bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances
Authors: Hinterkeuser Stefan , Schröder Wolfgang , Hager Gerhard , Seifert Gerald , Blümcke Ingmar , Elger Christian E , Schramm Johannes , Steinhäuser Christian 
Published: March 2003

AbstractFunctional properties of astrocytes were investigated with the patch‐clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco‐resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin‐sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to ‐130 mV. Comparative recordings were performed in astrocytes from patients with lesion‐associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion‐associated TLE.During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure‐induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity‐dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.
Q‐ and L‐type calcium channels control the development of calbindin phenotype in hippocampal pyramidal neurons in vitro
Authors: Boukhaddaoui Hassan , Sieso Victor , Scamps Frédérique , Vigues Stephan , Roig Anne , Valmier Jean 
Published: March 2003

AbstractCultured immature hippocampal neurons from embryonic 17‐day‐old rats were used to explore activity‐dependent regulation of neuronal phenotype differentiation in the developing hippocampus. The calbindin‐D28k phenotype of the pyramidal neurons appeared during the first 6 days in culture, and was expressed by 12% of the cells on day 6. Daily stimulation with 50 mm KCl during the first 5 days in vitro increased the number of calbindin‐D28k‐positive pyramidal neurons without affecting neuronal survival. This effect was prevented by buffering extracellular Ca2+. Omega‐agatoxin‐IVA‐sensitive Q‐type and nitrendipine‐sensitive L‐type voltage‐gated Ca2+ channels (VGCCs) carried Ca2+ currents and Ca2+ influx in immature pyramidal neurons at somata level. Blockade of these channels inhibited calbindin‐D28k phenotype induced by 50 mm KCl. Conversely, glutamate‐activated Ca2+ channel antagonists did not affect the KCl‐induced calbindin‐D28k phenotype. Chronic blockade of Q‐ and/or L‐type VGCCs downregulated the normal calbindin‐D28k development of immature pyramidal neurons without affecting neuronal survival, the somatic area of pyramidal neurons or the number of GABAergic‐positive (γ‐aminobutyric acid) interneurons. However, at later developmental stages, Q‐type VGCCs lost their ability to control Ca2+ influx at somata level, and both Q‐ and L‐type VGCCs failed to regulate calbindin‐D28k phenotype. These results suggest that Q‐type channels, which have been predominantly associated with neurotransmitter release in adult brain, transiently act in synergy with L‐type VGCCs to direct early neuronal differentiation of hippocampal pyramidal neurons before the establishment of their synaptic circuits.
Gephyrin, a major postsynaptic protein of GABAergic synapses
Authors: Sassoè‐Pognetto Marco , Fritschy Jean‐Marc 
Published: March 2003

Abstractγ‐aminobutyric acid type A (GABAA) receptors are located at the majority of inhibitory synapses in the mammalian brain. However, the mechanisms by which GABAA receptor subunits are targeted to, and clustered in, the postsynaptic membrane are poorly understood. Recent studies have demonstrated that gephyrin, a protein first identified as a component of the glycine receptor (GlyR) complex, is colocalized with several subtypes of GABAA receptors and is involved in the stabilization of postsynaptic GABAA receptor clusters. Thus, gephyrin functions as a clustering protein for major subtypes of inhibitory ion channel receptors.
Spatial and cortical influences exerted on cuneothalamic and thalamocortical neurons of the cat
Authors: Canedo Antonio , Aguilar Juan 
Published: March 2003

AbstractThis work aimed to study the responses of cuneothalamic and thalamocortical cells to electrical stimulation of the body surface in α‐chloralose‐anaesthetized cats. It was found that both classes of cells had a central excitatory receptive field, an edge overlapping the field centre whose stimulation elicited inhibitory–excitatory (cuneothalamic cells) and excitatory–inhibitory (thalamocortical cells) sequences, and a surrounding or peripheral area usually being inhibitory. Manipulating the descending corticofugal activity by removing the fronto‐parietal cortex, electrical stimulation, or by placing picrotoxin or muscimol over the sensorimotor cortex demonstrated that the cortical feedback potentiated effects driven from the field centre and the surround. In particular this potentiated centre‐driven excitation and surround‐driven inhibition, but some of the data points to more complex patterns. The inhibition elicited in cuneothalamic cells from the edge and the surround of the field was faster than the excitation induced from the field centre. Effects at the edge of the field centre included late excitatory responses relayed via the cerebral cortex. There were also direct corticofugal excitatory inputs to the field centre. Excitatory surrounds were occasionally observed, the assumption being that in most cases these were suppressed by the enhanced inhibition driven from the cortex. The data indicate that the cortico‐subcortical feedback contributes not only to enhance the surround antagonism of a centre response but also to increase the time resolution of thalamic and cuneate relay somesthetic neurons.
Synaptic plasticity in the basolateral amygdala in transgenic mice expressing dominant‐negative cAMP response element‐binding protein (CREB) in forebrain
Authors: Rammes G. , Steckler T. , Kresse A. , Schütz G. , Zieglgänsberger W. , Lutz B. 
Published: March 2003

AbstractElectrophysiological and behavioural experiments were performed in transgenic mice expressing a dominant‐negative form of cAMP response element‐binding protein (CREBA133) in the limbic system. In control littermate in vitro slice preparation, tetanizing the lateral amygdala–basolateral amygdala (BLA) pathway with a single train (100 Hz for 1 s) produced short‐term potentiation (STP) in the BLA. Five trains (10‐s interstimulus interval) induced long‐term potentiation (LTP), which was completely blocked by the N‐methyl‐d‐aspartate (NMDA) receptor antagonist d(–)‐2‐amino‐5‐phosphonopentanoic acid (AP5; 50 μm). When GABAergic (γ‐aminobutyric acid) inhibition was blocked by picrotoxin (10 μm), LTP became more pronounced. Low‐frequency stimulation (1 Hz for 15 min) induced either long‐term depression (LTD) or depotentiation. LTD remained unaffected by AP5 (50 μm) or by the L‐ and T‐type Ca2+‐channel blockers nifedipine (20 μm) and Ni2+ (50 μm), but was prevented by picrotoxin (10 μm), indicating a GABAergic link in the expression of LTD in the BLA. When conditioned fear was tested, a mild impairment was seen in one of three transgenic lines only. Although high levels of mRNA encoding CREBA133 lead to downregulation of endogenous CREB, expression of LTP and depotentiation were unaltered in BLA of these transgenic animals. These results could suggest that residual CREB activity was still present or that CREB per se is dispensable. Alternatively, other CREB‐like proteins were able to compensate for impaired CREB function.
The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes after entorhinal cortex lesions in adult rats
Authors: Thon Niklas , Haas Carola A. , Rauch Uwe , Merten Tobias , Fässler Reinhard , Frotscher Michael , Deller Thomas 
Published: March 2003

AbstractThe chondroitin sulphate proteoglycan brevican is one of the most abundant extracellular matrix molecules in the adult rat brain. It is primarily synthesized by astrocytes and is believed to influence astroglial motility during development and under certain pathological conditions. In order to study a potential role of brevican in the glial reaction after brain injury, its expression was analysed following entorhinal cortex lesion in rats (12 h, 1, 2, 4, 10, 14 and 28 days and 6 months post lesion). In situ hybridization and immunohistochemistry were employed to study brevican mRNA and protein, respectively, in the denervated outer molecular layer of the fascia dentata and at the lesion site. In both regions brevican mRNA was upregulated between 1 and 4 days post lesion. The combination of in situ hybridization with immunohistochemistry for glial fibrillary acidic protein demonstrated that many brevican mRNA‐expressing cells are astrocytes. In the denervated zone of the fascia dentata, immunostaining for brevican was increased by 4 days, reached a maximum by 4 weeks and remained detectable up to 6 months post lesion. Electron microscopic immunocytochemistry showed that brevican is a component of the extracellular matrix compartment. At the lesion site a similar time course of brevican upregulation was observed. These data demonstrate that brevican is upregulated in areas of brain damage as well as in areas denervated by a lesion. They suggest a role of brevican in reactive gliosis and are compatible with the hypothesis that brevican is involved in the synaptic reorganization of denervated brain areas.
Role of the peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) and its natural ligand 15‐deoxy‐Δ12,14‐prostaglandin J2in the regulation of microglial functions
Authors: Bernardo Antonietta , Levi Giulio , Minghetti Luisa 
Published: March 2003

AbstractThe peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) is a member of a large group of nuclear receptors controlling the proliferation of peroxisomes that is involved in the downregulation of macrophage functions. Here, we report that PPAR‐γ was constitutively expressed in rat primary microglial cultures and that such expression was downregulated during microglial activation by endotoxin (LPS). The presence of the PPAR‐γ natural ligand 15‐deoxy‐Δ12,14‐prostaglandin J2(15d‐PGJ2) counteracted the repression of PPAR‐γ expression caused by LPS. In microglial cultures stimulated by LPS, interferon‐γ (IFN‐γ) or by their combination, 15d‐PGJ2reduced the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS). The inhibitory effect was dose‐dependent and did not involve an elevation of cyclic AMP, a second messenger known to inhibit NOS expression in microglia. In addition, 15d‐PGJ2down‐regulated other microglial functions, such as tumour necrosis factor‐α (TNF‐α) synthesis and major histocompatibility complex class II (MHC class II) expression. The effects of 15d‐PGJ2occurred, at least in part, through the repression of two important transcription factors, the signal transducer and activator of transcription 1 and the nuclear factor κB, known to mediate IFN‐γ and LPS cell signalling. Our observations suggest that 15d‐PGJ2, the synthesis of which is likely to occur within the brain, could play an important role in preventing brain damage associated with excessive microglial activation.
Glucocorticoid receptor impairment enhances impulsive responding in transgenic mice performing on a simultaneous visual discrimination task
Authors: Steckler Thomas , Sauvage Magdalena , Holsboer Florian 
Published: March 2003

AbstractTransgenic mice with impaired glucocorticoid receptor (GR) function were tested for their ability to learn and perform a series of simultaneous visual discriminations which allowed a dissociation between accuracy of discrimination from those of motivation and behavioural disinhibition. Animals were first trained on an operant five‐choice simultaneous discrimination autoshaping procedure, followed by a continuous reinforcement schedule on that task. Subsequently, the number of choices was limited to two and data were analysed according to the mathematical methods of signal detection theory (SDT). The effects of GR‐antisense expression on accuracy when different rates of responding were required were studied under different fixed ratio response requirements (FR1–FR10). Autoshaping was retarded in transgenic animals and accuracy was impaired in both the five‐choice and the two‐choice discrimination tasks, although transgenic mice showed clear evidence for learning. Under conditions of low response requirements, transgenic mice showed increased response and cognitive biases, but reduced perceptual bias, and a behavioural disinhibition, characterized by a reduction in errors of omission, decreased response latencies and increased number of responses during the inter‐trial interval. Increasing the response requirement improved performance in transgenic animals as reflected by enhanced accuracy. Moreover, transgenics were less susceptible to the deleterious effects of higher response requirements, as indicated by relatively unaffected bias measures in this group, while bias increased in controls. These results indicate that altered performance in GR‐antisense transgenic animals cannot simply be interpreted as a mnemonic deficit, but that altered motivation and enhanced impulsive responding may account for some of these impairments.
Localization and targeting of SCG10 to the trans‐Golgi apparatus and growth cone vesicles
Authors: Lutjens Robert , Igarashi Michihiro , Pellier Veronique , Blasey Horst , Di Paolo Gilbert , Ruchti Evelyne , Pfulg Claudine , Staple Julie K. , Catsicas Stefan , Grenningloh Gabriele 
Published: March 2003

AbstractSCG10 is a membrane‐associated, microtubule‐destabilizing protein of neuronal growth cones. Using immunoelectron microscopy, we show that in the developing cortex of mice, SCG10 is specifically localized to the trans face Golgi complex and apparently associated with vesicular structures in putative growth cones. Consistent with this, subcellular fractionation of rat forebrain extracts demonstrates that the protein is enriched in the fractions containing the Golgi apparatus and growth cone particles. In isolated growth cone particles, SCG10 was found to be particularly concentrated in the growth cone vesicle fraction. To evaluate the molecular determinants of the specific targeting of SCG10 to growth cones, we have transfected PC12 cells and primary neurons in culture with mutant and fusion cDNA constructs. Deletion of the amino‐terminal domain or mutations within this domain that prevented palmitoylation at cysteines 22 and 24 abolished Golgi localization as well as growth cone targeting, suggesting that palmitoylation of the amino‐terminal domain is a necessary signal for Golgi sorting and possibly transport of SCG10 to growth cones. Fusion proteins consisting of the amino‐terminal domain of SCG10 and the cytosolic proteins stathmin or glutathione‐S‐transferase colocalized with a Golgi marker, α‐mannosidase II, and accumulated in growth cones of both axons and dendrites. These results reveal a novel axonal/dendritic growth cone targeting sequence that involves palmitoylation.
No effect of apolipoprotein E on neuronal cell death due to excitotoxic and apoptotic agents in vitro and neonatal hypoxic ischaemia in vivo
Authors: Lendon Corinne L. , Han Byung Hee , Salimi Kayvon , Fagan Anne M. , Behrens Maria I. , Muller Maureen C. , Holtzman David M. 
Published: March 2003

AbstractThe ε4 allele of apolipoprotein E (apoE) is a genetic risk factor for Alzheimer's disease. Studies also suggest that the ε4 allele may be a risk factor for poor outcome following head trauma, brain haemorrhage and ischaemia. The mechanism by which the presence of an apoE ε4 allele and certain brain injuries act to predispose to Alzheimer's disease and poor outcome following brain injury is unknown. We questioned whether poor outcome after brain injury was due to direct modification by apoE protein and its gene variants of susceptibility to glutamate‐mediated excitotoxic injury and apoptosis, mechanisms of cell death which occur following ischaemia and trauma. We investigated the effect of the presence or absence of endogenous murine apoE protein and different apoE isoforms in modification of the survival of murine embryonic cortical neurons exposed to the glutamate agonist, N‐methyl‐ d‐aspartic acid (NMDA) or apoptotic insult by staurosporine, and on the amount of brain injury sustained following a hypoxic‐ischaemic insult in vivo to the brain of neonatal mice transgenically expressing human apoE ε3 or ε4. Our data provide evidence that apoE does not appear to alter neuronal viability following diverse types of acute neuronal insult, e.g. hypoxic‐ischaemic or acute exposure to injurious agents in the models we have examined. This suggests that if apoE does modify the extent of brain damage and recovery after injury, it seems unlikely to be a result of direct or indirect modulation of excitotoxic or apoptotic cell death.
The accuracy of sound duration representation in the human brain determines the accuracy of behavioural perception
Authors: Amenedo Elena , Escera Carles 
Published: March 2003

AbstractIn recent years, the links between neural activity and perception have been an area of interest in cognitive neuroscience. Combined psychophysiological and psychophysical experiments provide a new powerful tool for establishing the relationship between neural activity and perceptual performance. In animals, intracellular recordings combined with psychophysical detection indices have revealed that a particular neuron or set of neurons can play a critical role in the generation of a perceptual event, showing detection functions (referred to as neurometric functions) which are remarkably similar to psychophysical detection functions, or psychometric functions (Parker & Newsome, (1998) Annu. Rev. Neurosci., 21, 227–277). As noninvasive techniques for recording neural activity are now available, studies combining neuroelectric and psychophysical measures in humans are sparse. In the present study, the accuracy of the human brain in detecting differences in sound duration and the subject's ability to perceive the same differences were tested by means of mismatch negativity (MMN) and the distance between the distributions of false alarms and hits (sensitivity index d′), respectively. It was found that the accuracy of the human auditory system to represent sound duration information is related to the duration context in which the sounds are heard, and that these contextual representations determine the accuracy of perception at the behavioural level.
Deficits of spatial and non‐spatial memory and of auditory fear conditioning following anterior thalamic lesions in mice: comparison with chronic alcohol consumption
Authors: Célérier Aurélie , Ognard Raphaël , Decorte Laurence , Beracochea Daniel 
Published: March 2003

AbstractThis study was aimed at determining (i) whether or not bilateral subtotal lesions of the anterior thalamic nuclei (ATH) in rodents produced memory deficits for spatial and/or non‐spatial information and of auditory fear conditioning, and (ii) if these eventual deficits resemble those produced by chronic alcohol consumption (CAC). Working memory was assessed using both spatial (spontaneous alternation) and non‐spatial (temporal alternation) delayed response tasks. Results showed that ATH lesions induced delay‐dependent memory impairments in both spatial and non‐spatial alternation tasks, as well as a decreased level of auditory and background contextual fear conditioning compared with respective controls. CAC did not induce accelerated rate of forgetting in the spatial and non‐spatial tasks, but increased the vulnerability to interference in the spatial task. CAC impaired only background contextual fear conditioning. We conclude that ATH nuclei are involved in the maintenance of information over time, regardless of the nature (spatial vs. non‐spatial) of the information, and play a role in associative processes for both unimodal (the tone) and polymodal (contextual) information. In contrast, ATH dysfunction does not account for the memory disorders induced by the CAC treatment. Our results contribute to showing that the functional overlap between the structures comprising the hippocampo‐mamillo‐thalamic pathway is only partial.
VIP and PACAP potentiation of nicotinic ACh‐evoked currents in rat parasympathetic neurons is mediated by G‐protein activation
Authors: Liu Dong‐Mei , Cuevas Javier , Adams David J. 
Published: March 2003

AbstractThe effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP27 and PACAP38) on isolated parasympathetic neurons of rat intracardiac and submandibular ganglia were examined under voltage clamp using whole‐cell patch‐clamp recording techniques. VIP and PACAP (≤ 10 n m) selectively and reversibly increased the affinity of nicotinic acetylcholine receptor channels (nAChRs) for their agonists resulting in a potentiation of acetylcholine (ACh)‐evoked whole‐cell currents at low agonist concentrations. VIP‐induced potentiation was observed with either ACh or nicotine as the cholinergic agonist. The VIP‐ but not the PACAP‐induced potentiation of ACh‐evoked currents was inhibited by [Ac‐Tyr1, D‐Phe2]‐GRF 1–29, amide (100 nm), a selective antagonist of VPAC1 and VPAC2 receptors; whereas the PACAP38‐ but not the VIP‐induced potentiation was inhibited by 100 nm PACAP6–38, a PAC1 and VPAC2 receptor antagonist. The signal transduction pathway mediating VIP‐ and PACAP‐induced potentiation of nicotinic ACh‐evoked currents involves a pertussis toxin (PTX)‐sensitive G‐protein. Intracellular application of 200 μm GTPγS or GDPβS inhibited VIP‐induced potentiation of ACh‐evoked whole‐cell currents. GTPγS alone potentiated ACh‐ and nicotine‐evoked currents and the magnitude of these currents was not further increased by VIP or PACAP. The G‐protein subtype modulating the neuronal nAChRs was examined by intracellular dialysis with antibodies directed against αo, αi‐1,2, αi‐3 or β G‐protein subunits. Only the anti‐Gαo and anti‐Gβ antibodies significantly inhibited the effect of VIP and PACAP on ACh‐evoked currents. The potentiation of ACh‐evoked currents by VIP and PACAP may be mediated by a membrane‐delimited signal transduction cascade involving the PTX‐sensitive Go protein.