydrophilic aluminum complex, causes death of primary cultured rat hippocampal neurons in a time- and dose-dependent manner. Degenerated neurons were TUNEL-positive. Immunohistochemical detection of synapsin I and microtubule associated protein 2 revealed the synapse loss between neurons intoxicated by aluminum maltolate. To explore the mechanism underlying its neurotoxicity, we administered various pharmacological compounds prior to the application of aluminum maltolate, and found that brain-derived neurotrophic factor (BDNF) markedly attenuated the neurotoxicity. Furthermore, aluminum maltolate inhibited the elevation of intracellular calcium levels caused by BDNF. Our results suggest the involvement of BDNF in the molecular mechanism underlying neurotoxicity induced by aluminum maltolate.
    Journal of Inorganic Biochemistry 10/2003; 97(1):124-31. · 3.20 Impact Factor
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    ABSTRACT: To investigate the roles of the GABAergic inhibitory system of accessory olfactory bulb (AOB) in pheromonal memory formation, we have developed a primary culture system of AOB neurons, which had numerous excitatory and inhibitory synapses. Using this culture system of AOB neurons, we examined the correlation in rats between neuronal excitation and synaptic morphology by bicuculline-induced disinhibition of cultured AOB neurons. The exposure to bicuculline induced long-lasting oscillatory changes in the intracellular calcium level ([Ca2+]in) of cultured non-GABAergic multipolar neurons, which were identified as mitral/tufted cells (MT cells). These MT cells exhibited the appearance of dendritic filopodia structures after a 10-min treatment with bicuculline. By labelling presynaptic terminals with FM4-64, the appearance of new presynaptic terminals was clearly observed on newly formed filopodia after 120 min treatment with bicuculline. These results suggest that bicuculline-induced [Ca2+]in oscillation of MT cells induces the growth of filopodia and subsequently the formation of new presynaptic terminals. Furthermore, tetrodotoxin or the deprivation of extracellular calcium blocked bicuculline-induced synapse formation. The present results indicate that the long-lasting [Ca2+]in oscillation caused by bicuculline-induced disinhibition of cultured MT cells is significantly implicated in the mechanism underlying synapse formation on cultured AOB neurons. Our established culture system of AOB neurons will aid in clarifying the mechanism of synapse formation between AOB neurons and the molecular mechanism of pheromonal memory formation.
    European Journal of Neuroscience 10/2003; 18(6):1343-52. · 3.75 Impact Factor
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    ABSTRACT: In CA1 neurons of guinea pig hippocampal slices, long-term potentiation (LTP) was induced by 10 min application of 10 microM aminocyclopentane-1S, 3R-dicarboxylic acid (ACPD), the metabotropic glutamate receptor (mGluR) agonist, in the presence of test synaptic inputs (once every 20 s). In contrast, long-term depression (LTD) was induced by application of 10 microM ACPD in the absence of test inputs. When 10 microM ACPD was applied in the presence of test inputs, co-application of the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate resulted in LTD induction when used at 50 microM. In ACPD-induced LTP, the delivery of test synaptic inputs to CA1 neurons could be replaced by co-application of NMDA (100 nM) during ACPD perfusion. These results suggest that, in CA1 neurons, a co-operative effect involving the activation of both mGluRs and NMDA receptors is required to trigger the process involved in ACPD-induced LTP. In addition, ACPD-induced LTD was blocked by co-application of an inositol 1,4,5-trisphosphate (IP3) receptor inhibitor, 2-aminotheoxydiphenyl borate (10 microM), which had no effect on ACPD-induced LTP. The results of the present study, therefore, indicate that ACPD-induced LTP involves NMDA receptors, but not IP3 receptors, whereas the converse applies to ACPD-induced LTD.
    Neuroscience Research 09/2003; 46(4):509-21. · 2.20 Impact Factor
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    ABSTRACT: Previously, we established a culture system of the accessory olfactory bulb in order to investigate the functional role of each accessory olfactory bulb neurons in pheromonal signal processing. In the present study, we developed a co-culture system of cultured accessory olfactory bulb neurons with partially dissociated cells of the vomeronasal organ. The dissociated cells of the vomeronasal organ form spherical structures surrounding a central cavity in culture, referred to as the vomeronasal pockets. The projection and activity of olfactory receptor neurons affect the differentiation and maturation of main olfactory bulb neurons. It was also reported induction of tyrosine hydroxylase expression in main olfactory bulb neurons when they were co-cultured with explants of the olfactory epithelium. Thus, we investigated the effects of co-culture with vomeronasal pockets on the differentiation and/or maturation of cultured accessory olfactory bulb neurons in relation to tyrosine hydroxylase expression. The number of tyrosine hydroxylase-containing neurons developmentally increased over time in the accessory olfactory bulb culture. This increase was significantly enhanced by coculture with vomeronasal pockets. Interestingly, a significant change in tyrosine hydroxylase expression was not observed when main olfactory bulb neurons were co-cultured with vomeronasal pockets. Moreover, significant changes in tyrosine hydroxylase expression were not observed when accessory olfactory bulb neurons were co-cultured with olfactory epithelium explants, as was previously observed in co-culture of main olfactory bulb neurons and olfactory epithelium explants. These results suggest that the differentiation and/or maturation of accessory olfactory bulb neurons is modified by vomeronasal organ neurons via specific interactions between the sensory organ and its target.
    Neuroscience 02/2003; 116(4):985-94. · 3.12 Impact Factor
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    ABSTRACT: Adenosine and ATP modulate cellular and tissue functions via specific P1 and P2 receptors, respectively. Although, in general, adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, little is known about the direct interaction between P1 and P2 receptors. We recently demonstrated that the G(i/o)-coupled adenosine A1 receptor (A1R) and G(q/11)-coupled P2Y1 receptor (P2Y1R) form a heteromeric complex with a unique pharmacology in cotransfected HEK293T cells using the coimmunoprecipitation of differentially epitope-tagged forms of the receptor [Yoshioka et al. (2001) Proc. Natl. Acad. Sci. USA 98, 7617-7622], although it remained to be determined whether this hetero-oligomerization occurs in vivo. In the present study, we first demonstrated a high degree of colocalization of A1R and P2Y1R by double immunofluorescence experiments with confocal laser microscopy in rat cortex, hippocampus and cerebellum in addition to primary cultures of cortical neurons. Then, a direct association of A1R with P2Y1R was shown in coimmunoprecipitation studies using membrane extracts from these regions of rat brain. Together, these results suggest the widespread colocalization of A1R and P2Y1R in rat brain, and both receptors can exist in the same neuron, and therefore associate as hetero-oligomeric complexes in the rat brain.
    FEBS Letters 12/2002; 531(2):299-303. · 3.58 Impact Factor
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    Satoshi Fujii, Hiroshi Kato, Yoichiro Kuroda
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    ABSTRACT: The effects of temperature on adenosine A1 receptor activation were studied both by electrophysiological analysis of synaptically evoked responses in CA1 neurons in guinea pig hippocampal slices, and by measuring the binding of adenosine analogues to adenosine A1 receptors in crude synaptosomes from guinea pig hippocampal neurons. Increasing the temperature of the perfusing medium from 30 degrees C to 45 degrees C attenuated the amplitude of the synaptically and the non-synaptically evoked CA1 population spikes. Bath application of 1 microM 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist, did not affect non-synaptically evoked CA1 population spikes, but significantly increased the amplitude of synaptically evoked population spikes in the upper range of hyperthermia (37-43 degrees C). In contrast, application of 5 microM L- N(6)-phenylisopropyladenosine, an adenosine A1 receptor agonist, did not affect non-synaptically evoked CA1 population spikes, but significantly decreased the amplitude of synaptically evoked population spikes in the upper range of hyperthermia. Binding assays using crude hippocampal synaptosomes showed that the affinity of adenosine A1 receptors for a radio-labeled adenosine analogue increased in response to a temperature increase. These results suggest that increased activation of adenosine A1 receptors in response to a temperature increase depresses excitatory synaptic responses in hippocampal CA1 neurons.
    Pflügers Archiv - European Journal of Physiology 04/2002; 443(5-6):713-9. · 4.87 Impact Factor
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    ABSTRACT: Zinc is an essential trace element and present at high concentrations in the central nervous system. Recent studies have revealed that excess amount of extracellular zinc is neurotoxic, and that the disruption of zinc homeostasis may be related to various neurodegenerative diseases. Zinc (25-100 microM) caused significant death of immortalized hypothalamic neuronal cells (GT1-7 cells) in a dose- and time-dependent manner. LD50 was estimated to be 34 microM. The degenerated cells were TUNEL-positive and exhibited apoptosis-like characteristics. Preadministration of sodium pyruvate (1-2 mM), a downstream energy substrate, inhibited the zinc-induced neurotoxicity in GT1-7 cells. GT1-7 cells can be used as a good tool for the investigation of zinc neurotoxicity in the hypothalamus.
    Cellular and Molecular Neurobiology 03/2002; 22(1):87-93. · 2.29 Impact Factor
  • S Fujii, H Kato, Y Kuroda
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    ABSTRACT: The mechanism of ATP-induced long-term potentiation (LTP) was studied pharmacologically using guinea-pig hippocampal slices. LTP, induced in CA1 neurons by 10 min application of 10 microM ATP, was blocked by co-application of the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (5 or 50 microM). In ATP-induced LTP, the delivery of test synaptic inputs (once every 20 s) to CA1 neurons could be replaced by co-application of NMDA (100 nM) during ATP perfusion. These results suggest that, in CA1 neurons, a co-operative effect between extracellular ATP and activation of NMDA receptors is required to trigger the process involved in ATP-induced LTP. In addition, ATP-induced LTP was blocked by co-application of an ecto-protein kinase inhibitor, K-252b (40 or 200 nM), whereas a P2X purinoceptor antagonist, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid 4-sodium (50 microM), or a P2Y purinoceptor antagonist, basilen blue (10 microM), had no effect.The results of the present study, therefore, indicate that the mechanisms of ATP-induced LTP involve the modulation of NMDA receptors/Ca(2+) channels and the phosphorylation of extracellular domains of synaptic membrane proteins, one of which could be the NMDA receptor/Ca(2+) channel.
    Neuroscience 02/2002; 113(3):617-28. · 3.12 Impact Factor
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    ABSTRACT: We examined the effects of temperature on excitatory synaptic transmission and the recurrent inhibitory loop in CA1 neurons in guinea pig hippocampal slices. Increasing the temperature of the perfusing medium from 30 to 49 degrees C resulted in attenuation of both the amplitude of the synaptically evoked CA1 population spikes and the paired-pulse inhibition (PPI) of the spikes. A bath application of 2 microM picrotoxin, a gamma-aminobutyric acid receptor antagonist, did not affect the amplitude of the CA1 population spikes, but it significantly reduced PPI during the early heating phase (30-32 degrees C). In contrast, the application of 1 mM theophylline or 50 microM 8-phenyltheophylline, a selective adenosine A1 receptor antagonist, resulted in significant augmentation of the PPI during the early phase of hyperthermia (30-34 degrees C) and a significant increase in the amplitude of the CA1 population spikes at higher temperatures (34-43 degrees C). These results suggest that increased activation of adenosine A1 receptors in response to a temperature increase depresses not only excitatory synaptic responses, but also the strength of the inhibitory circuit in CA1 neurons. Furthermore, hyperexcitability of CA1 pyramidal neurons was seen in the middle of the heating range (34-38 degrees C), excitatory responses still being present, but the strength of the inhibitory circuit significantly reduced.
    The Japanese Journal of Physiology 11/2001; 51(5):545-54. · 1.04 Impact Factor
  • M Kawahara, M Kato, Y Kuroda
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    ABSTRACT: Recent epidemiological, neuropathological, and biochemical studies have suggested a possible link between the neurotoxicity of aluminum and the pathogenesis of Alzheimer's disease. However, this relationship remains controversial. To investigate detailed characteristics of neurotoxicity of aluminum, we used primary cultured neurons of rat cerebral cortex as an in vitro model system for the observation of morphological changes induced by chronic exposure to aluminum. Although the exposure to aluminum chloride (10-100 microM) for 1 week did not cause marked neuronal death, degeneration of neuritic processes and accumulation of tau protein and beta-amyloid protein appeared after chronic exposure to 50 microM aluminum chloride for more than 3 weeks. We also investigated the polymerization of beta-amyloid protein in vitro using the immunoblotting technique. We thus found that aluminum induced conformational changes in beta-amyloid protein and enhanced its aggregation in vitro. The aggregated beta-amyloid protein was dissolved by the addition of desferrioxamine, a chelator of aluminum. The aggregated beta-amyloid protein pre-incubated with aluminum formed fibrillar deposits on the surface of cultured neurons.
    Brain Research Bulletin 06/2001; 55(2):211-7. · 2.94 Impact Factor
  • M Kawahara, Y Kuroda
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    ABSTRACT: 1. The elevation of intracellular Ca2+ levels ([Ca2+]i) in immortalized hypothalamic neurons (GT1-7 cells) after exposure to Alzheimer's beta-amyloid protein (AbetaP[25-35]) was investigated using a multisite fluorometry system. 2. The marked rise in [Ca2+]i appeared after exposure to 5-20-microM AbetaP[25-35]. Analysis of the spatiotemporal patterns of [Ca2+]i changes revealed that the magnitude and the latency of the response to AbetaP in each cell were highly heterogeneous. 3. The preadministration of 17beta-estradiol, 17alpha-estradiol, phloretin and cholesterol, which influence the properties of membranes, such as membrane fluidity or membrane potential, significantly decreased the rise in [Ca2+]i. 4. These findings support the idea that disruption of calcium homeostasis by AbetaP channels may be the molecular basis of the neurotoxicity of AbetaP and of the pathogenesis of Alzheimer's disease. It is also suggested that membrane properties may play key roles in the expression of neurotoxicity.
    Cellular and Molecular Neurobiology 03/2001; 21(1):1-13. · 2.29 Impact Factor
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    ABSTRACT: Previously, several studies attempting to analyze olfactory functions using dissociated culture systems of the olfactory bulb (OB) have been reported. Reciprocal dendrodendritic synapses between secondary neurons (mitral/tufted cells) and interneurons (periglomerular/granule cells) are considered to play the most important role in signal processing in the OB. However, it is unclear whether these reciprocal synapses are formed in vitro in the same way as they are in the intact OB. Thus, we synaptologically investigated the nature of cultured OB neurons. These neurons from embryonic rats were classified into four groups based on the size of their somata and their glutamic acid decarboxylase (GAD) immunoreactivity. At 14 days in vitro, most of the neurons synchronously showed spontaneous intracellular Ca2+ oscillations that were reversibly inhibited by application of D-APV and CNQX. Moreover, the frequency of the oscillations decreased and their amplitude became larger following application of bicuculline. These results suggest functional glutamatergic synaptic coupling and inhibitory GABAergic synaptic modulation. Immunocytochemical staining revealed many dot-like products (puncta) that were immunoreactive to GAD as well as to synaptophysin surrounding the cultured neurons. These results strongly indicate the presence of GABAergic synapses. The existence of synaptic contacts in OB neuron cultures was also confirmed by electron microscopy. Two types of synapses, symmetrical and asymmetrical, were morphologically recognizable. Moreover, we could also identify peculiar synapses resembling the in vivo reciprocal dendrodendritic synapses. The use of these primary culture systems will facilitate the elucidation of mechanisms underlying olfactory functions.
    Anatomy and Embryology 02/2001; 203(1):9-21. · 1.42 Impact Factor
  • Masahiro Kawahara, Yoichiro Kuroda
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    ABSTRACT: 1. The elevation of intracellular Ca2+ levels ([Ca2+]i) in immortalized hypothalamic neurons (GT1–7 cells) after exposure to Alzheimer's -amyloid protein (AP[25–35]) was investigated using a multisite fluorometry system.2. The marked rise in [Ca2+]i appeared afterexposure to 5–20-M AP[25–35]. Analysis of the spatiotemporal patterns of [Ca2+]i changes revealed that the magnitude and the latency of the response to AP in each cell werehighly heterogeneous.3. The preadministration of 17-estradiol, 17-estradiol, phloretin and cholesterol, which influence the properties of membranes, such as membrane fluidity or membrane potential, significantly decreased the rise in [Ca2+]i.4. These findings support the idea that disruption of calcium homeostasis by AP channels may be the molecular basis of the neurotoxicity of AP and of the pathogenesis of Alzheimer's disease. It is also suggested that membrane properties may play key roles in the expression of neurotoxicity.
    Cellular and Molecular Neurobiology 01/2001; 21(1):1-13. · 2.29 Impact Factor

Publication Stats

1k Citations
139.85 Total Impact Points

Institutions

  • 1991–2010
    • Tokyo Metropolitan Institute
      Edo, Tōkyō, Japan
  • 2005
    • Kochi Medical School
      Kôti, Kōchi, Japan
  • 2004
    • Nagoya University
      Nagoya, Aichi, Japan
    • Kyushu University of Health and Welfare
      Миядзаки, Miyazaki, Japan
  • 1997–2004
    • Yamagata University
      • Department of Physiology
      Ямагата, Yamagata, Japan
  • 1998
    • Tokyo Medical and Dental University
      • Department of Biochemical Genetics
      Edo, Tōkyō, Japan
  • 1993–1998
    • Nippon Telegraph and Telephone
      Edo, Tōkyō, Japan
  • 1990
    • Okayama University
      • Department of Chemistry
      Okayama, Okayama, Japan
  • 1986
    • Shinshu University
      • Department of Geology
      Shonai, Nagano, Japan