bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of the learning and plasticity‐associated gene Zif268 following exposure to a discrete cocaine‐associated stimulus
Authors: Thomas Kerrie L. , Arroyo Mercedes , Everitt Barry J. 
Published: May 2003

AbstractWe investigated whether the expression of the plasticity‐associated gene, zif268, was associated with memories retrieved by exposure to a discrete stimulus that had been associated with cocaine, either self‐administered or administered noncontingently. In the absence of drug, passive presentation of a cocaine‐associated light stimulus induced changes in the expression of zif268 measured by in situ hybridization within a limbic cortical–ventral striatal circuit that was not only regionally selective but related to whether the rats had originally received response‐contingent or noncontingent stimulus‐drug pairings. In rats that had self‐administered drug, the cocaine–conditioned stimulus (CS) increased zif268 expression in neurons of the ventral tegmental area, nucleus accumbens core and shell, and basal nucleus of the amygdala but not hippocampus, prelimbic area of the medial prefrontal cortex or amygdala central nucleus. The same CS that had been associated with cocaine administered noncontingently additionally increased zif268 mRNA levels in area Cg1 of the anterior cingulate cortex, ventral and lateral regions of the orbitofrontal cortex and lateral nucleus of the amygdala. Zif268 induction was related to the predictive relationship between the stimulus and cocaine as no changes were seen in cocaine‐experienced rats that had received unpaired light and drug presentations during training. Thus, zif268 expression is increased by appetitively (drug) conditioned stimuli after Pavlovian learning. Zif268 may participate in the molecular mechanisms underlying the reconsolidation or re‐encoding of Pavlovian stimulus–drug associations across a distributed limbic cortical‐ventral striatal neural network and that may contribute to the basis of the enduring drug‐seeking behaviour produced by environmental cues.
Regulation of α1G T‐type calcium channel gene (CACNA1G) expression during neuronal differentiation
Authors: Bertolesi Gabriel E. , Jollimore Christine A. B. , Shi Chanjuan , Elbaum Lindsy , Denovan‐Wright Eileen M. , Barnes Steven , Kelly Melanie E. M. 
Published: May 2003

AbstractDown‐regulation of T‐type Ca channel current and mRNA occurs following differentiation of Y79 retinoblastoma cells. To understand how the decrease in expression is linked to cell differentiation, we examined transcriptional regulation of the Cav3.1 Ca channel gene, CACNA1G. We identified two putative promoters (A and B) in 1.3 kb of cloned genomic DNA. Reverse transcriptase‐polymerase chain reaction and 5′ rapid amplification of cDNA ends‐polymerase chain reaction analyses demonstrated that two transcripts with different 5′ untranslated regions are generated by different transcription start sites, with promoter A favoured in undifferentiated cells and promoter B favoured in differentiated cells. Functional analyses of the promoter sequence revealed that both promoters are active. Enhancer and repressor sequences were identified upstream of promoter A and B, respectively. These results suggest that the down‐regulation of α1G mRNA in differentiated Y79 cells is mediated primarily by decreased activity of promoter A, which could occur in conjunction with repression of the activity of promoter B. The decrease in T‐type Ca channel expression in Y79 cells may be an essential signal affecting phenotypic maturation and expression of other ion channel subtypes in the differentiated cells.
Rhythm sequence through the olfactory bulb layers during the time window of a respiratory cycle
Authors: Buonviso Nathalie , Amat Corine , Litaudon Philippe , Roux Stephane , Royet Jean‐Pierre , Farget Vincent , Sicard Gilles 
Published: May 2003

AbstractThe mammalian olfactory bulb is characterized by prominent oscillatory activity of its local field potentials. Breathing imposes the most important rhythm. Other rhythms have been described in the β‐ and γ‐frequency ranges. We recorded unitary activities in different bulbar layers simultaneously with local field potentials in order to examine the different relationships existing between (i) breathing and field potential oscillations, and (ii) breathing and spiking activity of different cell types. We show that, whatever the layer, odour‐induced γ oscillations always occur around the transition point between inhalation and exhalation while β oscillations appear during early exhalation and may extend up to the end of inhalation. By contrast, unitary activities exhibit different characteristics according to the layer. They vary in (i) their temporal relationship with respect to the respiratory cycle; (ii) their spike rates; (iii) their temporal patterns defined according to the respiratory cycle. The time window of a respiratory cycle might thus be split into three main epochs based on the deceleration of field potential rhythms (from γ to β oscillations) and a simultaneous gradient of spike discharge frequencies ranging from 180 to 30 Hz. We discuss the possibility that each rhythm could serve different functions as priming, gating or tuning for the bulbar network.
Deficit in long‐term contextual fear memory induced by blockade of β‐adrenoceptors in hippocampal CA1 region
Authors: Ji Jin‐Zhao , Wang Xin‐Ming , Li Bao‐Ming 
Published: May 2003

AbstractThe present study investigated the effects of intra‐CA1 infusion of d,l‐propranolol, the β‐adrenergic antagonist, on memory for contextual fear conditioning. d,l‐Propranolol administered 5 min (‘0 h’) postconditioning impaired long‐term but not short‐term contextual fear memory, while it was ineffective when administered 6 h postconditioning, suggesting that there is a time window for β‐adrenoceptors to play a role. Thus, we conclude that β‐adrenoceptors in area CA1 are involved in regulating consolidation of contextual fear memory, with ‘0 h’ but not 6 h post‐training, a sensitive time point for the β‐adrenergic involvement.
Impaired glutamate uptake and EAAT2 downregulation in an enterovirus chronically infected human glial cell line
Authors: Legay Vincent , Deleage Christelle , Beaulieux Frederik , Giraudon Pascale , Aymard Michelle , Lina Bruno 
Published: May 2003

AbstractRapid and efficient uptake of glutamate via the high‐affinity glutamate transporter EAAT2 is important for limiting glutamate‐mediated excitotoxicity involved in neuronal death. Furthermore, there is evidence of altered glutamate uptake and catabolism in motor neuron diseases. Such a defect has been reported in amyotrophic lateral sclerosis, the major motor neuron disease, and was associated with impairment in EAAT2 processing. We recently reported the presence of enterovirus genome specifically in the anterior horn of amyotrophic lateral sclerosis cases, suggesting the involvement of a chronic/persistent enterovirus infection in amyotrophic lateral sclerosis. To investigate a putative link between enterovirus infection and the glutamate‐mediated excitotoxicity observed in amyotrophic lateral sclerosis, we developed an in vitro model consisting of a human glial cell line infected with ECHOvirus 6, one of the enteroviruses with sequences closely related to those detected in patients with amyotrophic lateral sclerosis. In these glial cells, an ECHOvirus 6 chronic infection was established, resulting in altered extracellular glutamate uptake. This correlated with an aberrant splicing of the EAAT2 pre‐messenger ribonucleic acid and a significant loss of EAAT2 protein expression, similar to that observed in patients with amyotrophic lateral sclerosis. These results provide convincing evidence that an enterovirus chronic/persistent infection may alter glial glutamate uptake and catabolism. As enteroviruses are extremely common human pathogens, they may act as a trigger in the development of certain motor neuron diseases, such as amyotrophic lateral sclerosis.
Chronic unpredictable stress impairs long‐term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro
Authors: Alfarez Deborah N. , Joëls Marian , Krugers Harm J. 
Published: May 2003

AbstractRises in corticosteroid levels, e.g. after acute stress, impair synaptic plasticity in the rat hippocampus when compared with the situation where levels are basal, i.e. under rest. We here addressed the question whether basal and raised levels of corticosterone affect synaptic plasticity similarly in animals that experienced chronic stress prior to corticosterone application. To this end, rats were exposed to a 21‐day variable stress paradigm. Synaptic plasticity was examined in vitro in the dentate gyrus and CA1 hippocampal region, 24 h after exposure to the last stressor, i.e. when corticosterone levels are basal (low). First we observed that long‐term potentiation was greatly impaired in both CA1 and dentate gyrus after 3 weeks of exposure to variable stress, when recorded under conditions where plasma corticosterone levels are low. Second, administration of 100 nm corticosterone in vitro reduced synaptic plasticity in CA1 of control rats, but induced no further impairment of synaptic plasticity in chronically stressed rats. Third, in the dentate gyrus, corticosterone incubation did not affect synaptic plasticity in slices from both control and stressed animals. We conclude that: (i) exposure to chronic variable stress per se reduces synaptic plasticity both in CA1 and dentate gyrus; and (ii) acute rises in corticosterone level induce no additional impairment of synaptic plasticity in the CA1 region of chronically stressed rats. It is tempting to speculate that the stress‐induced reduction of hippocampal efficacy provides a cellular substrate for cognitive deficits in hippocampus‐dependent learning tasks seen after prolonged exposure to stressful events.
Reduced spinal cord sensitization to C‐fibre stimulation in mice over‐expressing galanin
Authors: Grass Stefan , Crawley Jacqueline N. , Xu Xiao‐Jun , Wiesenfeld‐Hallin Zsuzsanna 
Published: May 2003

AbstractThe neuropeptide galanin may have a role in spinal nociception. In this study, we examined the excitability of the flexor reflex and its sensitization by repetitive stimulation of nociceptive C‐fibres in anaesthetized mice that over‐express galanin. No difference was seen between over‐expressing galanin and wild‐type mice in the magnitude of the baseline flexor reflex. Repetitive conditioning stimulation of C‐fibres (10 stimuli at 1 Hz) produced a gradual increase in reflex magnitude during the conditioning stimulation (wind‐up), as well as an increase in spinal reflex excitability after the termination of the stimulus train (central sensitization) in wild‐type mice. Although the wind‐up did not differ between over‐expressing galanin and wild‐type mice, the magnitude of central sensitization was significantly reduced in the over‐expressing galanin mice (24 ± 13% peak increase compared with 164 ± 65% in the wild‐type). Intrathecal administration of M35, a galanin receptor antagonist, markedly enhanced central sensitization in over‐expressing galanin mice in association with C‐fibre conditioning stimulation, while having no effect in wild‐type mice. These results provide further electrophysiological evidence for an inhibitory function of galanin in modulation of central sensitization in response to C‐fibre stimulation.
Morphological changes in hippocampal dentate gyrus synapses following spatial learning in rats are transient
Authors: Eyre Mark D. , Richter‐Levin Gal , Avital Avi , Stewart Michael G. 
Published: May 2003

AbstractThe hippocampus is believed to play a crucial role in the formation of memory for spatial tasks. In the present study quantitative electron microscopy was used to investigate morphological changes in the hippocampal dentate gyrus of 3‐month‐old male rats at 3, 9 and 24 h after training to find a hidden platform in a Morris water maze. Average escape latency (time taken to reach the platform) in all trained groups decreased progressively with increased training but data from a probe trial (quadrant analysis test) at the end of training indicated that only animals in the 9‐ and 24‐h groups, not the 3‐h group, displayed significant retention of platform location. Unbiased stereological methods were used to estimate synapse and neuronal density at each time point after training. The majority of synapses had unperforated postsynaptic densities, were localized on small dendritic spines and were classed as axo‐spinous. In comparison to age‐matched untrained rats, significant but transient increases were observed in axo‐spinous synapse density and synapse‐to‐neuron ratio 9 h after the start of training, but not at earlier (3 h) or later (24 h) times. These changes at 9 h post‐training were accompanied by transient decreases in both mean synaptic height and area of postsynaptic density. No such changes were observed in an exercise‐matched control group of rats, indicating that the transient synaptic changes in the dentate gyrus are most likely to be specifically related to processes involved in memory formation for the spatial learning task.
Presence of functional vasopressin receptors in spinal ventral horn neurons of young rats: a morphological and electrophysiological study
Authors: Liu X. , Tribollet E. , Ogier R. , Barberis C. , Raggenbass M. 
Published: May 2003

AbstractThe objective of the present work was double. (i) Light microscopic autoradiography was used to determine the distribution of vasopressin and oxytocin binding sites in the spinal cord of rats. (ii) Whole‐cell recordings were performed in lumbar spinal cord slices in order to assess whether these receptors are functional, whether they are located pre‐ or postsynaptically and whether they are present in motoneurons. In newborns, vasopressin binding sites of the V1a type were present in all laminae of the central gray at all segmental levels, whereas oxytocin binding sites were found only in the superficial layers of the dorsal horn. In adults, binding sites for both neuropeptides were also present, but were less dense. The dissociation constants for vasopressin were similar in newborns and adults. Whole‐cell recordings showed that in identified motoneurons vasopressin exerted a direct effect, by inducing a membrane depolarization or by generating a sustained inward current, and an indirect effect, by enhancing glycinergic and GABAergic inhibitory transmission. Vasopressin‐induced facilitation of inhibitory transmission could also be demonstrated in unidentified ventral horn neurons. All these effects were mediated by V1a but not V1b receptors. In some neurons, glycinergic transmission was also facilitated by a selective oxytocin receptor agonist. Our data, together with data obtained previously in brainstem motor nuclei, suggest that vasopressin of hypothalamic origin could play a role in motricity. The neuropeptide could act as a neuromodulator, because it would not directly activate motoneurons, but rather render them more responsive to incoming excitatory inputs. Vasopressin may thus act as a regulator of muscular force.
Tumor necrosis factor receptor type‐1 in sensory neurons contributes to induction of chronic enhancement of inflammatory hyperalgesia in rat
Authors: Parada Carlos A. , Yeh Jenny J. , Joseph Elizabeth K. , Levine Jon D. 
Published: May 2003

AbstractCarrageenan‐induced inflammatory pain lasting hours to days produces a protein kinase C epsilon (PKCɛ)‐dependent ‘primed’ state lasting several weeks, during which time injection of prostaglandin E2 induces hyperalgesia which is markedly enhanced and prolonged compared to PGE2‐induced hyperalgesia in normal ‘unprimed’ rats. In the present study, we demonstrate that while inhibition of prostaglandin synthesis and antagonism of β2‐adrenergic receptors markedly attenuated the hyperalgesia induced by carrageenan, these interventions did not affect hyperalgesic priming. Tumor necrosis factor‐α (rat recombinant; rrTNFα), another mediator of carrageenan‐induced inflammation, alone produced hyperalgesia and priming, which were attenuated and prevented, respectively, by intrathecal administration of antisense to PKCɛ. Inhibition of TNFα with thalidomide or a rat polyclonal anti‐TNFα antibody attenuated carrageenan‐induced hyperalgesia and prevented priming. Intrathecal administration of antisense to tumour necrosis factor receptor type‐1 (TNFR1) reduced the level of TNFR1 transported toward the peripheral terminals of sensory neurons, and attenuated both carrageenan‐ and rrTNFα‐induced priming. Acute hyperalgesia induced by carrageenan or rrTNFα remained intact in animals treated with TNFR1 antisense. Our results demonstrate that the generation of the primed state does not require production of hyperalgesia and that TNFα, which is generated during acute inflammation, can act on sensory neurons to induce hyperalgesic priming by activating neuronal PKCɛ.
A subpopulation of rats show social and sleep–waking changes typical of chronic neuropathic pain following peripheral nerve injury
Authors: Monassi Claudia R. , Bandler Richard , Keay Kevin A. 
Published: May 2003

AbstractNeuropathic conditions for which treatment is sought, the so‐called chronic pain syndrome, are characterized usually by complex behavioural disturbances as well as pain. In this study we evaluated whether social behavioural and sleep disruptions occurred after nerve injury. Before and after chronic constriction of the sciatic nerve, resident–intruder and sleep–wake cycles, as well as mechanical and thermal allodynia/hyperalgesia, were quantified. Sciatic nerve injury in all animals reduced withdrawal thresholds to tactile and thermal (cold) stimuli. Resident–intruder and sleep–waking behaviours were altered in some but not all animals. One group (30%, ‘persistent change’) had enduring reductions in dominant behaviour to an intruder and decreased slow‐wave sleep and increased wakefulness during both light and dark cycles. Another group (25%, ‘recovery’) had a transient reduction in dominant behaviours and decreased slow‐wave sleep and increased wakefulness during only the light cycle. In a third group (45%, ‘no effect’) resident–intruder and sleep–waking behaviours remained normal. Our finding that the degree of ‘pain’ as inferred from the allodynia/hyperalgesia was identical in all animals suggests that the alterations to resident–intruder and sleep–wake cycles were independent of the level of sensory disturbance. An absence of correlation between intensity of sensory disturbances and measures of disability (loss of sleep, familial/social problems) is also characteristic of human neuropathic pain. These data indicate that: (i) in a subpopulation of animals sciatic injury results in two of the major complex behavioural changes which are characteristic of neuropathic pain in humans; (ii) testing only for allodynia and hyperalgesia is not sufficient to detect this subpopulation.
Expression of neuroserpin in the visual cortex of the mouse during the developmental critical period
Authors: Wannier‐Morino Patrizia , Rager Günter , Sonderegger Peter , Grabs Detlev 
Published: May 2003

AbstractThe neuronal serine protease inhibitor neuroserpin is widely expressed in the developing and adult brain. In the neocortex, neuroserpin is displayed particularly during the period of synaptic specification and refinement, indicating a role as modulator of extracellular proteolytic processes. The synaptic connections of the visual system of the mouse are shaped during early postnatal life by an activity‐dependent process. We have studied the expression of the neuronal serine protease inhibitor neuroserpin in the primary visual cortex of mice from birth until the end of the critical period by means of reverse transcription polymerase chain reaction and in situ hybridization. The localization and the level of expression were constant throughout this period. Monocular deprivation with an eyelid sutured induced a decrease in neuroserpin expression in neurons of area 17 after 1 week of deprivation, the decrease being more pronounced on the side contralateral to the closed eye. The expression of neuroserpin in the visual cortex during the critical period and its decrease in parallel to the refinement of synaptic contacts after visual deprivation suggests a regulative role of neuroserpin on these processes.
Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum
Authors: Allen Jeremy P. , Hathway Gareth J. , Clarke Neil J. , Jowett Mike I. , Topps Stephanie , Kendrick Keith M. , Humphrey Patrick P. A. , Wilkinson Lawrence S. , Emson Piers C. 
Published: May 2003

AbstractThe peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7‐transmembrane G protein‐coupled receptors, SSTR1–5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by β‐galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell‐type‐specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2‐null mice were selectively refractory to somatostatin‐induced dopamine and glutamate release. In behavioural tests, Sstr2‐null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam‐walking, a test of fine motor control, Sstr2‐null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.