bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐lesion transcommissural growth of olivary climbing fibres creates functional synaptic microzones
Authors: Sugihara Izumi , Lohof Ann M. , Letellier Mathieu , Mariani Jean , Sherrard Rachel M. 
Published: December 2004

AbstractIn the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, postlesion plasticity may generate alternate paths, providing models to investigate reinnervating axon–target interactions. After unilateral transection of the neonatal rat olivocerebellar path, axons from the ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF)‐like arbors on Purkinje cells (PCs). However, the synaptic function and extent of PC reinnervation remain unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and electrophysiological properties of reinnervating olivocerebellar axons were studied, using axonal reconstruction and patch‐clamp PC recording of CF‐induced synaptic currents. Reinnervated PCs displayed normal CF currents, and the frequency of PC reinnervation decreased with increasing laterality. Reinnervating CF arbors were predominantly normal but 6% branched within the molecular layer forming smaller secondary arbors. CFs arose from transcommissural olivary axons, which branched extensively near their target PCs to produce on average 36 CFs, which is six times more than normal. Axons terminating in the hemisphere developed more CFs than those terminating in the vermis. However, the precise parasagittal microzone organization was preserved. Transcommissural axons also branched, although to a lesser extent, to the deep cerebellar nuclei and terminated in a distribution indicative of the olivo‐cortico‐nuclear circuit. These results show that reinnervating olivocerebellar axons are highly plastic in the cerebellum, compensating anatomically and functionally for early postnatal denervation, and that this reparation obeys precise topographic constraints although axonal plasticity is modified by target (PC or deep nuclear neurons) interactions.
A role for dendritic protein synthesis in hippocampal late LTP
Authors: Bradshaw K. D. , Emptage N. J. , Bliss T. V. P. 
Published: December 2004

AbstractThe late temporal component of long‐term potentiation (LTP), a putative neural mechanism for information storage in the brain, is protein synthesis‐dependent, but the site of obligatory protein synthesis is not known. Here we show that when the protein synthesis inhibitor emetine is applied locally to the apical dendritic field of CA1 pyramidal cells in the murine hippocampus, late LTP is impaired at apical but not at basal dendrites, and conversely when emetine is applied locally to basal dendrites, late LTP is impaired only at basal dendrites. Thus, local protein synthesis modulates the expression of tetanically induced late LTP at Schaffer‐commissural synapses on CA1 pyramidal cells.
Protein synthesis in the amygdala, but not the auditory thalamus, is required for consolidation of Pavlovian fear conditioning in rats
Authors: Maren Stephen , Ferrario Carrie R. , Corcoran Kevin A. , Desmond Timothy J. , Frey Kirk A. 
Published: December 2004

AbstractThe amygdala is an essential neural substrate for Pavlovian fear conditioning. Nevertheless, long‐term synaptic plasticity in amygdaloid afferents, such as the auditory thalamus, may contribute to the formation of fear memories. We therefore compared the influence of protein synthesis inhibition in the amygdala and the auditory thalamus on the consolidation of Pavlovian fear conditioning in Long–Evans rats. Rats received three tone‐footshock trials in a novel conditioning chamber. Immediately after fear conditioning, rats were infused intra‐cranially with the protein synthesis inhibitor, anisomycin. Conditional fear to the tone and conditioning context was assessed by measuring freezing behaviour in separate retention tests conducted at least 24 h following conditioning. Post‐training infusion of anisomycin into the amygdala impaired conditional freezing to both the auditory and contextual stimuli associated with footshock. In contrast, intra‐thalamic infusions of anisomycin or a broad‐spectrum protein kinase inhibitor [1‐(5′‐isoquinolinesulphonyl)‐2‐methylpiperazine, H7] did not affect conditional freezing during the retention tests. Pre‐training intra‐thalamic infusion of the NMDA receptor antagonist 2‐amino‐5‐phosphonopentanoic acid (APV), which blocks synaptic transmission in the auditory thalamus, produced a selective deficit in the acquisition of auditory fear conditioning. Autoradiographic assays of cerebral [14C]‐leucine incorporation revealed similar levels of protein synthesis inhibition in the amygdala and thalamus following intra‐cranial anisomycin infusions. These results reveal that the establishment of long‐term fear memories requires protein synthesis in the amygdala, but not the thalamus, after auditory fear conditioning. Forms of synaptic plasticity that depend on protein synthesis, such as long‐term potentiation, are likely candidates for the encoding and long‐term storage of fear memories in the amygdala.
Environmental enrichment during adolescence reverses the effects of prenatal stress on play behaviour and HPA axis reactivity in rats
Authors: Morley‐Fletcher Sara , Rea Monica , Maccari Stefania , Laviola Giovanni 
Published: December 2004

AbstractPrenatal stress (PS) can produce profound and long‐lasting perturbations of individual adaptive capacities, which in turn can result in an increased proneness to behavioural disorders. Indeed, in PS rats there is evidence of impaired social play behaviour, disturbances in a variety of circadian rhythms, enhanced anxiety and increased hypothalamic–pituitary–adrenal (HPA) axis reactivity. This study was designed to experimentally investigate the degree of reversibility of PS‐induced disturbances of social play and HPA reactivity by assessing the effect of the enrichment of the physical environment on PS rats during periadolescence. PS subjects showed a reduced expression of social play behaviour and a prolonged corticosterone secretion in response to restraint stress, but both these effects were markedly reversed following environmental enrichment. Interestingly, the enrichment procedure increased social behaviour but had no effect on corticosterone secretion in nonstressed animals, indicating a differential impact of the postnatal environment as a function of prenatal background. As a whole, results clearly indicate that rats prenatally exposed to stress can benefit during periadolescence from the modulatory effects of an enriched environment. Moreover, they confirm that PS may well represent a suitable animal model for the design and testing of new therapeutic strategies for behavioural disorders produced by early insults.
Functional segregation of plural regions representing cardinal contours in cat primary visual cortex
Authors: Wang Gang 
Published: December 2004

AbstractOur previous data based on an imaging study suggested that, in cat area 17, the representations of cardinal orientations overlap less than the representation of their nearby angles. The purpose of this study was to further investigate the underlying single‐cell properties. Optical imaging was performed first to map the cortical regions corresponding to the four principal contours, the two cardinals and the two obliques. The cortical region activated by a principal orientation but not by the +10° or −10° neighbouring angles, namely the area with optically relative independent orientation selectivity (RIOS), was mapped together with the regions that overlapped with the +10° and/or −10° neighbouring angles (non‐RIOS). Electrode penetrations were targeted to the RIOS and non‐RIOS regions in each of the four orientations. A comparison between the RIOS and the non‐RIOS regions documented a significantly higher percentage of cells with the orientation preference of the cardinal orientations in the cardinal RIOS region than that seen in the other regions. Additionally, the difference in the tuning width of cells between the RIOS and non‐RIOS in the cardinal region was significantly larger than the difference between the RIOS and non‐RIOS in the oblique region. The cells in the cardinal RIOS region were tuned more sharply and the cells in cardinal non‐RIOS region more broadly than the oblique RIOS and/or the non‐RIOS region, which showed no significant difference. These data strongly suggest the existence of functional segregation in the region corresponding to the cardinal contours.
An in vitro and in vivo study of early deficits in associative learning in transgenic mice that over‐express a mutant form of human APP associated with Alzheimer's disease
Authors: Domínguez‐del‐Toro Eduardo , Rodríguez‐Moreno Antonio , Porras‐García Elena , Sánchez‐Campusano Raudel , Blanchard Véronique , Laville Michel , Böhme Georg A. , Benavides Jesús , Delgado‐García José M. 
Published: December 2004

AbstractTransgenic mice over‐expressing a mutated form of the human amyloid precursor protein (APP, 695 isoform) bearing a mutation associated with Alzheimer's disease (V642I, so‐called London mutation, hereafter APPLd2) and wild‐type controls were studied at age periods (3 and 10 months) prior to the overt development of neuritic amyloid plaques. Both 3‐ and 10‐month‐old APPLd2 mice had reflex eyelid responses like those of controls, but only younger mice were able to acquire a classical conditioning of eyelid responses in a trace paradigm. In vitro studies on hippocampal slices showed that 10‐month‐old APPLd2 mice also presented deficits in paired‐pulse facilitation and long‐term potentiation, but presented a normal synaptic activation of CA1 pyramidal cells by the stimulation of Schaffer collaterals. It is proposed that definite functional changes may appear well in advance of noticeable structural alterations in this animal model of Alzheimer's disease, and that specific learning tasks could have a relevant diagnostic value.
Brain‐derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord
Authors: Slack Sarah E. , Pezet Sophie , McMahon Stephen B. , Thompson Stephen W. N. , Malcangio Marzia 
Published: December 2004

AbstractBrain‐derived neurotrophic factor (BDNF) is involved in the modulation of synaptic transmission in the spinal cord, and several circumstantial lines of evidence suggest that it has the ability to modulate the activity of the NMDA receptor. Here we dissect the signalling mechanisms by which BDNF exerts its neuromodulatory role on the NMDA receptor subunit 1 (NR1). Using a preparation of adult isolated dorsal horn with dorsal roots attached, we found that electrical stimulation of roots induced a concomitant release of BDNF and an increased phosphorylation of NR1, which was partly prevented by the BDNF sequestering molecule, TrkB‐IgG. Using a second approach in vitro, we confirmed that both exogenous glutamate and BDNF (but not other neurotrophins) were able to induce NR1 phosphorylation, in particular at residue Ser‐897. NR1 phosphorylation induced by BDNF was blocked by a TrkB inhibitor, an ERK inhibitor and a PKC inhibitor but not a PKA inhibitor. Activation of PKC using exogenous PMA also led to NR1 phosphorylation. Together these data suggest that BDNF modulates the activity of the receptor by phosphorylation via the kinases ERK and PKC.
Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury
Authors: Pfeifer Katharina , Vroemen Maurice , Blesch Armin , Weidner Norbert 
Published: December 2004

AbstractAdult neural progenitor cells (NPC) are an attractive source for cell transplantation and neural tissue replacement after central nervous system (CNS) injury. Following transplantation of NPC cell suspensions into the acutely injured rat spinal cord, NPC survive; however, they migrate away from the lesion site and are unable to replace the injury‐induced lesion cavity. In the present study we examined (i) whether NPC can be retained within the lesion site after co‐transplantation with primary fibroblasts, and (ii) whether NPC promote axonal regeneration following spinal cord injury. Co‐cultivation of NPC with fibroblasts demonstrated that NPC adhere to fibroblasts and the extracellular matrix produced by fibroblasts. In the presence of fibroblasts, the differentiation pattern of co‐cultivated NPC was shifted towards glial differentiation. Three weeks after transplantation of adult spinal‐cord‐derived NPC with primary fibroblasts as mixed cell suspensions into the acutely injured cervical spinal cord in adult rats, the lesion cavity was completely replaced. NPC survived throughout the graft and differentiated exclusively into glial cells. Quantification of neurofilament‐labeled axons and anterogradely labeled corticospinal axons indicated that NPC co‐grafted with fibroblasts significantly enhanced axonal regeneration. Both neurofilament‐labeled axons and corticospinal axons aligned longitudinally along GFAP‐expressing NPC‐derived cells, which displayed a bipolar morphology reminiscent of immature astroglia. Thus, grafted astroglial differentiated NPC promote axon regrowth following spinal cord injury by means of cellular guidance.
Importance of NO/cGMP signalling via cGMP‐dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol
Authors: Werner Claudia , Raivich Gennadij , Cowen Michael , Strekalova Tatyana , Sillaber Inge , Buters Jeroen T. , Spanagel Rainer , Hofmann Franz 
Published: December 2004

AbstractCyclic GMP is a second messenger for nitric oxide (NO) that acts as a mediator for many different physiological functions. The cGMP‐dependent protein kinases (cGKs) mediate cellular signalling induced by NO and cGMP. Here, we explored the localization of cGMP‐dependent protein kinase type II (cGKII) in the mouse brain. In situ hybridization revealed high levels of cGKII mRNA in cerebral cortex, thalamic nuclei, hypothalamic nuclei, and in several basal forebrain regions including medial septum, striatum and amygdala. The close link to NO and the distribution pattern of cGKII suggested that this enzyme might be involved in emotional reactions and responses to drugs of abuse. Therefore, cGKII knockout animals (cGKII–/–) were compared with littermate controls in behavioural tests (i) for emotion‐linked and (ii) for acute and chronic ethanol responses. Deletion of cGKII did not influence aggressive behaviour but led to enhanced anxiety‐like behaviour. In terms of acute responses to ethanol, cGKII–/– mice were hyposensitive to hypnotic doses of ethanol as measured by the loss of righting reflex, without an alteration in their blood alcohol elimination. In a two‐bottle free choice test, cGKII–/– mice showed elevated alcohol consumption. No taste differences to sweet solutions were observed compared to control animals. In summary, our data show that cGKII activity modulates anxiety‐like behaviour and neurobehavioural effects of alcohol.
Coexistence of competitors in metacommunities due to spatial variation in resource growth rates; does R * predict the outcome of competition?
Authors: Abrams Peter A. , Wilson William G. 
Published: December 2004

AbstractSimple mathematical models are used to investigate the coexistence of two consumers using a single limiting resource that is distributed over distinct patches, and that has unequal growth rates in the different patches. Relatively low movement rates or high demographic rates of an inefficient resource exploiter allow it to coexist at a stable equilibrium with a more efficient species whose ratio of movement to demographic rates is lower. The range of conditions allowing coexistence depends on the between‐patch heterogeneity in resource growth rates, but this range can be quite broad. The between‐patch movement of the more efficient consumer turns patches with high resource growth rates into sources, while low‐growth‐rate patches effectively become sinks. A less efficient species can coexist with or even exclude the more efficient species from the global environment if it is better able to bias its spatial distribution towards the source patches. This can be accomplished with density independent dispersal if the less efficient species has a lower ratio of per capita between‐patch movement rate to demographic rates. Conditions that maximize the range of efficiencies allowing coexistence of two species are: a relatively high level of heterogeneity in resource growth conditions; high dispersal (or low demographic rates) of the superior competitor; and low dispersal (or high demographic rates) of the inferior competitor. Global exclusion of the more efficient competitor requires that the inferior competitor have sufficient movement to also produce a source‐sink environment.
Characterization of a new solvent‐responsive gene locus in Pseudomonas putida F1 and its functionalization as a versatile biosensor
Authors: Phoenix P. , Keane A. , Patel A. , Bergeron H. , Ghoshal S. , Lau P. C. K. 
Published: December 2004

SummaryA new gene cluster, designated sepABC and a divergently transcribed sepR, was found downstream of the two‐component todST phosphorelay system that regulates toluene degradation (the tod pathway) in Pseudomonas putida F1 (PpF1). The deduced amino acid sequences encoded by sepABC show a high homology to bacterial proteins known to be involved in solvent efflux or multidrug pumps. SepA, SepB and SepC are referred to be periplasmic, inner membrane and outer membrane efflux proteins respectively. Effects on growth of various PpF1 mutants compared to that of the wild type in the presence of toluene indicated a possible protective role of the solvent efflux system in a solvent‐stressed environment. Growth tests with the complemented mutants confirmed the involvement of the Sep proteins in conferring solvent tolerance. The sepR gene encodes a 260‐residue polypeptide that is a member of the E. coli IclR repressor protein family. The repressor role of SepR was established by conducting tests with a sep‐lacZ transcriptional fusion in Escherichia coli and PpF1, expression of SepR as a maltose‐binding fusion protein in a DNA binding assay, and mRNA analysis. Southern hybridization experiments and analysis of the P. putida KT2440 genome sequence indicated that sepR is a relatively rare commodity compared to homologues of the sepABC genes. We developed a whole‐cell bioluminescent biosensor, PpF1G4, which contains a chromosomally based sep‐lux transcriptional fusion. The biosensor showed significant induction of the sepABC genes by a wide variety of aromatic molecules, including benzene, toluene, ethylbenzene, and all three isomers of xylene (BTEX), naphthalene, and complex mixtures of aliphatic and aromatic hydrocarbons. PpF1G4 represents a second‐generation biosensor that is not based on a catabolic promoter but is nonetheless inducible by aromatic pollutants and moreover functional under nutrient‐rich conditions.
Heavy metal tolerance and metal homeostasis in Pseudomonas putida as revealed by complete genome analysis
Authors: Cánovas David , Cases Ildefonso , De Lorenzo Víctor 
Published: December 2004

SummaryThe genome of Pseudomonas putida KT2440 encodes an unexpected capacity to tolerate heavy metals and metalloids. The availability of the complete chromosomal sequence allowed the categorization of 61 open reading frames likely to be involved in metal tolerance or homeostasis, plus seven more possibly involved in metal resistance mechanisms. Some systems appeared to be duplicated. These might perform redundant functions or be involved in tolerance to different metals. In total, P. putida was found to bear two systems for arsenic (arsRBCH), one for chromate (chrA), four to six systems for divalent cations (two cadA and two to four czc chemiosmotic antiporters), two systems for monovalent cations: pacS, cusCBA (plus one cryptic silP gene containing a frameshift mutation), two operons for Cu chelation (copAB), one metallothionein for metal(loid) binding, one system for Te/Se methylation (tpmT) and four ABC transporters for the uptake of essential Zn, Mn, Mo and Ni (one nikABCDE, two znuACB and one mobABC). Some of the metal‐related clusters are located in gene islands with atypical genome signatures. The predicted capacity of P. putida to endure exposure to heavy metals is discussed from an evolutionary perspective.
Proteome reference map of Pseudomonas putida strain KT2440 for genome expression profiling: distinct responses of KT2440 and Pseudomonas aeruginosa strain PAO1 to iron deprivation and a new form of superoxide dismutase
Authors: Heim S. , Ferrer M. , Heuer H. , Regenhardt D. , Nimtz M. , Timmis K. N. 
Published: December 2004

SummaryThe genome sequence of Pseudomonas putida strain KT2440, a nutritionally versatile, saprophytic and plant root‐colonizing Gram‐negative soil bacterium, was recently determined by K. E. Nelson et al. (2002, Environ Microbiol 4: 799–808). Here, we present a two‐dimensional gel protein reference map of KT2440 cells grown in mineral salts medium with glucose as carbon source. Proteins were identified by matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) analysis, in conjunction with an in‐house database developed from the genome sequence of KT2440, and ≈  200 two‐dimensional gel spots were assigned. The map was used to assess the genomic response of KT2440 to iron limitation stress and to compare this response with that of the closely related facultative human pathogen Pseudomonas aeruginosa strain PAO1. The synthesis of about 25 proteins was affected in both strains, including four prominent upregulated ferric uptake regulator (Fur) protein‐dependent proteins, but there were also striking differences in their proteome responses, for example in the expression of superoxide dismutases (Sod), which may indicate important roles of iron‐responsive functions in the adaptation of these two bacteria to different lifestyles. The Sod enzyme of KT2440 was shown to be a novel heterodimer of the SodA and SodB polypeptides.
Microcolonies, quorum sensing and cytotoxicity determine the survival of Pseudomonas aeruginosa biofilms exposed to protozoan grazing
Authors: Matz Carsten , Bergfeld Tanja , Rice Scott A. , Kjelleberg Staffan 
Published: December 2004

SummaryThis study was based on the hypothesis that biofilms of the opportunistic pathogen Pseudomonas aeruginosa are successfully adapted to situations of protozoan grazing. We tested P. aeruginosa wild type and strains that were genetically altered, in structural and regulatory features of biofilm development, in response to the common surface‐feeding flagellate Rhynchomonas nasuta. Early biofilms of the wild type showed the formation of grazing resistant microcolonies in the presence of the flagellate, whereas biofilms without the predator were undifferentiated. Grazing on biofilms of quorum sensing mutants (lasR and rhlR/lasR) also resulted in the formation of microcolonies, however, in lower numbers and size compared to the wild type. Considerably fewer microcolonies than the wild type were formed by mutant cells lacking type IV pili, whereas no microcolonies were formed by flagella‐deficient cells. The alginate‐overproducing strain PDO300 developed larger microcolonies in response to grazing. These observations suggest a role of quorum sensing in early biofilms and involvement of flagella, type IV pili, and alginate in microcolony formation in the presence of grazing. More mature biofilms of the wild type exhibited acute toxicity to the flagellate R. nasuta. Rapid growth of the flagellate on rhlR/lasR mutant biofilms indicated a key role of quorum sensing in the upregulation of lethal factors and in grazing protection of late biofilms. Both the formation of microcolonies and the production of toxins are effective mechanisms that may allow P. aeruginosa biofilms to resist protozoan grazing and to persist in the environment.