bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of the glutamate receptor ε2 and δ2 subunits in the potentiation and prepulse inhibition of the acoustic startle reflex
Authors: Takeuchi Tomonori , Kiyama Yuji , Nakamura Kazuhiro , Tsujita Mika , Matsuda Ikuo , Mori Hisashi , Munemoto Yumi , Kuriyama Hiromichi , Natsume Rie , Sakimura Kenji , Mishina Masayoshi 
Published: March 2003

AbstractWe examined the regulation of the acoustic startle response in mutant mice of the N‐methyl‐d‐aspartate (NMDA)‐ and δ‐subtypes of the glutamate receptor (GluR) channel, which play important roles in neural plasticity in the forebrain and the cerebellum, respectively. Heterozygous mutant mice with reduced GluRε2 subunits of the NMDA receptor showed strongly enhanced startle responses to acoustic stimuli. On the other hand, heterozygous and homozygous mutation of the other NMDA receptor GluRε subunits exerted no, or only small effects on acoustic startle responses. The threshold of the auditory brainstem response of the GluRε2‐mutant mice was comparable to that of the wild‐type littermates. The primary circuit of the acoustic startle response is a relatively simple oligosynaptic pathway located in the lower brainstem, whilst the expression of GluRε2 is restricted to the forebrain. We thus suggest that the NMDA receptor GluRε2 subunit plays a role in the regulation of the startle reflex. Ablation of the cerebellar Purkinje cell‐specific δ2 subunit of the GluR channel exerted little effect on the acoustic startle response but resulted in the enhancement of prepulse inhibition of the reflex. Because inhibition of the acoustic startle response by a weak prepulse is a measure of sensorimotor gating, the process by which an organism filters sensory information, these observations indicate the involvement of the cerebellum in the modulation of sensorimotor gating.
Cellular and subcellular morphological localization of normal prion protein in rodent cerebellum
Authors: Lainé Jeanne , Marc Marie‐Elizabeth , Sy Man‐Sun , Axelrad Herbert 
Published: March 2003

AbstractNormal cellular prion protein, a necessary protagonist in fatal neurodegenerative prion diseases, was mapped in rodent cerebellum to establish its cellular and ultrastuctural localization. Existing morphological data about native prion protein distribution in brain tissues remain, indeed, contradictory and do not fit with biochemical and cell biological results. Using ultrastructural preembedding immunocytochemistry and a monoclonal anti‐mouse prion protein antibody, this report shows that cellular prion protein is present in all cortico‐cerebellar and deep nuclei neuronal cell types, as well as in all glial cell types. The heaviest expression appears on parallel fibres and astrocytic processes. The protein is exclusively located on the outer cell membrane and in Golgi and endosomal intracytoplasmic organelles, with no cytoplasmic or synaptic vesicle labelling. Most important, and in contrast with previous ultrastructural data, cellular prion protein is shown to be distributed on all portions of neurons, without any preferential synaptic targeting. The present morphological report shows, for the first time in vivo, that the cellular prion protein is present on the entire cell surface membrane of all neuronal and glial cell types of the rat cerebellum. This ubiquitous presence supports the notion that prion protein has a generalized cellular function in brain tissue rather than a specialized role restricted to synaptic transmission.
Purification of Purkinje cells by fluorescence‐activated cell sorting from transgenic mice that express green fluorescent protein
Authors: Tomomura Mineko , Rice Dennis S. , Morgan James I. , Yuzaki Michisuke 
Published: March 2003

AbstractThe cerebellar Purkinje cell has been the focus of numerous studies involving the analysis of development and information processing in the nervous system. Purkinje cells represent less than 0.1% of the total cell content of the cerebellum. To facilitate studies of molecules that are expressed in such a small proportion of neurons, we have established procedures for the purification of these cells. Transgenic mice were developed in which the expression of green fluorescent protein (GFP) was controlled by the L7 promoter. In adult cerebellum, GFP fluorescence was only detected in Purkinje cells, where it filled dendrites, soma and axons. GFP fluorescence was detected in Purkinje cells as early as embryonic day 17 and increased during development in vivo and in dissociated cerebellar culture. Mirroring endogenous L7 expression, high levels of GFP were observed in retinal rod bipolar cells. Lower levels of GFP were seen in olfactory periglomerular cells, neurons in the interpeduncular nucleus, and superior colliculus neurons. Cerebella from transgenic mice were dissociated by mild enzymatic treatment and Purkinje cells were isolated by fluorescence‐activated cell sorting (FACS). By selecting optimal parameters, a fraction of viable Purkinje cells that was 94% pure was obtained. These results indicate that FACS is a powerful tool for isolating Purkinje cells from postnatal L7‐GFP transgenic mice. GFP‐positive neurons will also be useful in the real‐time observation of dendritic morphogenesis and axonal outgrowth during development, or after neuronal activity in vitro.
Fos imaging reveals differential neuronal activation of areas of rat temporal cortex by novel and familiar sounds
Authors: Wan H. , Warburton E. C. , Kuśmierek P. , Aggleton J. P. , Kowalska D. M. , Brown M. W. 
Published: March 2003

AbstractTo provide information about the possible regions involved in auditory recognition memory, this study employed an imaging technique that has proved valuable in the study of visual recognition memory. The technique was used to image populations of neurons that are differentially activated by novel and familiar auditory stimuli, thereby paralleling previous studies of visual familiarity discrimination. Differences evoked by novel and familiar sounds in the activation of neurons were measured in different parts of the rat auditory pathway by immunohistochemistry for the protein product (Fos) of the immediate early gene c‐fos. Significantly higher counts of stained neuronal nuclei (266 ± 21/mm2) were evoked by novel than by familiar sounds (192 ± 17/mm2) in the auditory association cortex (area Te3; AudA). No such significant differences were found for the inferior colliculus, primary auditory cortex, postrhinal cortex, perirhinal cortex (PRH), entorhinal cortex, amygdala or hippocampus. These findings are discussed in relation to the results of lesion studies and what is known of areas involved in familiarity discrimination for visual stimuli. Differential activation is produced by novel and familiar individual stimuli in sensory association cortex for both auditory and visual stimuli, whereas the PRH is differentially activated by visual but not auditory stimuli. It is suggested that this latter difference is related to the nature of the particular auditory and visual stimuli used.
Receptive field organization of disparity‐sensitive cells in Macaque medial superior temporal cortex
Authors: Gonzalez Francisco , Perez Rogelio , Justo Maria S. , Bermudez Maria A. 
Published: March 2003

AbstractBinocular disparities are crucial for building an accurate three‐dimensional representation of the peripersonal environment in a viewer‐centred frame of reference. Previous studies have shown that visual cells of the medial superior temporal cortex (MST) have large receptive fields and that they are sensitive to disparities present in large surfaces. By using a reverse cross‐correlation technique in this study we tested 175 disparity‐sensitive units recorded from MST in the awake Macaca mulatta monkey to determine if these large receptive fields are homogeneous in terms of disparity sensitivity. We found that the receptive fields of 50 cells (50 out of 175, 29%) showed subregions with specific disparity sensitivity. These subregions presented eccentricities from 0.8 to 22.3° and their sizes varied from 1.6 to 15.3°2. This particular receptive field organization represents a suitable mechanism for encoding the location of small objects within our peripersonal space.
Analysis of cell signalling in the rodent pineal gland deciphers regulators of dynamic transcription in neural/endocrine cells*
Authors: Stehle Jörg H. , Von Gall Charlotte , Korf Horst‐Werner 
Published: March 2003

AbstractIn neurons, a temporally restricted expression of cAMP‐inducible genes is part of many developmental and adaptive processes. To understand such dynamics, the neuroendocrine rodent pineal gland provides an excellent model system as it has a clearly defined input, the neurotransmitter norepinephrine, and a measurable output, the hormone melatonin. In this system, a regulatory scenario has been deciphered, wherein cAMP‐inducible genes are rapidly activated via the transcription factor phosphoCREB to induce transcriptional events necessary for an increase in hormone synthesis. However, among the activated genes is also the inhibitory transcription factor ICER. The increasing amount in ICER protein leads ultimately to the termination of mRNA accumulation of cAMP‐inducible genes, including the gene for the Aa‐nat that controls melatonin production. This shift in ratio of phosphoCREB and ICER levels that depends on the duration of stimulation can be interpreted as a self‐restriction of cellular responses in neurons and has also been demonstrated to interfere with cellular plasticity in many non‐neuronal systems.
Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve
Authors: Buyse Marion , Ovesjö Marie‐Louise , Goïot Hélène , Guilmeau Sandra , Péranzi Gabriel , Moizo Laurent , Walker Francine , Lewin Miguel J. M. , Meister Björn , Bado André 
Published: March 2003

AbstractLeptin, the product of the ob gene, plays a key role in the regulation of food intake via a cross‐talk between hypothalamic leptin receptors and neuropeptides that affect feeding behaviour. Recent studies have shown a synergistic interaction between leptin and cholecystokinin (CCK) leading to suppression of food intake, which involves CCK‐1 receptors and capsaicin‐sensitive vagal fibres. In this study, we have investigated the presence of leptin receptors in afferent and efferent neurons of the vagus nerve. By using reverse transcription‐polymerase chain reaction, mRNAs encoding long (Ob‐Rb) and short (Ob‐Ra) leptin receptor isoforms were detected in the rat nodose ganglion, which contains the cell bodies of the vagal afferent neurons. Western blot analysis confirmed the presence of leptin receptor‐immunoreactive proteins in extracts from the vagal trunk. Immunohistochemistry showed the presence of leptin receptors and the leptin‐induced transcription factor STAT3 in the cytoplasm of nodose ganglion cells. In cervical vagal segments, levels of leptin receptor protein displayed physiological regulation, with decreased amounts after feeding and increased levels after food restriction. In addition, leptin receptor and STAT3 immunoreactivities were detected in neurons of the nucleus of tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) by immunofluorescence histochemistry. Furthermore, direct double‐labelling demonstrated colocalization of Ob‐Rb and STAT3 immunoreactivities in cholinergic vagal efferent cell bodies of the DMNX. It is speculated that vagal leptin receptors, apart from being activated by adipocyte‐derived leptin, may also be influenced by leptin produced by the stomach. This may explain the synergistic action of leptin and CCK on neuronal activity in the NTS and on food intake.
Chronic psychosocial stress differentially affects apoptosis in hippocampal subregions and cortex of the adult tree shrew
Authors: Lucassen Paul J. , Vollmann‐Honsdorf Gesa K. , Gleisberg Mira , Czéh Boldizsár , De Kloet E. Ron , Fuchs Eberhard 
Published: March 2003

AbstractWe studied the effect of chronic psychosocial stress on cell death and volume changes in the tree shrew hippocampus. In situ end labelling (ISEL) identified low frequent but convincing apoptosis in many hippocampal subregions. Also in entorhinal cortex, apoptosis was found, generally at higher frequencies. After 28 days of chronic stress, apoptosis was significantly reduced in the CA1 stratum radiatum, whereas an increase was observed in the hilus (P < 0.04). With all subregions taken together, the hippocampus showed a decrease, whereas in the cortex, an increase in apoptosis was found after stress (P < 0.04). In a parallel and similar chronic stress study, post mortem morphometry of the same brain regions was performed, revealing mild decreases (7.6%) in entire hippocampal volume. We conclude that (i) low frequent apoptosis occurs throughout the adult tree shrew brain, and (ii) 28 days of chronic stress differentially affects its occurrence in distinct hippocampal subregions and entorhinal cortex. As previous stereological investigations failed to detect any loss in the principal neuronal layers, psychosocial stress, therefore, must affect other (structural) parameters like dendritic tree, interneurons, neurogenesis, or glia.
Ca2+‐dependent regulation of synaptic δ2 glutamate receptor density in cultured rat Purkinje neurons
Authors: Hirai Hirokazu 
Published: March 2003

AbstractThe δ2 glutamate receptor (δ2 receptor), which is expressed abundantly at parallel fibre–Purkinje neuron synapses, has an important role in synaptogenesis and synaptic plasticity in the cerebellum. The present study examined the molecular mechanisms regulating synaptic δ2 receptor density. Immunocytochemistry, using two antibodies against the intracellular C‐terminal and extracellular N‐terminal regions of the δ2 receptor, indicated the reversible redistribution of postsynaptic δ2 receptors in response to either glutamatergic stimulation or enhancement of synaptic activity. The effect of glutamatergic stimulation was completely inhibited by either coapplication of the glutamate receptor antagonist or the removal of extracellular Ca2+ using EGTA and mimicked by selective activation of voltage‐gated Ca2+ channels (VGCCs) with KCl, suggesting the significant role of Ca2+ influx in δ2 receptor redistribution. Biochemical examination indicated that a large amount of δ2 receptor protein was internalized following glutamatergic stimulation. These results suggest that the number of synaptic δ2 receptors is controlled by endocytosis in a synaptic activity‐ and intracellular Ca2+‐dependent way, through which synaptogenesis and synaptic plasticity in Purkinje cells might be modulated.
Activation of muscarinic receptors induces protein synthesis‐dependent long‐lasting depression in the perirhinal cortex
Authors: Massey P. V. , Bhabra G. , Cho K. , Brown M. W. , Bashir Z. I. 
Published: March 2003

AbstractThere is strong evidence that decrements in neuronal activation in perirhinal cortex when a novel stimulus is repeated provide a neural substrate of visual recognition memory. There is also strong evidence that muscarinic acetylcholine (ACh) receptors are involved in learning and memory. However, the mechanisms underlying neuronal decrements in the perirhinal cortex and the basis of ACh involvement in learning and memory are not understood. In an in vitro preparation of rat perirhinal cortex we now demonstrate that activation of ACh receptors by carbachol (CCh) produces long‐lasting depression (LLD) of synaptic transmission that is dependent on muscarinic M1 receptor activation. Crucially, the induction of this form of LLD requires neither N‐methyl‐d‐aspartate receptor activation nor synaptic stimulation. CCh‐induced LLD was not blocked by the protein kinase C inhibitors staurosporine or BIM, or by the protein phosphatase inhibitor okadaic acid. However, each of cyclopiazonic acid (an agent that depletes intracellular calcium stores) and anisomycin (an inhibitor of protein synthesis) significantly reduced the magnitude of CCh‐induced LLD. These mechanisms triggered by muscarinic receptor activation could play a role in the induction and/or expression of certain forms of activity‐dependent long‐term depression in perirhinal cortex. An understanding of CCh‐induced LLD may thus provide clues to the mechanisms underlying lasting neuronal decrements that occur in the perirhinal cortex and hence for neural substrates of visual recognition memory.
Fluorescent tracer in pilocarpine‐treated rats shows widespread aberrant hippocampal neuronal connectivity
Authors: Lehmann T.‐N. , Gabriel S. , Eilers A. , Njunting M. , Kovacs R. , Schulze K. , Lanksch W. R. , Heinemann U. 
Published: March 2003

AbstractNeuronal fibres of the hippocampal formation of normal and chronic epileptic rats were investigated by fluorescent tracing methods using the pilocarpine model of limbic epilepsy. Two months after onset of spontaneous limbic seizures, hippocampal slices were prepared and maintained in vitro for 10 h. Small crystals of fluorescent dye [fluorescein (fluoro‐emerald®) and tetramethylrhodamine (fluoro‐ruby®)] were applied to different hippocampal regions. The main findings were: (i) in control rats there was no supragranular labelling when the mossy fibre tract was stained in stratum radiatum of area CA3. However, in epileptic rats a fibre network in the inner molecular layer of the dentate gyrus was retrogradely labelled; (ii) a retrograde innervation of area CA3 by CA1 pyramidal cells was disclosed by labelling remote CA1 neurons after dye injection into the stratum radiatum of area CA3 in chronic epileptic rats; (iii) labelling of CA1 neurons apart from the injection site within area CA1 was observed in epileptic rats but not in control animals; and (iv), a subicular‐hippocampal projection was present in pilocarpine‐treated rats when the tracer was injected just below the stratum pyramidale of area CA1. The findings show that fibre rearrangement in distinct regions of the epileptic hippocampal formation can occur as an aftermath of pilocarpine‐induced status epilepticus.
An essential role for the H218/AGR16/Edg‐5/LPB2 sphingosine 1‐phosphate receptor in neuronal excitability
Authors: MacLennan A. John , Carney Paul R. , Zhu Wei Jian , Chaves Alicia H. , Garcia Jairo , Grimes Jeremy R. , Anderson Kevin J. , Roper Steven N. , Lee Nancy 
Published: March 2003

AbstractA wealth of indirect data suggest that the H218/AGR16/Edg‐5/LPB2 sphingosine 1‐phosphate (S1P) receptor plays important roles in development. In vitro, it activates several forms of development‐related signal transduction and regulates cellular proliferation, differentiation and survival. It is expressed during embryogenesis, and mutation of an H218‐like gene in zebrafish leads to profound defects in embryonic development. Nevertheless, the in vivo functions served by H218 signalling have not been directly investigated. We report here that mice in which the H218 gene has been disrupted are unexpectedly born with no apparent anatomical or physiological defects. In addition, no abnormalities were observed in general neurological development, peripheral axon growth or brain structure. However, between 3 and 7 weeks of age, H218–/– mice have seizures which are spontaneous, sporadic and occasionally lethal. Electroencephalographic abnormalities were identified both during and between the seizures. At a cellular level, whole‐cell patch‐clamp recordings revealed that the loss of H218 leads to a large increase in the excitability of neocortical pyramidal neurons. Therefore, H218 plays an essential, unanticipated and functionally important role in the proper development and/or mediation of neuronal excitability.
Spatiotemporal characterization of rhythmic activity in rat spinal cord slice cultures
Authors: Tscherter Anne , Heuschkel Marc O. , Renaud Philippe , Streit Jürg 
Published: March 2003

AbstractRat spinal networks generate a spontaneous rhythmic output directed to motoneurons under conditions of increased excitation or of disinhibition. It is not known whether these differently induced rhythms are produced by a common rhythm generator. To investigate the generation and the propagation of rhythmic activity in spinal networks, recordings need to be made from many neurons simultaneously. Therefore extracellular multisite recording was performed in slice cultures of embryonic rat spinal cords grown on multielectrode arrays. In these organotypic cultures most of the spontaneous neural activity was nearly synchronized. Waves of activity spread from a source to most of the network within 35–85 ms and died out after a further 30–400 ms. Such activity waves induced the contraction of cocultured muscle fibres. Several activity waves could be grouped into aperiodic bursts. Disinhibition with bicuculline and strychnine or increased excitability with high K+ or low Mg2+ solutions could induce periodic bursting with bursts consisting of one or several activity waves. Whilst the duration and period of activity waves were similar for all protocols, the duration and period of bursts were longer during disinhibition than during increased excitation. The sources of bursting activity were mainly situated ventrally on both sides of the central fissure. The pathways of network recruitment from one source were variable between bursts, but they showed on average no systematic differences between the protocols. These spatiotemporal similarities under conditions of increased excitation and of disinhibition suggest a common spinal network for both types of rhythmic activity.
The generation of rhythmic activity in dissociated cultures of rat spinal cord
Authors: Streit Jürg , Tscherter Anne , Heuschkel Marc O. , Renaud Philippe 
Published: March 2003

AbstractLocomotion in vertebrates is controlled by central pattern generators in the spinal cord. The roles of specific network architecture and neuronal properties in rhythm generation by such spinal networks are not fully understood. We have used multisite recording from dissociated cultures of embryonic rat spinal cord grown on multielectrode arrays to investigate the patterns of spontaneous activity in randomised spinal networks. We were able to induce similar patterns of rhythmic activity in dissociated cultures as in slice cultures, although not with the same reliability and not always with the same protocols. The most reliable rhythmic activity was induced when a partial disinhibition of the network was combined with an increase in neuronal excitability, suggesting that both recurrent synaptic excitation and neuronal excitability contribute to rhythmogenesis. During rhythmic activity, bursts started at several sites and propagated in variable ways. However, the predominant propagation patterns were independent of the protocol used to induce rhythmic activity. When synaptic transmission was blocked by CNQX, APV, strychnine and bicuculline, asynchronous low‐rate activity persisted at ≈ 50% of the electrodes and ≈ 70% of the sites of burst initiation. Following the bursts, the activity in the interval was transiently suppressed below the level of intrinsic activity. The degree of suppression was proportional to the amount of activity in the preceding burst. From these findings we conclude that rhythmic activity in spinal cultures is controlled by the interplay of intrinsic neuronal activity and recurrent excitation in neuronal networks without the need for a specific architecture.