Search PubMed⌕ Search

Biomedical subjects

N Mizuno

Publications and source records attributed to N Mizuno.

At least 163 records · Page 9Linked to original sources

Direct projections from the deep layers of the superior colliculus to the subthalamic nucleus in the rat.

Direct projections from the superior colliculus to the subthalamic nucleus were found in the rat in antero- and retrograde tracing experiments; these projections arose mainly from the deep layers of the superior colliculus at its middle to caudal levels. The present findings suggest that signals from the deep layers of the superior colliculus may modulate the basal ganglia activity during orienting behavior.

Animals↗

Direct projections from the non-laminated divisions of the medial geniculate nucleus to the temporal polar cortex and amygdala in the cat.

The medial geniculate nucleus (MG) is well known to send projection fibers not only to the auditory cortex, but also to the limbic structures of the forebrain including the perirhinal cortex and amygdala. In the cat, the non-laminated portions of the MG are also known to project to the amygdala, as well as to the auditory cortical areas surrounding the primary auditory area. On the other hand, projections from the non-laminated MG to the limbic cortical areas have not so far been studied systematically. Thus, in the present study, direct projections from the non-laminated portions of the medial geniculate nucleus to the temporal polar cortex and amygdala were examined in the cat by retrograde and anterograde tract-tracing techniques. The temporal polar cortex is the ventral polar region of the posterior sylvian and posterior ectosylvian gyri, which is located dorsal to the posterior rhinal sulcus and includes the ectorhinal area. After injection of cholera toxin B subunit into the temporal polar cortex, retrogradely labeled neurons were seen in the caudal two-thirds of the medial geniculate nucleus ipsilateral to the injection; they were distributed in the non-laminated portions of the MG (the dorsal and medial divisions and the ventromedial part of the ventral division), but not in the laminated portion (the principal part of the ventral division). These findings were confirmed by injecting Phaseolus vulgaris leucoagglutinin into each division of the MG. After the injection into each non-laminated division, terminal labeling was observed in the temporal polar cortex. Terminal labeling was further found in the lateral amygdaloid nucleus ipsilateral to the injection. Then, cholera toxin B subunit was injected into the lateral amygdaloid nucleus; retrogradely labeled neurons were observed ipsilaterally in the non-laminated portions of the MG, as well as in the temporal polar cortex. The results indicate that the non-laminated portions of the MG send projection fibers to the temporal polar cortex and lateral amygdaloid nucleus, and that the non-laminated portions of the MG and temporal polar cortex give rise to overlapping projections to the lateral amygdaloid nucleus. These connections appear to constitute neuronal links in "emotional" and/or "motivational" circuitry in the forebrain.

Amygdala↗

Immunohistochemical localization of substance P receptor in the superior colliculus. A light and electron microscope study in the rat.

The superficial layers of the superior colliculus (SC) have been known to contain many axons showing substance P-like immunoreactivity (SP-LI). We, therefore, immunohistochemically examined the distribution of SP receptor (SPR) in the superficial layers of the SC in the rat by using a specific antibody against SPR. The majority of SC neurons with SPR-LI were distributed in the zonal and the superficial gray layers, the rest of them were in the optic layer. Electron microscopy revealed that SPR-immunoreaction products in SC neurons were distributed not only in postsynaptic sites, but also in non-synaptic regions of perikaryal and dendritic profiles.

Animals↗

Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction.

A cDNA clone for a new rat metabotropic glutamate receptor termed mGluR7 was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic receptor (mGluR) family and by the subsequent screening of a rat forebrain cDNA library. The cloned mGluR7 subtype consists of 915 amino acid residues and exhibits a structural architecture common to the mGluR family with a large extracellular domain preceding the seven putative membrane-spanning domains. mGluR7 shows the highest sequence similarity to mGluR4 and mGluR6 among the members of the mGluR family. Similar to mGluR4 and mGluR6, mGluR7 inhibits forskolin-stimulated cyclic AMP accumulation in response to agonist interaction and potently reacts with L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate in Chinese hamster ovary cells transfected with the cloned cDNA. RNA blot and in situ hybridization analyses of mGluR7 mRNA indicated that it is widely expressed in many neuronal cells of the central nervous system and is thus different from the more limitedly expressed mGluR4 or mGluR6 mRNA. mGluR7 together with mGluR4 thus corresponds to the putative L-2-amino-4-phosphonobutyrate receptor which plays an important role in modulation of glutamate transmission in the central nervous system.

Amino Acid Sequence↗

Immunocytochemical localization of antigens in adult worms of Trichinella spiralis recognized by Fischer rats.

We demonstrate the tissue localization, in adult Trichinella spiralis, of antigens recognized by Fischer rat sera at 32 weeks postinfection. Immunodominant antigens were located in a wide variety of tissues, including type 1 stichocyte granules, stichocyte cytoplasm, the canalicular tree, hemolymph, hypodermis, hypodermal glands, cord cytoplasm, intestinal-gland cell granules, membranous structures in the midgut epithelium, midgut-occupying substance, brush border, hindgut epithelial cytoplasm, hindgut cuticle, vaginal cuticle, epithelial cytoplasm of the female genital tract, microvilli and discrete areas of the ovum, embryo sheath, intersperm space, discrete areas in immature sperm, small granules and cup-shaped membrane structures of sperm, and exocrine granules in the seminal vesicle and ejaculatory duct. A small amount of antigen was located in the inner layers of the genital portion of the body cuticle. The precise localization of antigens in adult worms should form a basis for better analysis of T. spiralis-related immunology.

Animals↗

Topographic organization of collateral projections from the basolateral amygdaloid nucleus to both the prefrontal cortex and nucleus accumbens in the rat.

The basolateral amygdaloid nucleus, a limbic/autonomic center in the basal forebrain, has been known to send projection fibers to the prelimbic and dorsal agranular insular areas in the prefrontal cortex, as well as to the nucleus accumbens. In the present study, we investigated single basolateral amygdaloid nucleus neurons sending their axons to both the prefrontal cortex and nucleus accumbens. The fluorescent retrograde double-labeling technique was employed in the rat; True Blue was injected into the prelimbic or dorsal agranular insular cortex, and Diamidino Yellow into the medial or lateral part of the nucleus accumbens. The majority of basolateral amygdaloid nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic cortex were located, respectively, in the rostral two-thirds or caudal two-thirds of the nucleus, while those projecting to the medial or lateral part of the nucleus accumbens were diffusely distributed in the nucleus. Almost 50% of basolateral amygdaloid nucleus neurons projecting to the prelimbic cortex sent their axon collaterals to the medial part of the nucleus accumbens. About 30-40% of basolateral amygdaloid nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic cortex issued their axon collaterals to the lateral part of the nucleus accumbens. The axons bifurcating to both the dorsal agranular insular cortex and lateral part of the nucleus accumbens, those bifurcating to both the prelimbic cortex and lateral part of the nucleus accumbens, or those bifurcating to both the prelimbic cortex and medial part of the nucleus accumbens arose preferentially from the rostral, middle or caudal parts of the basolateral amygdaloid nucleus, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

Morphological and chemical characteristics of substance P receptor-immunoreactive neurons in the rat neocortex.

Substance P receptor-expressing neurons in the rat cerebral neocortex were examined by single- and double-immunolabeling methods with an affinity-purified specific antibody to substance P receptor. Substance P receptor immunoreactivity was observed exclusively in non-pyramidal neurons. About a quarter of these substance P receptor-positive neocortical neurons showed intense immunoreactivity, and the other three quarters displayed weak substance P receptor immunoreactivity. The neurons showing intense substance P receptor immunoreactivity were large multipolar cells with a few long aspiny or sparsely-spiny dendrites, and were scattered throughout the neocortical layers except for layer I, and also in the underlying white matter. The weakly immunoreactive neurons were medium-sized multipolar cells with oval to round somata and aspiny varicose dendrites, and were distributed in all cortical layers with a bias to layers II-III and the superficial part of layer V. The double-immunofluorescence study revealed that almost all substance P receptor-positive neurons were immunoreactive for GABA, but negative for glutaminase. Substance P receptor immunoreactivity in GABAergic neocortical neurons were further examined by the double-immunofluorescence method with antibodies to markers for subgroups of GABAergic neurons. Somatostatin immunoreactivity was found in 89% of neurons with intense substance P receptor immunoreactivity, and in 1.5% of neurons with weak substance P receptor immunoreactivity. Neuropeptide Y immunoreactivity was also observed in 92% of neurons with intense immunoreactivity for substance P receptor, and in 1.6% of neurons with weak immunoreactivity for substance P receptor. In contrast, parvalbumin immunoreactivity was seen in 1.3% of neurons with intense substance P receptor immunoreactivity, and in 59% of weak substance P receptor immunoreactivity. Calbindin D28k immunoreactivity was found in 12 and 19% of neurons, respectively, with weak and intense immunoreactivities for substance P receptor. Virtually no cells showing substance P receptor immunoreactivity displayed immunoreactivity for vasoactive intestinal polypeptide or choline acetyltransferase. These results indicate that the neocortical neurons expressing substance P receptor constitute a subpopulation of GABAergic non-pyramidal cells, and are segregated into neurons with intense immunoreactivity and those with weak immunoreactivity for substance P receptor; the vast majority of neurons with intense substance P receptor immunoreactivity contain somatostatin and neuropeptide Y, and the majority of neurons with weak substance P receptor immunoreactivity have parvalbumin.

Animals↗

Glutamate-synthesizing enzymes in GABAergic neurons of the neocortex: a double immunofluorescence study in the rat.

L-Glutamate is the immediate precursor of the inhibitory transmitter GABA, and considered to be supplied from alpha-ketoglutarate through a transamination reaction or from glutamine through a glutaminase reaction. In the present study, the localization of aspartate aminotransferase and glutaminase in GABAergic neurons was investigated in the rat neocortex by a double immunofluorescence method. Immunoreactivities for both soluble and mitochondrial aspartate aminotransferases were detected in more than 90% of GABA-positive neurons, whereas glutaminase immunoreactivity was not found in GABA-positive neurons. All neocortical neurons with soluble aspartate aminotransferase immunoreactivity were immunopositive for GABA, but none for glutaminase. Neurons with mitochondrial aspartate aminotransferase immunoreactivity showed either glutaminase or GABA immunoreactivity. Under confocal laser scan microscopy, immunoreactivity for soluble aspartate aminotransferase was observed in many axons and axon terminals showing immunoreactivity for glutamic acid decarboxylase, whereas immunoreactivity for mitochondrial aspartate aminotransferase was seen in only a few axons displaying immunoreactivity for glutamic acid decarboxylase. The present results indicate that soluble aspartate aminotransferase is selectively localized to cell bodies and axon terminals of GABAergic non-pyramidal neurons in the cerebral neocortex. This suggests that glutamate is supplied from alpha-ketoglutarate via transamination and works as the immediate precursor for GABA in axon terminals of GABAergic neurons. The absence of glutaminase immunoreactivity in GABAergic neurons indicates that glutamine is a "metabolically remote" precursor for GABA. Mitochondrial aspartate aminotransferase was located in perikarya, rather than in axon terminals of GABAergic neurons, suggesting a transmitter-irrelevant role of this enzyme in neurons.

Animals↗

Single neurons in the ventral tegmental area that project to both the cerebral and cerebellar cortical areas by way of axon collaterals.

Recently, we have found that the ventral tegmental area of the rat sends dopaminergic and non-dopaminergic axons, respectively, to the cerebellar cortex and deep cerebellar nuclei [Ikai et al. (1992) Neuroscience 51, 719-728]. In the present study, employing fluorescent retrograde double labeling with Fast Blue and Diamidino Yellow, we examined whether individual neurons in the ventral tegmental area of the rat send their axons to both the cerebellum and other brain regions. The neurons projecting to the cerebellar cortex often issued axon collaterals to the cerebral cortical areas, including the prelimbic-anterior cingulate cortices and piriform-entorhinal cortices, but not so frequently to the subcortical regions, including the nucleus accumbens, lateral septum, amygdala, and lateral habenula. On the other hand, the neurons projecting to the deep cerebellar nuclei rarely sent axon collaterals to the cerebral cortical and subcortical regions.

Animals↗

Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 in the mouse nervous system.

Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 was investigated by in situ hybridization in the nervous system of the mouse. The hybridization signals for EP3 were widely distributed in the brain and sensory ganglia and specifically localized to neurons. In the dorsal root and trigeminal ganglia, about half of the neurons were labeled intensely. In the brain, intensely labeled neurons were found in Ammon's horn, the preoptic nuclei, lateral hypothalamic area, dorsomedial hypothalamic nucleus, lateral mammillary nucleus, entopeduncular nucleus, substantia nigra pars compacta, locus coeruleus and raphe nuclei. Moderately labeled neurons were seen in the mitral cell layer of the main olfactory bulb, layer V of the entorhinal and parasubicular cortices, layers V and VI of the cerebral neocortex, nuclei of the diagonal band, magnocellular preoptic nucleus, globus pallidus and lateral parabrachial nucleus. In the thalamus, moderately labeled neurons were distributed in the anterior, ventromedial, laterodorsal, paraventricular and central medial nuclei. Based on these distributions, we suggest that EP3 not only mediates prostaglandin E2 signals evoked by blood-borne cytokines in the areas poor in the blood-brain barrier, but also responds to those formed intrinsically within the brain to modulate various neuronal activities. Possible EP3 actions are discussed in relation to the reported neuronal activities of prostaglandin E2 in the brain.

Animals↗

Topographical organization of subicular neurons projecting to subcortical regions.

Direct projections from the subiculum to the septum, thalamus, and hypothalamus were studied in the rat by the fluorescent retrograde double-labeling technique with Fast blue and Diamidino yellow. The results confirm and extend the previously reported findings. The dorsal subiculum projects primarily to the lateral septum, anterior and midline thalamus, and mammillary complex. The distribution areas of cell bodies of these projection neurons are substantially segregated, depending on their target region, and few single neurons project to two of the target regions by way of axon collaterals. The ventral subiculum projects mainly to the lateral septum, midline thalamus, and ventromedial hypothalamic area. The distribution areas of cell bodies of these projection neurons are considerably overlapped with one another, and a number of single neurons send axon collaterals to two of the lateral septum, midline thalamus, and ventromedial hypothalamic area. It is, thus, indicated that the populations of subicular neurons projecting to each of the subcortical structures examined are more distinctly segregated in the dorsal subiculum than in the ventral subiculum.

Amidines↗

Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex.

The distribution of the metabotropic glutamate receptors mGluR2 and mGluR3 was immunohistochemically examined in the rat cerebellar cortex at both light and electron microscope levels. An antibody was raised against a fusion protein containing a C-terminal portion of mGluR2. On immunoblot, the antibody reacted with both mGluR2 and mGluR3 in rat brain. mGluR2/3 immunoreactivity was expressed in cell bodies, dendrites, and axon terminals of Golgi cells, as well as in presumed glial processes. Golgi axon terminals with mGluR2/3 immunoreactivity were often encountered in the vicinity of glutamatergic mossy fiber terminals. The results suggest that transmitter glutamate may exert control influences upon Golgi cells not only through dendritic mGluR2/3, but also through axonal mGluR2/3.

Animals↗

Substance P receptor-immunoreactive neurons in the rat neostriatum are segregated into somatostatinergic and cholinergic aspiny neurons.

Immunochemical characteristics of neostriatal neurons producing substance P receptor (SPR) were examined in adult rats by double- and triple-immunofluorescence methods. In the neostriatum, SPR immunoreactivity was detected in large and medium-sized aspiny neurons. Virtually all SPR-immunoreactive neurons in the neostriatum contained somatostatin (SS) or choline acetyltransferase (ChAT), but not parvalbumin. All SS- and ChAT-immunoreactive neurons in the neostriatum showed SPR immunoreactivity. The co-existence of SS and ChAT was, however, not found in single neurons expressing SPR immunoreactivity. The present results indicate that neostriatal neurons immunoreactive for SPR are segregated into 2 groups: (1) medium-sized, spiny somatostatinergic, and (2) large, aspiny cholinergic neurons.

Animals↗

Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb.

Various functions of glutamate transmission are mediated by both ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGluRs) consists of at least six different subtypes that are classified into three subgroups, mGluR1/mGluR5, mGluR2/mGluR3, and mGluR4/mGluR6 (refs 1-5), but their physiological roles are largely unknown. Here we report the identification of a very potent agonist for mGluR2/mGluR3, DCG-IV, and the specific localization of mGluR2 in granule cell dendrites that form dendrodendritic synapses with mitral cells in the accessory olfactory bulb. Using the DCG-IV agonist for mGluR2 in combination with slice patch-recording, we demonstrate that the granule cell mGluR2 presynaptically suppresses inhibitory GABA (gamma-aminobutyrate) transmission to the mitral cell. Our results indicate that mGluR2 in granule cells plays an important role in the persistent excitation of olfactory sensory transmission in the accessory olfactory bulb by relieving mitral cells from the GABA inhibition.

Animals↗

Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain.

A trpE-fusion protein containing a C-terminal sequence of a rat metabotropic glutamate receptor, mGluR5, was used to produce an antibody. On immunoblot, the antibody specifically reacted with mGluR5 expressed in mammalian cells and rat brain. Immunohistochemical analysis revealed intense mGluR5-like immunoreactivity (LI) in the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, cerebral cortex, hippocampus, lateral septum, striatum, nucleus accumbens, inferior colliculus, and spinal trigeminal nuclei. The distribution pattern of mGluR5-LI corresponds very well with that of mGluR5 mRNA. Electron microscope analysis of the striatum revealed dense accumulation of immunoreaction products in dendrites which were often provided with asymmetrical synapses. These results suggest that mGluR5 is predominantly located in postsynaptic elements.

Animals↗

Induction of cholinergic and adrenergic differentiation in N-18 cells by differentiation agents and DNA demethylating agents.

Effects of various differentiating agents and DNA demethylating agents on the expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), marker enzymes for cholinergic and adrenergic differentiation, respectively, were examined in N-18 neuroblastoma cells. Retinoic acid (RA) and a medium conditioned over C6-glioma cells (GCM), which have been shown to enhance the ChAT activity of PC12 cells, NG108-15 cells and fetal rat brain cells, did not induce ChAT activity of N-18 cells. Treatment of the cells with the DNA demethylating agents alone also did not affect ChAT activity. But after pretreatment of the cells with the DNA demethylating agents, ChAT activity of N-18 cells was greatly increased by either RA or GCM. TH activity of N-18 cells was enhanced by forskolin, an activator of adenylate cyclase. The pretreatment of the cells with the DNA demethylating agents greatly enhanced the induction of TH activity by forskolin. Levels of ChAT and TH messenger RNA were altered in accordance with changes in ChAT and TH activities. Possible mechanisms of the actions of the demethylating agents on cholinergic and adrenergic differentiation are discussed.

Acetylcholine↗

Identification of periaqueductal gray and dorsal raphe nucleus neurons projecting to both the trigeminal sensory complex and forebrain structures: a fluorescent retrograde double-labeling study in the rat.

The midbrain periaqueductal gray (PAG) including the dorsal raphe nucleus (DR) has been known to contain serotoninergic neurons projecting to many brain regions. Employing fluorescent retrograde double labeling combined with immunofluorescence histochemistry for serotonin (5-HT), we examined in the rat whether or not single PAG/DR neurons with 5-HT send their axons to both the trigeminal sensory complex and forebrain regions. Stereotaxic injections of Diamidino Yellow (DY) and Fast Blue (FB) were performed unilaterally; DY was injected into the caudal spinal trigeminal nucleus or principal sensory trigeminal nucleus, and FB into the ventrolateral orbital cortex, nucleus accumbens or amygdala. A small percentage of PAG/DR neurons were doubly labeled with DY and FB, and the majority of them showed 5-HT-like immunoreactivity (5-HT-LI). Most of these 5-HT-LI PAG/DR neurons that were indicated to send their axons simultaneously to both the trigeminal sensory complex and forebrain regions were distributed in the ventrolateral PAG subdivision and ventral aspects of the medial PAG subdivision at the middle and caudal PAG levels, bilaterally with a predominant distribution on the side ipsilateral to the injections. This indicates a possible role of these PAG/DR neurons in the limbic or affective-motivational aspect of the pain-related neural system.

Amidines↗

Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain.

Glutathione-independent prostaglandin D synthase [prostaglandin-H2 D-isomerase; (5Z,13E)-(15S)-9 alpha,11 alpha-epidioxy-15-hydroxyprosta-5,13-dienoate D-isomerase, EC 5.3.99.2] is an enzyme responsible for biosynthesis of prostaglandin D2 in the central nervous system. In situ hybridization with antisense RNA for the enzyme indicated that mRNA for the enzyme was predominantly expressed in the leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain. The findings agree with those obtained by immunohistochemical staining with antibodies against the enzyme. It was further revealed that prostaglandin D synthase activity was considerably greater in the isolated leptomeninges (14.2 nmol per min per mg of protein) and choroid plexus (7.0 nmol per min per mg of protein) than the activity in the whole brain (2.0 nmol per min per mg of protein). These results, taken together, indicate that the enzyme is mainly synthesized and located in the leptomeninges, choroid plexus, and oligodendrocytes in the brain.

Animals↗