Nonperturbative study of the damping of giant resonances in hot nuclei.
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Biomedical subjects
Publications and source records attributed to M Tohyama.
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The spinal cord potentials (SCPs) were recorded from the dorsal root entry zone (DREZ) and posterior epidural space in patients before and after dorsal root entry zone lesion (DREZL) during general anaesthesia. The SCPs from the DREZ activated by segmental, ascending and descending volleys were basically the same in fundamental waveform as those recorded from the posterior epidural space. Segmentally activated slow negative (N1) wave, reflecting synchronized activities of dorsal horn neurones, and positive (P2) wave, thought to indicate primary afferent depolarization, were affected by DREZL in all 4 subjects tested, even by contralateral stimulation, suggesting that these components of the segmental SCPs in man partly reflect the activities of the contralateral dorsal horn. The spike-like potentials activated by ascending volleys were not affected by DREZL, while the subsequent slow components were decreased in the lesioned level. This may indicate that ascending spinal cord tracts are not affected by the operation, and suggests that the origin of the slow components by ascending volleys lies at least in part in the segmental dorsal horn. The slow negative and positive components, recorded at a remote segment from DREZL, in response to the descending volleys, were augmented after DREZL, suggesting that activation of ascending or descending inhibition through a feedback loop via the supraspinal structures might occur at least transiently following DREZL. All components of the SCPs activated by descending volleys were decreased or disappeared in recording from the lesioned level, as expected. Thus, intra-operative recording of the SCPs during DREZL might be beneficial for monitoring and studying human spinal cord function.
We examined the ontogenesis of a subtype of metabotropic glutamate receptors, termed mGluR1, which is linked to phosphoinositide metabolism, in various regions of rat brain during neonatal development. Northern blot analyses of mGluR1 mRNA indicated that mRNA increased monotonously or remained at plateau levels during the first 5 weeks after birth. In situ hybridization analyses supported this conclusion. The result is in contrast with the reported development of the activity in excitatory amino acid-stimulated phosphoinositide turnover during the same period. The latter increases during the first few weeks and then decreases sharply.
The expression of mRNAs encoding the alpha 3 and alpha 4 subunits of the gamma-aminobutyric acid A (GABAA) receptor in the rat brain was investigated by in situ hybridization histochemistry. Both subunits showed a wide but uneven distribution, which did not coincide with the distribution of any other subunit so far reported. The cerebral cortex, anterior olfactory nucleus, lateral septum, subiculum, lateral and medial nuclei of the amygdaloid complex, anterior nuclei of the thalamus, pars compacta of the substantia nigra, trigeminal sensory nuclei, and cochlear nucleus were some of the areas where strong expression of mRNA for both the alpha 3 and alpha 4 subunits was detected. In the mitral cell layer of the olfactory bulb, the preoptic area and locus coeruleus, strong expression of only the alpha 3 subunit was detected. In the granular cell layer of the olfactory bulb, caudate-putamen, tenia tecta, pyramidal cell layer of the CA region and granular cell layer of the dentate gyrus in the hippocampal formation, dorsomedial and ventrolateral nuclei of the thalamus, dorsal part of the lateral geniculate body, preolivary nuclei and pontine nuclei, only the alpha 4 subunit showed strong expression. The diverse distribution of these two subunits is considered to indicate that each has a different role in the central nervous system.
We examined the expression of the beta subunit mRNA of the glycine receptor and the gamma subunit mRNA of the GABAA receptor in the rat dorsal root ganglion (DRG) using in situ hybridization histochemistry with oligonucleotide probes. About 44% and 37% of the all DRG neurons were labeled by the probes for glycine receptor beta subunit and GABAA receptor gamma subunit mRNAs. Labeled neurons were mostly large cells that simultaneously expressed both glycine receptor beta subunit and GABAA receptor gamma subunit mRNA as demonstrated using consecutive sections. Thus, we suggest the possibility that both GABA and glycine presynaptically regulate the activity of neurons involved in low-threshold mechanoreception at axo-axonic synapses in the spinal cord.
Localization of mRNA for the c-kit receptor and its ligand (Sl factor) in the brain of adult rats was studied using in situ hybridization histochemistry. The mRNA for the c-kit receptor was detected in the forebrain, the lower brain stem and the cerebellum. In the forebrain, the c-kit mRNA signals were detected in the olfactory bulb, the caudate-putamen, throughout the superficial cortex, the accumbens nucleus, the nucleus of vertical limb diagonal band, the bed nucleus of anterior commissure, Ammon's horn, the entopeduncular nucleus, the subthalamic nucleus, the dorsal raphe nucleus, the parasubiculum, the presubiculum, the ventricular nucleus of lateral lemniscus, and the entorhinal cortex. In the lower brain stem, the signals were detected in the inferior colliculus, the spinal vestibular nucleus, the spinal tract nucleus of trigeminal nerve, and the pyramidal tract. In the cerebellum, the signals were detected in the molecular layer of the cortex and cerebellar nuclei. By contrast, the signals of mRNA for Sl factor were detected in the forebrain and the cerebellum. In the forebrain, the signals were detected in the olfactory bulb, the endopiriform nucleus, the septohippocampal nucleus, the habenular nuclei, and most of the thalamic nuclei. In the cerebellum, the signals were detected in Purkinje cells. Several pairs of structures were found in which mRNA of either the c-kit receptor or the Sl factor was expressed and between which the synaptic connection had been reported, suggesting that the interaction between the c-kit receptor and the Sl factor may play some roles in the development of such synaptic connections.
The distribution of GABAA receptor gamma 1 subunit was examined in the rat central nervous system using in situ hybridization histochemistry. The gamma 1 subunit was expressed in relatively limited areas compared to other subunits investigated previously. The brain regions strongly expressing this subunit were the septum, globus pallidus, bed nucleus of the stria terminalis, hypothalamic periventricular nucleus, supraoptic nucleus, medial and central nuclei of the amygdaloid complex, medial part of the medial geniculate body, substantia nigra pars reticulata, interpeduncular nucleus, lateral parabrachial nucleus, Purkinje cell layer of the cerebellum, and inferior olivary nucleus. This relatively limited expression implies a possible role of gamma 1 subunit in relation to some specific neuronal circuit.
Co-localization of the alpha 1 and beta 2 subunit mRNAs of the GABAA receptor was examined on serial sections of the rat magnocellular preoptic nucleus using in situ hybridization histochemistry. More than half of the labeled neurons in this nucleus contained both transcripts, while 31.9% and 17.4% of them contained only alpha 1 or beta 2 subunit mRNA, respectively. These results indicate that there may be three GABAA receptor subtypes in this nucleus, with co-localization of the alpha 1 and beta 2 subunits occurring in the most common subtype.
The expression of GABAA receptor alpha 1 subunit mRNA in the postnatal rat forebrain was examined by in situ hybridization histochemistry. In most regions, including the isocortex, olfactory bulb, amygdala, septum, nucleus of the diagonal band, bed nucleus of the stria terminalis, basal ganglia, thalamus, and hypothalamus, the expression of alpha 1 subunit mRNA was low at birth but showed a dramatic increase during the early postnatal period. Adult levels of expression were reached at around the second or third week of life in these regions. However, in the caudate-putamen, and the nucleus accumbens, the expression of this subunit was only transient.
The Src-like protein-tyrosine kinases Fyn and Lyn are expressed in lymphocytes. Fyn is expressed in T cells at elevated levels and is associated with the T cell antigen receptor complex, whereas Lyn is expressed in B cells and is associated with membrane-bound immunoglobulin. Thus, these kinases are suggested to participate in antigen-mediated signal transduction in lymphocytes. Previous report showed that fyn was also expressed in brain, but its cellular distribution was not examined. Expression of Lyn in neural tissues was not previously reported. Here we report that both fyn and lyn are expressed in discrete regions of the brain. To throw light on their functions in the brain, we investigated their expressions during brain ontogenesis in mice. In situ hybridization analysis showed that Fyn mRNA was specifically expressed in neurons of embryos and newborn mice. In adult animals, fyn mRNA was expressed in oligodendrocytes as well as neurons. In contrast, the expression of lyn mRNA was relatively low in brains of embryos and newborn mice, but in adults the transcript was specifically expressed in the granular layer of the cerebellum. Therefore, the Fyn and Lyn kinases may regulate distinct functions of specific cells during brain development. The specific expressions of Fyn and Lyn in both lymphatic and neural tissues could suggest common signalling mechanisms in the immune system and central nervous system.
The localization of neurons containing mRNA of the gamma 2-subunit of GABAA receptors was examined in the rat central nervous system with in situ hybridization histochemistry using an oligonucleotide probe to the sequence of the gamma 2-subunit. Neurons containing the gamma 2-subunit mRNA were widely but unevenly distributed in the brain. The location of gamma 2-subunit mRNA-containing neurons differed from those containing alpha- or beta-subunits. According to our results brain regions can be divided into three categories: one containing only gamma 2-subunit, one containing mRNA of at least one subunit other than gamma 2 and one containing more than one other subunit but not the gamma 2-subunit. The distribution of strongly labeled nuclei partly coincided with that of glutamate decarboxylase, suggesting that the GABAA receptor gamma 2-subunit would be involved in an autoreceptive mechanism of the GABAergic transmission.
Developmental changes of the expression of various GABAA receptor subunits (alpha 1, alpha 3, alpha 4, beta 1-3, and gamma 2) were examined in the fetal rat cerebral cortex using in situ hybridization histochemistry. The subunits showed three main patterns of development. The alpha 1 subunit showed the first pattern, in which no expression was observed during embryonic development. The alpha 4 and beta 1 subunits showed the second pattern, in which expression was observed in both the undifferentiated neuroepithelium and the developing cortical layers. The alpha 3, beta 2, beta 3, and gamma 2 subunits showed the third pattern, in which expression was only seen in the developing cortical layers. These findings strongly suggest the following: (i) the alpha 1 subunit is involved in GABAergic transmission in the mature cerebral cortex; (ii) the alpha 4 and beta 1 subunits are involved in both the differentiation of the neuroepithelium and the development of the cortical plate, and (iii) the alpha 3, beta 2, beta 3, and gamma 2 subunits are involved in the development of the cortical plate. Subunits already expressed on embryonic day 13 (beta 1, beta 3, and gamma 2) appear especially likely to have a special role in neuronal development.
In situ hybridization histochemistry revealed three different ontogenetic patterns of localized expression of the high-affinity type of neurotensin receptor mRNA in the developing rat brain: one comprises sites which showed transient expression of neurotensin receptor mRNA during the first postnatal week, the expression greatly decreasing thereafter (type I); another comprises sites at which there is a gradual increase in neurotensin receptor mRNA after birth, as there is in cell number and intensity, with advancing age, followed by a plateau (type II); the third comprises sites at which there is much expression of neurotensin receptor mRNA already at birth, and a slight decrease thereafter (type III). The cerebral cortex, except retrosplenial and entorhinal cortices, and the anterior dorsal thalamic nucleus exhibit the type I pattern, while the horizontal and vertical limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata, ventral part of the suprachiasmatic nucleus, medial habenular nucleus, ventral tegmental area and substantia nigra pars compacta exhibit the type II pattern. The tenia tecta, retrosplenial and entorhinal cortices exhibit the type III pattern. One of the most striking findings in this study was that the entire neocortex and most of the limbic cortex exhibit the type I pattern, i.e. neurotensin receptor mRNA is expressed transiently long before a neuronal network is established there. This suggests that neurotensin plays an important role in cortical development, other than its reported transmitter-like role in the adult.
Immunocytochemical double-staining analysis revealed that in the rat anterior pituitary 86% of cells containing the beta II-subspecies of protein kinase C also contained follicle stimulating hormone (FSH), and that 22% of these FSH cells expressed the beta II-subspecies. These findings suggest a close relationship between the beta II-subspecies of protein kinase C and FSH regulation.
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The present study examined substance P (SP) innervation in the suprachiasmatic nucleus (SCN) of the rat. In the colchicine-untreated rat, SP-immunoreactive fibers formed a dense oval plexus in the ventral part of the SCN. After bilateral eye enucleation, there was a marked reduction in SP-immunoreactive fibers in the ventral part of the SCNs. The SP-immunoreactive neurons in the retinal ganglion cell layer were retrogradely labeled after injection of Fluoro-gold into the SCN. These findings indicate the presence of the SP innervation from the retina to the SCN in the rat. The role of SP in the retino-hypothalamic tract was discussed from the light-dark cycle.
The localization of the glycine cleavage system was examined in the rat brain by immunohistochemistry using an antibody to P-protein (a constituent of the system). In all sites studied, the enzyme was confined to the astrocytes. The intensity of astrocyte staining varied in different brain regions, with the strongest staining being noted in the hippocampus, the cerebellar cortex, the Bergmann glia in the cerebellum and the Muller cells in the retina. The weakest staining was seen in the brainstem and spinal cord. P-protein was found to be located in the mitochondria by an ultrastructual study.