bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silicon chip with capacitors and transistors for interfacing organotypic brain slice of rat hippocampus
Authors: Hutzler Michael , Fromherz Peter 
Published: April 2004

AbstractProbing projections between brain areas and their modulation by synaptic potentiation requires dense arrays of contacts for noninvasive electrical stimulation and recording. Semiconductor technology is able to provide planar arrays with high spatial resolution to be used with planar neuronal structures such as organotypic brain slices. To address basic methodical issues we developed a silicon chip with simple arrays of insulated capacitors and field‐effect transistors for stimulation of neuronal activity and recording of evoked field potentials. Brain slices from rat hippocampus were cultured on that substrate. We achieved local stimulation of the CA3 region by applying defined voltage pulses to the chip capacitors. Recording of resulting local field potentials in the CA1 region was accomplished with transistors. The relationship between stimulation and recording was rationalized by a sheet conductor model. By combining a row of capacitors with a row of transistors we determined a simple stimulus–response matrix from CA3 to CA1. Possible contributions of inhomogeneities of synaptic projection, of tissue structure and of neuroelectronic interfacing were considered. The study provides the basis for a development of semiconductor chips with high spatial resolution that are required for long‐term studies of topographic mapping.
Correspondence of AQP4 expression and hypoxic‐ischaemic brain oedema monitored by magnetic resonance imaging in the immature and juvenile rat
Authors: Meng Shuzhen , Qiao Min , Lin Lily , Del Bigio Marc R. , Tomanek Boguslaw , Tuor Ursula I. 
Published: April 2004

AbstractWhether the water channel protein AQP4 is involved in the very early cell swelling and brain oedema observed with cerebral hypoxia–ischaemia (HI) and whether this response depends on the maturity of brain were investigated by comparing regional changes in AQP4 protein expression and signal intensity on magnetic resonance (MR) images in immature and juvenile brains. Maps of T2 and the apparent diffusion coefficient (ADC) of water were acquired in 1‐ and 4‐week‐old rats at times prior to HI, within the last 5 min of HI and 1 h or 24 h afterwards. AQP4 expression assessed with Western blotting was not significantly reduced until 24 h post‐HI irrespective of age. However, AQP4 immunostaining was decreased at the end of HI and at 1 h or 24 h after HI in the hemisphere ipsilateral to the occlusion with changes being similar in both age groups and coinciding well with regional reductions in ADC. IgG immunostaining to assess blood–brain barrier integrity and T2 were unchanged at early time points in 4‐week old rats despite decreases in AQP4 immunostaining. Thus, at early time points there were decreases in AQP4 detected with immunostaining but not Western blotting methods. However, the good correlation between alterations in ADC and AQP4 immunostaining suggests that changes in the AQP4 are involved in some of the early changes in brain water distribution observed in hypoxia‐ischemia, and supports the speculation that AQP4 is involved in the transport of water across the perivascular membranes into the vascular lumen.
In vivo effects of insulin‐like growth factor‐I (IGF‐I) on prenatal and early postnatal development of the central nervous system
Authors: Popken Gregory J. , Hodge Rebecca D. , Ye Ping , Zhang Jihui , Ng Winnie , O'Kusky John R. , D'Ercole A. Joseph 
Published: April 2004

AbstractThe in vivo actions of insulin‐like growth factor‐I (IGF‐I) on prenatal and early postnatal brain development were investigated in transgenic (Tg) mice that overexpress IGF‐I prenatally under the control of regulatory sequences from the nestin gene. Tg mice demonstrated increases in brain weight of 6% by embryonic day (E) 18 and 27% by postnatal day (P) 12. In Tg embryos at E16, the volume of the cortical plate was significantly increased by 52% and total cell number was increased by 54%. S‐phase labeling with 5‐bromo‐2′‐deoxyuridine revealed a 13–15% increase in the proportion of labeled neuroepithelial cells in Tg embryos at E14. In Tg mice at P12, significant increases in regional tissue volumes were detected in the cerebral cortex (29%), subcortical white matter (52%), caudate‐putamen (37%), hippocampus (49%), dentate gyrus (71%) and habenular complex (48%). Tg mice exhibited significant increases in the total number of neurons in the cerebral cortex (27%), caudate‐putamen (27%), dentate gyrus (69%), medial habenular nucleus (61%) and lateral habenular nucleus (36%). In the cerebral cortex and subcortical white matter of Tg mice, the total numbers of glial cells were significantly increased by 37% and 42%, respectively. The numerical density of apoptotic cells in the cerebral cortex, labeled by antibodies against active caspase‐3, was reduced by 26% in Tg mice at P7. Our results demonstrate that IGF‐I can both promote proliferation of neural cells in the embryonic central nervous system in vivo and inhibit their apoptosis during postnatal life.
Regulation of glutamate‐synthesizing enzymes by NMDA and potassium in cerebellar granule cells
Authors: Caballero‐Benítez Andrea , Alavez Silvestre , Uribe Rosa María , Morán Julio 
Published: April 2004

AbstractThe presence of 25 mm potassium (KCl) or N‐methyl‐d‐aspartate (NMDA) in cultured cerebellar granule neurons (CGN) induces a trophic effect, including a specific regulation of the enzymes involved in the glutamate neurotransmitter synthesis. In this study we explored the effect of these conditions on the cytosolic and mitochondrial isoenzymes of aspartate aminotransferase (AAT), and phosphate‐activated glutaminase (PAG) in CGN. We found that NMDA and KCl increased the AAT total activity by 40% and 70%, respectively. This effect was mediated by an augmentation in the protein levels (68% by NMDA, 58% by KCl). NMDA raised the Vmax and KCl raised both the maximol velocity (Vmax) and Michaelis constant (Km) of AAT. NMDA increased cytosolic AAT activity by 30% and mitochondrial activity by 70%; KCl increased cytosolic and mitochondrial AAT activity by 60% and 100%, respectively. This activation was also related to an increase in the protein levels. The effect of both conditions on the activity and protein levels were more pronounced in mitochondrial than cytosolic AAT and the increment elicited by KCl was higher in both isoforms than that produced by NMDA. The PAG and AAT mRNA levels were also regulated by incubation with NMDA and KCl similarly to the observed changes in the protein levels. These results suggest that NMDA receptor stimulation during CGN development differentially regulates the two AAT isoenzymes involved in the maturation of CGN and that the regulation of both AAT and PAG occurs also at the mRNA expression level, suggesting the involvement of a mechanism of gene expression regulation.
Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase‐3 protein expression in the mouse suprachiasmatic nuclei
Authors: Iwahana Eiko , Akiyama Masashi , Miyakawa Kazuko , Uchida Ayumi , Kasahara Jiro , Fukunaga Kohji , Hamada Toshiyuki , Shibata Shigenobu 
Published: April 2004

AbstractA circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase‐3 (GSK‐3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK‐3 protein expression. The decreased expression of GSK‐3 and increased expression of phosphorylated GSK‐3 (pGSK‐3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium‐treated mice housed under both light–dark and constant dark conditions. The enzyme activity of GSK‐3 in the SCN was low when the level of pGSK‐3 protein was high, as examined by immunoblotting analysis. Thus, GSK‐3 enzyme activity has a correlation with the expression of GSK‐3 protein in the SCN. Although both GSK‐3 and pGSK‐3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK‐3 protein and GSK‐3 activity in the SCN, we suggest that GSK‐3 plays a role in regulating the period of the mammalian circadian pacemaker.
Loss of GLUR2 α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid receptor subunit differentially affects remaining synaptic glutamate receptors in cerebellum and cochlear nuclei
Authors: Petralia Ronald S. , Sans Nathalie , Wang Ya‐Xian , Vissel Bryce , Chang Kai , Noben‐Trauth Konrad , Heinemann Stephen F. , Wenthold Robert J. 
Published: April 2004

AbstractThe α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid (AMPA) type of ionotropic glutamate receptor is the major mediator of fast neurotransmission in the brain and spinal cord. Most AMPA receptors are impermeable to calcium because they contain the GluR2 subunit. However, some AMPA receptors lack GluR2 and pass calcium which can mediate synaptic plasticity and, in excess, neurotoxicity. Previously, we showed a decrease in the density of synaptic AMPA receptors in the hippocampus of mice lacking GluR2. In this study, using these GluR2‐lacking mice, we examined other areas of the brain that differ in the amount of GluR2 normally present. Like hippocampal spines, cerebellar Purkinje spines normally express AMPA receptors with high GluR2 and showed a decrease in synaptic AMPA receptors in mutant mice. In contrast, neurons that normally express AMPA receptors with little or no GluR2, such as in the anteroventral cochlear nucleus, showed no decrease in AMPA receptors and even showed an increase in one AMPA receptor subunit. These two different patterns may relate to preadaptations to prevent calcium neurotoxicity; such mechanisms might be absent in Purkinje and hippocampal spines so that these neurons must decrease their total expression of synaptic AMPA receptors (calcium permeable in mutant mice) to prevent calcium neurotoxicity. In addition, we found that another glutamate receptor, GluRδ2, which is abundant only in parallel fibre synapses on Purkinje cells and in the dorsal cochlear nucleus, is up‐regulated at these synapses in mutant mice; this probably reflects some change in GluRδ2 targeting to these synapses.
Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus
Authors: Woda Alain , Blanc Olivier , Voisin Daniel L. , Coste Jérôme , Molat Jean‐Louis , Luccarini Philippe 
Published: April 2004

AbstractActivation of afferent nociceptive pathways is subject to activity‐dependent plasticity, which may manifest as windup, a progressive increase in the response of dorsal horn nociceptive neurons to repeated stimuli. At the cellular level, N‐methyl‐d‐aspartate (NMDA) receptor activation by glutamate released from nociceptive C‐afferent terminals is currently thought to generate windup. Most of the wide dynamic range nociceptive neurons that display windup, however, do not receive direct C‐fibre input. It is thus unknown where the NMDA mechanisms for windup operate. Here, using the Sprague–Dawley rat trigeminal system as a model, we anatomically identify a subpopulation of interneurons that relay nociceptive information from the superficial dorsal horn where C‐fibres terminate, to downstream wide dynamic range nociceptive neurons. Using in vivo electrophysiological recordings, we show that at the end of this pathway, windup was reduced (24 ± 6%, n = 7) by the NMDA receptor antagonist AP‐5 (2.0 fmol) and enhanced (62 ± 19%, n = 12) by NMDA (1 nmol). In contrast, microinjections of AP‐5 (1.0 fmol) within the superficial laminae increased windup (83 ± 44%, n = 9), whereas NMDA dose dependently decreased windup (n = 19).These results indicate that NMDA receptor function at the segmental level depends on their precise location in nociceptive neural networks. While some NMDA receptors actually amplify pain information, the new evidence for NMDA dependent inhibition of windup we show here indicates that, simultaneously, others act in the opposite direction. Working together, the two mechanisms may provide a fine tuning of gain in pain.
Dopamine receptor‐mediated regulation of RGS2 and RGS4 mRNA differentially depends on ascending dopamine projections and time
Authors: Taymans Jean‐Marc , Kia Hossein Kami , Claes Robby , Cruz Catarina , Leysen Josée ,   Xavier Langlois
Published: April 2004

AbstractRGS2 and RGS4 mRNAs are regulated in the rat striatum by dopaminergic agents. The present study further characterizes this regulation in three experiments. First, dopamine type 1 (receptor) (D1)‐ and dopamine type 2 (receptor) (D2)‐mediated regulator of G‐protein signalling (RGS) gene regulation was investigated in animals with deleted ascending dopaminergic pathways. We showed that RGS2 expression is controlled by D1 receptors either by direct action on D1 receptors or indirectly by presynaptic D2 receptors. Conversely, RGS4 gene expression is independent of presynaptic D2 receptors. Second, the study of colocalization between RGS2 or RGS4 and D1 or D2 by double labelling in situ hybridization histochemistry revealed broad expression of RGS2 and RGS4 mRNA in striatal subpopulations with colocalization of RGS2 and RGS4 with both D1 and D2 receptors. Finally, to test how far their gene regulation is temporally concerted, changes in RGS2 and RGS4 mRNA levels were measured in parallel with receptor occupancy by specific dopaminergic drugs at different time‐points. RGS2 was rapidly/transiently up‐regulated by the D1 agonist SKF82958 and the D2 antagonist haloperidol (peak at 0.5 h) and down‐regulated by the D1 antagonist SCH23390 and the D2 agonist quinpirole (trough at 1 and 2 h). RGS4 showed a delayed/transient up‐regulation with SCH23390 and quinpirole (peak at 4 and 2 h) and down‐regulation with haloperidol (trough at 8 h). Depending on the drug used, the degree of receptor occupancy did (D1 agonist and RGS2) or did not (D2 antagonist and RGS2) run parallel to RGS gene expression changes, indicating that certain drug effects are direct and others indirect. The precise control of RGS2 and RGS4 expression by dopamine receptors pleads in favour of their potential contribution to the fine‐tuning of D1 and D2 receptor signalling cascades.
Localized expression of amphiphysin Ir, a retina‐specific variant of amphiphysin I, in the ribbon synapse and its functional implication
Authors: Hosoya Osamu , Tsutsui Ken , Tsutsui Kimiko 
Published: April 2004

AbstractIn the vertebrate retina, presynaptic terminals of photoreceptors and bipolar cells form ribbon synapses and release neurotransmitter continuously. Endocytic machinery in the ribbon synapse is likely to differ from that in conventional synapses because of the much higher rate of synaptic vesicle recycling. However, protein components of the ribbon synapse identified so far are quite similar to those of the conventional synapses. Recently we identified amphiphysin I splice variants, termed amphiphysin Ir, that are transcribed specifically in retina from the authentic amphiphysin I gene [Y. Terada et al. (2002) FEBS Lett., 519, 185–190]. Amphiphysin I is a nerve terminal‐enriched protein, and involved in synaptic vesicle endocytosis as heterodimer with amphiphysin II, an isoform of amphiphysin I. We report here that the retina‐specific amphiphysin Ir is expressed exclusively in the ribbon synapse and not in conventional synapses. This is the first endocytosis‐related, ribbon synapse‐specific protein identified in the retina. By immunoprecipitation and double‐immunolabelling, amphiphysin Ir was shown to be associated not only with amphiphysin II, but also with dynamin, clathrin and α‐adaptin that are involved in synaptic vesicle recycling. The results suggest that endocytosis of the synaptic vesicle membrane in retinal ribbon synapses proceeds through a pathway similar to the one that is used in conventional synapses, although amphiphysin Ir is substituted for amphiphysin I. Amphiphysin Ir may play an essential role in the avid endocytic activity of ribbon synapses by associating with yet unknown protein partner(s) through its large insertional domain, which is absent from the conventional amphiphysin I.
Putative Physiological Significance of Vasopressin V1a Receptor Activation in Rat Pituicytes
Authors: Rosso L. , Peteri‐Brunbäck B. , Mienville J.‐M. 
Published: April 2004

AbstractPhysiological stimuli operative during, for example, dehydration or lactation, induce neurohypophysial astrocytes (pituicytes) to undergo reversible morphological changes, which in turn may modulate the release of vasopressin and oxytocin. To study the molecular mechanisms of this morphological plasticity, we used primary cultures of rat pituicytes. During stimulation with adenosine, pituicytes become stellate, which is characterized by a round, phase‐bright soma and complex arborization, implying major cytoskeletal modifications. Following addition of vasopressin or oxytocin, stellate pituicytes revert to a flat shape. The effects of both hormones are mediated by V1a receptor activation, which also induces biphasic Ca2+i signals in pituicytes. Stellation reversal requires Ca2+‐dependent activation of Cdc42, a small GTPase known to impact on the cytoskeleton. V1a receptor activation by vasopressin or oxytocin also stimulates [3H]taurine efflux from cultured pituicytes. As taurine inhibits vasopressin output from neurohypophysial terminals, we postulate a negative‐feedback mechanism whereby secreted vasopressin limits its own availability. This stop signal might be reinforced by shape changes elicited by vasopressin in pituicytes. These results support the concept that, during specific physiological states, pituicyte V1a receptor activation modulates the release of neurohypophysial hormones.
The Role of Vasopressin in the Genetic and Neural Regulation of Monogamy
Authors: Lim M. M. , Hammock E. A. D. , Young L. J. 
Published: April 2004

AbstractArginine vasopressin modulates pairbond formation in the monogamous prairie vole (Microtus ochrogaster). Our laboratory has investigated the genetic and neural mechanisms by which vasopressin and its V1a receptor (V1aR) regulate social attachment between mates. Non‐monogamous vole species show strikingly different distribution patterns of brain V1aR expression compared to monogamous species, and these patterns are thought to arise from species differences in the respective promoter sequences of the V1aR gene. Individual differences in prairie vole V1aR patterns may also reflect individual differences in promoter sequences. Pharmacological and genetic manipulation of the specific brain regions that express V1aR in the ‘monogamous pattern’ allows multilevel examination of the neural circuits that underlie pairbond formation in monogamous species. For example, V1aR are expressed in brain regions involved in reward circuitry in monogamous vole species and have been implicated in pairbonding. V1aR are also highly expressed in regions implicated in the olfactory processing of sociosexual behaviour. We hypothesize that both circuits of reward and olfactory memory underlie the cognitive mechanisms that control pairbonding. When used in conjuction, genetic and cellular analyses of a complex social behaviour can provide a coherent framework with which to examine the role of the vasopressin system in species evolution and neural control of behaviour.
Steroid‐Independent Regulation of Uterine Oxytocin Receptors
Authors: Siebel A. L. , Gehring H. M. , Parry L. J. 
Published: April 2004

AbstractThe oxytocin receptor is an important contractile‐associated protein, up‐regulated at term in the myometrium in many mammalian species. We conducted studies in a novel animal model to challenge the general view that gonadal steroids are a major regulatory factor of uterine oxytocin receptors. Female marsupials have separate uteri and, in monovular species such as the tammar wallaby, the conceptus is present in one uterus whereas the contralateral uterus is empty. A marked increase in myometrial oxytocin receptors occurs only in the gravid uterus. Fetectomy experiments demonstrated that local embryo‐derived factors stimulate this gravid uterus‐specific increase in oxytocin receptors, and that uterine distension is probably not a key component in this regulatory pathway. Unilateral ovariectomy has no significant effect on uterine oxytocin receptors, emphasizing the impact of the conceptus on oxytocin receptor regulation and the minimal influence of gonadal steroids on parturition in this species. Our data highlight that regulation of uterine oxytocin receptor expression is multifactorial, and does not necessarily rely on gonadal steroids.
Functional Genomics of Social Recognition
Authors: Choleris E. , Kavaliers M. , Pfaff D. W. 
Published: April 2004

AbstractAlthough various types of group living are widespread in mammals, including humans, the study of the hormonal and genetic underpinnings of nonsexual social behaviour, is in its infancy compared to the analysis of sexual behaviour mechanisms. Oxytocin, vasopressin and gonadal hormones certainly play an important role. Social recognition, where animals identify and recognize other individual conspecifics, is a crucial prerequisite for the occurrence of a wide range of social behaviours. Social recognition is also important for coping with one major cost of life in a group: the increased risk of exposure to parasites and infection. We review recent functional genomic studies on the involvement of oxytocin and oestrogen‐receptor genes in the regulation of social recognition in mice and in the ecologically relevant context of parasite recognition and avoidance. Based on quantitative studies of social recognition with gene‐knockout mice and with antisense DNA, we propose a four‐gene micronet contributing to social recognition. This micronet involves the genes coding for oestrogen receptors alpha (ER‐α), beta (ER‐β), oxytocin and the oxytocin receptor. In this model, circulating oestrogens promote transcription of (i) oxytocin in the paraventricular nucleus of the hypothalamus through ER‐β and (ii) oxytocin receptor in the amygdala through ER‐α. This model forms the core around which increasingly complex genetic, hormonal and neural interactions associated with social behaviours and recognition can be organized.
Magnocellular Dendrites: Prototypic Receiver/Transmitters
Authors: Morris J. F. , Ludwig M. 
Published: April 2004

AbstractThe hypothalamic magnocellular neurones of the supraoptic and paraventricular nuclei of mammals are among the best understood of all peptidergic neurones, and therefore serve as a model for understanding the functions of other peptidergic neurones. The release of vasopressin‐ and oxytocin‐containing neurosecretory vesicles from their dendrites was first established 15 years ago. This local release is now known to have many functions, including controlling the interactions between oxytocin neurones and their surrounding glia, and facilitating and inhibiting the electrical activation of the neurones. Technical advances now permit dynamic analysis of dendritic release. Here, we review recent studies that focus on the conditional priming of dendritic peptide release by peptide‐induced liberation of intracellular calcium, and the role of dendritic protein synthesis in the dendritic peptide release and the control of receptive properties of the neurones.