bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Suicide Ideation and Prior Suicide Attempts of Bipolar Patients as Influences on Caregiver Burden
Authors: Chessick Cheryl A. , Perlick Deborah A. , Miklowitz David J. , Kaczynski Richard , Allen Michael H. , Morris Chad D. , Marangell Lauren B. , STED‐BD Family Experience Collaborative Study Group
Published: September 2007

We examined whether caregivers of bipolar patients reporting current suicidal ideation and/or a history of a suicide attempt reported higher levels of burden and/or poorer health compared to caregivers of patients without these suicidality indices. In a cross‐sectional design, caregivers (N = 480) associated with (a) patients with current suicidal ideation or (b) patients with a positive lifetime history of at least one suicide attempt, reported lower general health scores than caregivers associated with patients with neither of these indices. Parents of patients with at least one lifetime attempt reported more burden secondary to role dysfunction than spouses. Levels of depression in caregivers varied with whether the caregiver was a spouse or a parent, and whether patients had a history of suicide attempts, current suicidal ideation, or both.
Trio Controls the Mature Organization of Neuronal Clusters in the Hindbrain
Authors: Backer Stéphanie , Hidalgo-Sánchez Matías , Offner Nicolas , Portales-Casamar Elodie , Debant Anne , Fort Philippe , Gauthier-Rouvière Cécile , Bloch-Gallego Evelyne
Published: September 2007

During the embryonic development of the hindbrain, movements of neuronal clusters allow the formation of mature “pools”, in particular for inferior olivary (ION) and facial motor (fMN) nuclei. The cellular mechanisms of neuron clustering remain uncharacterized. We report that the absence of the Rho–guanine exchange factor Trio, which can activate both RhoG and Rac1in vivo, prevents the proper formation of ION and fMN subnuclei. Rac1, but not RhoG, appears to be a downstream actor in Trio-induced lamellation. In addition, we report thatCadherin-11is expressed by a subset of neurons through the overall period of ION and fMN parcellations, and defects observed intriomutant mice are located specifically in Cadherin-11-expressing regions. Moreover, endogenous Cadherin-11 is found in a complex with Trio when lamellation occurs. Altogether, those results establish a link between Trio activity, the subsequent Rac1 activation, and neuronal clusters organization, as well as a possible recruitment of the Cadherin-11 adhesive receptor to form a complex with Trio.
Experiential Modification of the Trigeminal Reflex Blink Circuit
Authors: Dauvergne Céline , Evinger Craig
Published: September 2007

To characterize the organization and plasticity of the trigeminal reflex blink circuit, we interacted blink-evoking supraorbital (SO) and infraorbital (IO) nerve stimuli in alert rats. Stimulation of either trigeminal branch produced a short-lasting inhibition followed by a longer-lasting facilitation of blinks evoked by stimulating the other nerve. When IO stimulation evoked a smaller blink than SO stimulation (IO < SO), SO stimulation facilitated subsequent IO-evoked blinks more than IO stimulation facilitated SO-evoked blinks. When IO > SO, IO and SO stimulation exerted equivalent facilitation of subsequent reflex blinks. To investigate whether the blink circuit obeyed rules analogous to those governing the associative and spike timing-dependent plasticity exhibited by individual synapses, we compared the effects of 3600 simultaneous IO and SO pairings, asynchronous IO and SO pairings, or synchronous IO and SO pairings separated by 20 ms on temporal interactions between IO and SO inputs to the blink circuit. Simultaneous pairing of a weak IO and a strong SO strengthened the IO input to the blink circuit, whereas asynchronous pairing weakened the stronger input. When the pairing pattern made an afferent input arrive after blink circuit activity, it weakened that afferent input. Analogous to synaptic modifiability, the results revealed that blink-evoking stimuli acted as a “presynaptic input” and blink circuit activity acted as a “postsynaptic spike.” These mechanisms may create the maladaptive reorganization of trigeminal inputs in diseases such as hemifacial spasm.
Myosin Va Mediates Docking of Secretory Granules at the Plasma Membrane
Authors: Desnos Claire , Huet Sébastien , Fanget Isabelle , Chapuis Catherine , Böttiger Caroline , Racine Victor , Sibarita Jean-Baptiste , Henry Jean-Pierre , Darchen François
Published: September 2007

Myosin Va (MyoVa) is a prime candidate for controlling actin-based organelle motion in neurons and neuroendocrine cells. Its function in secretory granule (SG) trafficking was investigated in enterochromaffin cells by wide-field and total internal reflection fluorescence microscopy. The distribution of endogenous MyoVa partially overlapped with SGs and microtubules. Impairing MyoVa function by means of a truncated construct (MyoVa tail) or RNA interference prevented the formation of SG-rich regions at the cell periphery and reduced SG density in the subplasmalemmal region. Individual SG trajectories were tracked to analyze SG mobility. A wide distribution of their diffusion coefficient,Dxy, was observed. Almost immobile SGs (Dxy< 5 × 10−4μm2· s−1) were considered as docked at the plasma membrane based on two properties: (1) SGs that undergo exocytosis have aDxybelow this threshold value for at least 2 s before fusion; (2) a negative autocorrelation of the vertical motion was found in subtrajectories with aDxybelow the threshold. Using this criterion of docking, we found that the main effect of MyoVa inhibition was to reduce the number of docked granules, leading to reduced secretory responses. Surprisingly, this reduction was not attributable to a decreased transport of SGs toward release sites. In contrast, MyoVa silencing reduced the occurrence of long-lasting, but not short-lasting, docking periods. We thus propose that, despite its known motor activity, MyoVa directly mediates stable attachment of SGs at the plasma membrane.
Auditory Cortical Receptive Fields: Stable Entities with Plastic Abilities
Authors: Elhilali Mounya , Fritz Jonathan B. , Chi Tai-Shih , Shamma Shihab A.
Published: September 2007

To form a reliable, consistent, and accurate representation of the acoustic scene, a reasonable conjecture is that cortical neurons maintain stable receptive fields after an early period of developmental plasticity. However, recent studies suggest that cortical neurons can be modified throughout adulthood and may change their response properties quite rapidly to reflect changing behavioral salience of certain sensory features. Because claims of adaptive receptive field plasticity could be confounded by intrinsic, labile properties of receptive fields themselves, we sought to gauge spontaneous changes in the responses of auditory cortical neurons. In the present study, we examined changes in a series of spectrotemporal receptive fields (STRFs) gathered from single neurons in successive recordings obtained over time scales of 30–120 min in primary auditory cortex (A1) in the quiescent, awake ferret. We used a global analysis of STRF shape based on a large database of A1 receptive fields. By clustering this STRF space in a data-driven manner, STRF sequences could be classified as stable or labile. We found that >73% of A1 neurons exhibited stable receptive field attributes over these time scales. In addition, we found that the extent of intrinsic variation in STRFs during the quiescent state was insignificant compared with behaviorally induced STRF changes observed during performance of spectral auditory tasks. Our results confirm that task-related changes induced by attentional focus on specific acoustic features were indeed confined to behaviorally salient acoustic cues and could be convincingly attributed to learning-induced plasticity when compared with “spontaneous” receptive field variability.
Rapid Homeostatic Plasticity in the Intact Adult Visual System
Authors: Riegle Kenneth C. , Meyer Ronald L.
Published: September 2007

Neurons may possess activity-dependent homeostatic mechanisms that permit them to globally alter synaptic strength as activity varies. We used the retinotectal projection of goldfish to test this idea in the intact adult CNS. We first altered tectal neuron activity by selectively manipulating excitatory input. When excitatory synaptic drive to tectal neurons was eliminated by blocking optic fibers, current evoked at optic synapses increased by 183% within 90 min. With partial activity blockade, the increase in synaptic strength scaled with the magnitude of activity depression. This silence-induced potentiation was also rapidly reversible. Conversely, an increase in optic input was followed by a decrease in evoked synaptic current. When optic drive was not altered and tectal neuronal activity was instead increased or decreased pharmacologically via GABAAreceptors, synaptic strength again changed inversely with activity, indicating that synaptic strength changed in response to neuronal activity and not excitatory drive. Furthermore, altered synaptic strength tended to return ongoing activity to baseline. Changes in synaptic strength could also be detected in heterosynaptic pathways, indicating a global response. Finally, changes in synaptic strength were associated with corresponding changes in ongoing and evoked firing rates, indicating that the responsivity of tectal neurons was altered. Thus, tectal neurons exhibit archetypical homeostasis, one of the first robust examples in the intact adult CNS.
Structural Determinants of Transmission at Large Hippocampal Mossy Fiber Synapses
Authors: Rollenhagen Astrid , Sätzler Kurt , Rodríguez E. Patricia , Jonas Peter , Frotscher Michael , Lübke Joachim H. R.
Published: September 2007

Synapses are the key elements for signal processing and plasticity in the brain. To determine the structural factors underlying the unique functional properties of the hippocampal mossy fiber synapse, the complete quantitative geometry was investigated, using electron microscopy of serial ultrathin sections followed by computer-assisted three-dimensional reconstruction. In particular, parameters relevant for transmitter release and synaptic plasticity were examined. Two membrane specializations were found: active zones (AZs), transmitter release sites, and puncta adherentia, putative adhesion complexes. Individual boutons had, on average, 25 AZs (range, 7–45) that varied in shape and size (mean, 0.1 μm2; range, 0.07–0.17 μm2). The mean distance between individual AZs was 0.45 μm. Mossy fiber boutons and their target structures were mostly ensheathed by astrocytes, but fine glial processes never reached the active zones. Two structural factors are likely to promote synaptic cross talk: the short distance between AZs and the absence of fine glial processes at AZs. Thus, synaptic cross talk may contribute to the efficacy of hippocampal mossy fiber synapses. On average, a bouton contained 20,400 synaptic vesicles; ∼900 vesicles were located within 60 nm from the active zone, ∼4400 between 60 and 200 nm, and the remaining beyond 200 nm, suggesting large readily releasable, recycling, and reserve pools. The organization of the different pools may be a key structural correlate of presynaptic plasticity at this synapse. Thus, the mossy fiber bouton differs fundamentally in structure and function from the calyx of Held and other central synapses.
Cell Surface AMPA Receptors in the Rat Nucleus Accumbens Increase during Cocaine Withdrawal But Internalize after Cocaine Challenge in Association with Altered Activation of Mitogen-Activated Protein Kinases
Authors: Boudreau Amy C. , Reimers Jeremy M. , Milovanovic Michael , Wolf Marina E.
Published: September 2007

Although some studies report increased responsiveness of nucleus accumbens (NAc) AMPA receptors (AMPARs) after withdrawal from repeated cocaine treatment, others report decreased responsiveness after withdrawal plus cocaine challenge. Here we examine this apparent contradiction by quantifying cell surface and intracellular AMPAR subunits in the NAc before and after a challenge injection in behaviorally sensitized rats. Because MAPKs (mitogen-activated protein kinases) regulate AMPAR trafficking and are implicated in addiction, we also evaluated phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Glutamate receptor 1 (GluR1) and GluR2 surface/intracellular (S/I) ratios were increased after 14 d of withdrawal in sensitized rats but were decreased 24 h after challenge with cocaine (which elicited a sensitized locomotor response) or saline (which elicited conditioned locomotion). These findings suggested redistribution of GluR1/2-containing receptors, a possibility supported by immunoprecipitation experiments indicating that most AMPARs in the NAc are GluR1/2 or GluR2/3, with few homomeric GluR1 or GluR1/3 receptors. In sensitized rats, ERK phosphorylation in the NAc increased during withdrawal and normalized after cocaine challenge. JNK phosphorylation also increased after withdrawal, but after cocaine challenge, it was inversely related to GluR1 and GluR2 S/I ratios. After saline challenge, p38 phosphorylation was increased. In summary, surface expression of GluR1/2-containing AMPARs increased in the NAc of sensitized rats, but AMPARs internalized after a single reexposure to cocaine or cocaine-related cues. ERK phosphorylation paralleled AMPAR surface expression. Although JNK results were complex, JNK and p38 may be involved in AMPAR internalization after cocaine or saline challenge, respectively.
Enhanced Hippocampal Long-Term Potentiation and Spatial Learning in Aged 11β-Hydroxysteroid Dehydrogenase Type 1 Knock-Out Mice
Authors: Yau Joyce L. W. , McNair Kara M. , Noble June , Brownstein David , Hibberd Carina , Morton Nik , Mullins John J. , Morris Richard G. M. , Cobb Stuart , Seckl Jonathan R.
Published: September 2007

Glucocorticoids are pivotal in the maintenance of memory and cognitive functions as well as other essential physiological processes including energy metabolism, stress responses, and cell proliferation. Normal aging in both rodents and humans is often characterized by elevated glucocorticoid levels that correlate with hippocampus-dependent memory impairments. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies local intracellular (“intracrine”) glucocorticoid action; in the brain it is highly expressed in the hippocampus. We investigated whether the impact of 11β-HSD1 deficiency in knock-out mice (congenic on C57BL/6J strain) on cognitive function with aging reflects direct CNS or indirect effects of altered peripheral insulin-glucose metabolism. Spatial learning and memory was enhanced in 12 month “middle-aged” and 24 month “aged”11β-HSD1−/−mice compared with age-matched congenic controls. These effects were not caused by alterations in other cognitive (working memory in a spontaneous alternation task) or affective domains (anxiety-related behaviors), to changes in plasma corticosterone or glucose levels, or to altered age-related pathologies in11β-HSD1−/−mice. Young11β-HSD1−/−mice showed significantly increased newborn cell proliferation in the dentate gyrus, but this was not maintained into aging. Long-term potentiation was significantly enhanced in subfield CA1 of hippocampal slices from aged11β-HSD1−/−mice. These data suggest that 11β-HSD1 deficiency enhances synaptic potentiation in the aged hippocampus and this may underlie the better maintenance of learning and memory with aging, which occurs in the absence of increased neurogenesis.
Broad-Spectrum Efficacy across Cognitive Domains by α7 Nicotinic Acetylcholine Receptor Agonism Correlates with Activation of ERK1/2 and CREB Phosphorylation Pathways
Authors: Bitner Robert S. , Bunnelle William H. , Anderson David J. , Briggs Clark A. , Buccafusco Jerry , Curzon Peter , Decker Michael W. , Frost Jennifer M. , Gronlien Jens Halvard , Gubbins Earl , Li Jinhe , Malysz John , Markosyan Stella , Marsh Kennan , Meyer Michael D. , Nikkel Arthur L. , Radek Richard J. , Robb Holly M. , Timmermann Daniel , Sullivan James P. , Gopalakrishnan Murali
Published: September 2007

The α7 nicotinic acetylcholine receptor (nAChR) plays an important role in cognitive processes and may represent a drug target for treating cognitive deficits in neurodegenerative and psychiatric disorders. In the present study, we used a novel α7 nAChR-selective agonist, 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941) to interrogate cognitive efficacy, as well as examine potential cellular mechanisms of cognition. Exhibiting high affinity to native rat (Ki= 10.8 nm) and human (Ki= 16.7 nm) α7 nAChRs, A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. In addition, A-582941 normalized sensory gating deficits induced by the α7 nAChR antagonist methyllycaconitine in rats, and in DBA/2 mice that exhibit a natural sensory gating deficit. Examination of signaling pathways known to be involved in cognitive function revealed that α7 nAChR agonism increased extracellular-signal regulated kinase 1/2 (ERK1/2) phosphorylation in PC12 cells. Furthermore, increases in ERK1/2 and cAMP response element-binding protein (CREB) phosphorylation were observed in mouse cingulate cortex and/or hippocampus after acute A-582941 administration producing plasma concentrations in the range of α7 binding affinities and behavioral efficacious doses. The MEK inhibitor SL327 completely blocked α7 agonist-evoked ERK1/2 phosphorylation. Our results demonstrate that α7 nAChR agonism can lead to broad-spectrum efficacy in animal models at doses that enhance ERK1/2 and CREB phosphorylation/activation and may represent a mechanism that offers potential to improve cognitive deficits associated with neurodegenerative and psychiatric diseases, such as Alzheimer's disease and schizophrenia.
ΔFosB Induction in Orbitofrontal Cortex Mediates Tolerance to Cocaine-Induced Cognitive Dysfunction
Authors: Winstanley Catharine A. , LaPlant Quincey , Theobald David E. H. , Green Thomas A. , Bachtell Ryan K. , Perrotti Linda I. , DiLeone Ralph J. , Russo Scott J. , Garth William J. , Self David W. , Nestler Eric J.
Published: September 2007

Current cocaine users show little evidence of cognitive impairment and may perform better when using cocaine, yet withdrawal from prolonged cocaine use unmasks dramatic cognitive deficits. It has been suggested that such impairments arise in part through drug-induced dysfunction within the orbitofrontal cortex (OFC), yet the neurobiological mechanisms remain unknown. We observed that chronic cocaine self-administration increased expression of the transcription factor ΔFosB within both medial and orbitofrontal regions of the rat prefrontal cortex. However, the increase in OFC ΔFosB levels was more pronounced after self-administered rather than experimenter-administered cocaine, a pattern that was not observed in other regions. We then used rodent tests of attention and decision making to determine whether ΔFosB within the OFC contributes to drug-induced alterations in cognition. Chronic cocaine treatment produced tolerance to the cognitive impairments caused by acute cocaine. Overexpression of a dominant-negative antagonist of ΔFosB, ΔJunD, in the OFC prevented this behavioral adaptation, whereas locally overexpressing ΔFosB mimicked the effects of chronic cocaine. Gene microarray analyses identified potential molecular mechanisms underlying this behavioral change, including an increase in transcription of metabotropic glutamate receptor subunit 5 and GABAAreceptors as well as substance P. Identification of ΔFosB in the OFC as a mediator of tolerance to the effects of cocaine on cognition provides fundamentally new insight into the transcriptional modifications associated with addiction.
Gain Mechanisms for Contextually Guided Visuomotor Transformations
Authors: Brozović Marina , Gail Alexander , Andersen Richard A.
Published: September 2007

A prevailing question in sensorimotor research is the integration of sensory signals with abstract behavioral rules (contexts) and how this results in decisions about motor actions. We used neural network models to study how context-specific visuomotor remapping may depend on the functional connectivity among multiple layers. Networks were trained to perform different rotational visuomotor associations, depending on the stimulus color (a nonspatial context signal). In network I, the context signal was propagated forward through the network (bottom-up), whereas in network II, it was propagated backwards (top-down). During the presentation of the visual cue stimulus, both networks integrate the context with the sensory information via a mechanism similar to the classic gain field. The recurrence in the networks hidden layers allowed a simulation of the multimodal integration over time. Network I learned to perform the proper visuomotor transformations based on a context-modulated memory of the visual cue in its hidden layer activity. In network II, a brief visual response, which was driven by the sensory input, is quickly replaced by a context-modulated motor-goal representation in the hidden layer. This happens because of a dominant feedback signal from the output layer that first conveys context information, and then, after the disappearance of the visual cue, conveys motor goal information. We also show that the origin of the context information is not necessarily closely tied to the top-down feedback. However, we suggest that the predominance of motor-goal representations found in the parietal cortex during context-specific movement planning might be the consequence of strong top-down feedback originating from within the parietal lobe or from the frontal lobe.
Paradoxical Facilitatory Effect of Low-Dose Alcohol Consumption on Memory Mediated by NMDA Receptors
Authors: Kalev-Zylinska Maggie L. , During Matthew J.
Published: September 2007

Epidemiological studies have suggested a negative correlation between alcohol intake and Alzheimer's disease.In vitro, ethanol negatively modulates NMDA receptor function. We hypothesized that chronic moderate alcohol intake leads to improved memory via adaptive responses in the expression of NMDA receptors and downstream signaling. We fed liquid diets containing no, moderate, or high amounts of ethanol to control and matched rats with hippocampal knock-down of the NR1 subunit. Rats with increased hippocampal NR1 expression were also generated to determine whether they had a phenotype similar to that of ethanol-fed animals. We found that moderate ethanol intake improved memory, increased NR1 expression, and changed some aspects of neurotrophin signaling. NR1 knock-down prevented ethanol's facilitatory effects, whereas hippocampal NR1 overexpression mimicked the effect of chronic low-dose ethanol intake on memory. In contrast, high-dose ethanol reduced neurogenesis, inhibited NR2B expression, and impaired visual memory. In conclusion, adaptive changes in hippocampal NMDA receptor expression may contribute to the positive effects of ethanol on cognition.
Off-Line Processing: Reciprocal Interactions between Declarative and Procedural Memories
Authors: Brown Rachel M. , Robertson Edwin M.
Published: September 2007

The acquisition of declarative (i.e., facts) and procedural (i.e., skills) memories may be supported by independent systems. This same organization may exist, after memory acquisition, when memories are processed off-line during consolidation. Alternatively, memory consolidation may be supported by interactive systems. This latter interactive organization predicts interference between declarative and procedural memories. Here, we show that procedural consolidation, expressed as an off-line motor skill improvement, can be blocked by declarative learning over wake, but not over a night of sleep. The extent of the blockade on procedural consolidation was correlated to participants' declarative word recall. Similarly, in another experiment, the reciprocal relationship was found: declarative consolidation was blocked by procedural learning over wake, but not over a night of sleep. The decrease in declarative recall was correlated to participants' procedural learning. These results challenge the concept of fixed independent memory systems; instead, they suggest a dynamic relationship, modulated by when consolidation takes place, allowing at times for a reciprocal interaction between memory systems.
Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo
Authors: Messaoudi Elhoucine , Kanhema Tambudzai , Soulé Jonathan , Tiron Adrian , Dagyte Girstaute , da Silva Bruno , Bramham Clive R.
Published: September 2007

New gene expression is necessary for long-term potentiation (LTP) consolidation, yet roles for specific activity-induced mRNAs have not been defined. Here we probed the dynamic function of activity-induced Arc (activity-regulated cytoskeletal-associated protein)/Arg3.1 (activity-regulated gene 3.1 protein homolog) mRNA using brief, local infusions of antisense (AS) oligodeoxynucleotides at multiple time points during dentate gyrus LTPin vivo. Surprisingly, early Arc synthesis is necessary for early expression of LTP, whereas sustained synthesis is required to generate stably modified synapses. AS application 2 h after LTP induction results in a rapid and permanent reversal of LTP. This reversal is associated with rapid knockdown of upregulated Arc, dephosphorylation of actin depolymerization factor/cofilin, and loss of nascent filamentous actin (F-actin) at synaptic sites. Infusion of the F-actin stabilizing drug jasplakinolide during LTP maintenance blocks the ability of AS to reverse LTP. These results couple activity-induced expression of Arc to expansion of the actin cytoskeleton underlying enduring LTP. Furthermore, Arc synthesis is required for both the induction and consolidation of LTP elicited by local BDNF infusion, thus identifying Arc as a key molecular effector of BDNF in synaptic plasticity.
Attention Improves Population-Level Frequency Tuning in Human Auditory Cortex
Authors: Okamoto Hidehiko , Stracke Henning , Wolters Carsten H. , Schmael Frank , Pantev Christo
Published: September 2007

Attention improves auditory performance in noisy environments by either enhancing the processing of task-relevant stimuli (“gain”), suppressing task-irrelevant information (“sharpening”), or both. In the present study, we investigated the effect of focused auditory attention on the population-level frequency tuning in human auditory cortex by means of magnetoencephalography. Using complex stimuli consisting of a test tone superimposed on different band-eliminated noises during active listening or distracted listening conditions, we observed that focused auditory attention caused not only gain, but also sharpening of frequency tuning in human auditory cortex as reflected by the N1m auditory evoked response. This combination of gain and sharpening in the auditory cortex may contribute to better auditory performance during focused auditory attention.
A Role for Conditioned Ventral Tegmental Glutamate Release in Cocaine Seeking
Authors: You Zhi-Bing , Wang Bin , Zitzman Dawnya , Azari Soraya , Wise Roy A.
Published: September 2007

Initiation of cocaine self-administration in rats was associated with release of glutamate in the ventral tegmental area (VTA). The glutamate release was transient, despite continued cocaine intake. Similar glutamate release was seen in rats earning, for the first time, unexpected saline rather than expected cocaine. VTA glutamate release was not seen in similarly trained rats earning saline instead of cocaine for the 13th time. VTA glutamate release was also seen in similarly trained rats that received yoked rather than earned cocaine injections on test day. VTA glutamate release was not seen in a group of rats that had never earned cocaine but had received yoked injections during the training period. Glutamate release was also not seen in a group of rats that received yoked injections but had no previous experience with cocaine. VTA GABA levels did not fluctuate during any aspect of cocaine seeking. Blockade of VTA glutamate receptors appeared to attenuate the rewarding effects of intravenous cocaine injections and blocked almost completely the conditioned responding normally seen during extinction trials. These findings indicate that VTA glutamate release is a conditioned response dependent on an associative process and is not a simple consequence of previous cocaine exposure. The findings implicate glutamate as at least one of the sources of VTA signals from reward-associated environmental stimuli.
Nicotine Regulates Multiple Synaptic Proteins by Inhibiting Proteasomal Activity
Authors: Rezvani Khosrow , Teng Yanfen , Shim David , De Biasi Mariella
Published: September 2007

Ubiquitination regulates the degradation, membrane trafficking, and transcription of proteins. At mammalian synapses, the ubiquitin–proteasome system (UPS) influences synaptic transmission and plasticity. Nicotine also has the ability to affect synaptic function via mechanisms that remain partially unknown. We found that nicotine, at concentrations achieved by smokers, reduced proteasomal activity, produced accumulation of ubiquitinated synaptic proteins, and increased total protein levels. In particular, a 24 h exposure to nicotine decreased proteasome-dependent degradation of the α7 nicotinic acetylcholine receptor (nAChR) subunit, as indicated by the accumulation of ubiquitinated α7. The same nicotine treatment increased the levels of the AMPA glutamate receptor subunit GluR1, the NMDA receptor subunit NR2A, the metabotropic receptor mGluR1α, the plasticity factor Homer-1A, and the scaffolding postsynaptic density protein PSD-95, whereas the levels of another scaffolding protein, Shank, were reduced. These changes were associated with an inhibition of proteasomal chymotrypsin-like activity by nicotine. The nAChR antagonist mecamylamine was only partially able to block the effects of nicotine on the UPS, indicating that nAChR activation does not completely explain nicotine-induced inhibition of proteasomal catalytic activity. A competition binding assay suggested a direct interaction between nicotine and the 20S proteasome. These results suggest that the UPS might participate in nicotine-dependent synaptic plasticity.
Endothelial-Specific Knockdown of Interleukin-1 (IL-1) Type 1 Receptor Differentially Alters CNS Responses to IL-1 Depending on Its Route of Administration
Authors: Ching San , Zhang Hao , Belevych Natalya , He Lingli , Lai Wenmin , Pu Xin-an , Jaeger Laura B. , Chen Qun , Quan Ning
Published: September 2007

Interleukin-1 (IL-1) has been implicated as a critical mediator of neuroimmune communication. In the brain, the functional receptor for IL-1, type 1 IL-1 receptor (IL-1R1), is localized primarily to the endothelial cells. In this study, we created an endothelial-specific IL-1R1 knockdown model to test the role of endothelial IL-1R1 in mediating the effects of IL-1. Neuronal activation in the hypothalamus was measured by c-fosexpression in the paraventricular nucleus and the ventromedial preoptic area. In addition, two specific sickness symptoms, febrile response and reduction of locomotor activity, were studied. Intracerebroventricular injection of IL-1 induced leukocyte infiltration into the CNS, activation of hypothalamic neurons, fever, and reduced locomotor activity in normal mice. Endothelial-specific knockdown of IL-1R1 abrogated all these responses. Intraperitoneal injection of IL-1 also induced neuronal activation in the hypothalamus, fever, and reduced locomotor activity, without inducing leukocyte infiltration into the brain. Endothelial-specific knockdown of IL-1R1 suppressed intraperitoneal IL-1-induced fever, but not the induction of c-fosin hypothalamus. When IL-1 was given intravenously, endothelial knockdown of IL-1R1 abolished intravenous IL-1-induced CNS activation and the two monitored sickness symptoms. In addition, endothelial-specific knockdown of IL-1R1 blocked the induction of cyclooxygenase-2 expression induced by all three routes of IL-1 administration. These results show that the effects of intravenous and intracerebroventricular IL-1 are mediated by endothelial IL-1R1, whereas the effects of intraperitoneal IL-1 are partially dependent on endothelial IL-1R1.
Progranulin Mediates Caspase-Dependent Cleavage of TAR DNA Binding Protein-43
Authors: Zhang Yong-Jie , Xu Ya-fei , Dickey Chad A. , Buratti Emanuele , Baralle Francisco , Bailey Rachel , Pickering-Brown Stuart , Dickson Dennis , Petrucelli Leonard
Published: September 2007

TAR DNA binding protein-43 (TDP-43) is the pathologic substrate of neuronal and glial inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTDL-U) and in amyotrophic lateral sclerosis (ALS). Mutations in the progranulin gene (PGRN) have been shown to cause familial FTLD-U. The relationship between progranulin and TDP-43 and their respective roles in neurodegeneration is unknown. We report that progranulin mediates proteolytic cleavage of TDP-43 to generate ∼35 and ∼25 kDa species. Suppression ofPGRNexpression with small interfering RNA leads to caspase-dependent accumulation of TDP-43 fragments that can be inhibited with caspase inhibitor treatment. Cells treated with staurosporine also induced caspase-dependent cleavage and redistribution of TDP-43 from its nuclear localization to cytoplasm. Altered cleavage and redistribution of TDP-43 in cell culture models are similar to findings in FTLD-U and ALS. The results suggest that abnormal metabolism of TDP-43 mediated by progranulin may play a pivotal role in neurodegeneration.
Hypersensitivity of the Anesthesia-Induced Comatose Brain
Authors: Kroeger Daniel , Amzica Florin
Published: September 2007

Increasing levels of anesthesia are thought to produce a progressive loss of brain responsiveness to external stimuli. Here, we present the first report of a state window within anesthesia-induced coma, usually associated with an EEG pattern of burst suppression, during which brain excitability is dramatically increased so that even subliminal stimuli elicit bursts of whole-brain activity. We investigated this phenomenonin vivousing intracellular recordings of both neurons and glia, as well as extracellular calcium and EEG recordings. The results indicate that the bursting activity elicited with mechanical microstimulations, but also with auditory and visual stimuli, is dependent on complex mechanisms, including modulation of excitatory (NMDA) components, gap junction transmission, as well as the extracellular calcium concentration. The occurrence of bursting events is associated with a postburst refractory period that underlies the genesis of the alternating burst-suppression pattern. These findings raise the issue of what burst spontaneity during anesthesia-induced coma means and opens new venues for the handling of comatose patients.
Neuronal Activity in the Primary Somatosensory Thalamocortical Loop Is Modulated by Reward Contingency during Tactile Discrimination
Authors: Pantoja Janaina , Ribeiro Sidarta , Wiest Michael , Soares Ernesto , Gervasoni Damien , Lemos Nelson A. M. , Nicolelis Miguel A. L.
Published: September 2007

Delayed-response sensory discrimination is believed to require primary sensory thalamus and cortex for early stimulus identification and higher-order forebrain regions for the late association of stimuli with rewarded motor responses. Here we investigate neuronal responses in the rat primary somatosensory cortex (S1) and ventral posterior medial nucleus of the thalamus (VPM) during a tactile discrimination task that requires animals to associate two different tactile stimuli with two corresponding choices of spatial trajectory to be rewarded. To manipulate reward expectation, neuronal activity observed under regular reward contingency (CR) was compared with neuronal activity recorded during freely rewarded (FR) trials, in which animals obtained reward regardless of their choice of spatial trajectory. Across-trial firing rates of S1 and VPM neurons varied according to the reward contingency of the task. Analysis of neuronal ensemble activity by an artificial neural network showed that stimulus-related information in S1 and VPM increased from stimulus sampling to reward delivery in CR trials but decreased to chance levels when animals performed FR trials, when stimulus discrimination was irrelevant for task execution. Neuronal ensemble activity in VPM was only correlated with task performance during stimulus presentation. In contrast, S1 neuronal activity was highly correlated with task performance long after stimulus removal, a relationship that peaked during the 300 ms that preceded reward delivery. Together, our results indicate that neuronal activity in the primary somatosensory thalamocortical loop is strongly modulated by reward contingency.
Presynaptic Ca2+/Calmodulin-Dependent Protein Kinase II Modulates Neurotransmitter Release by Activating BK Channels atCaenorhabditis elegansNeuromuscular Junction
Authors: Liu Qiang , Chen Bojun , Ge Qian , Wang Zhao-Wen
Published: September 2007

Although Ca2+/calmodulin-dependent protein kinase II (CaMKII) is enriched at the presynaptic nerve terminal, its role in neurotransmitter release is poorly defined. We assessed the function of presynaptic CaMKII in neurotransmitter release and tested the hypothesis that BK channel is a mediator of presynaptic CaMKII function by analyzing miniature and evoked postsynaptic currents at theCaenorhabditis elegansneuromuscular junction. Both loss-of-function (lf) and gain-of-function (gf) ofunc-43, the gene encoding CaMKII, inhibited neurotransmitter release. The inhibitory effect ofunc-43(gf)was reversed by mutation or blockade of the BK channel SLO-1. SLO-1 expressed inXenopusoocytes could be activated by recombinant rat α-CaMKII, and this effect of CaMKII was abolished by mutating a threonine residue (T425) at a consensus CaMKII phosphorylation site in the first RCK (regulator of conductance for K+) domain of the channel. Expression ofslo-1(T425A) in neurons antagonized the inhibitory effect ofunc-43(gf)on neurotransmitter release asslo-1(lf)did. The inhibitory effect ofunc-43(gf)was not reversed byunc-103(lf),dgk-1(lf), oreat-16(lf), which reportedly suppress behavioral phenotypes ofunc-43(gf). These observations suggest that presynaptic CaMKII is a bidirectional modulator of neurotransmitter release, presumably by phosphorylating different molecular targets, and that its negative modulatory effect on the release is mainly mediated by SLO-1 activation.
A tér és a nyelv világa
Authors: Pléh Csaba
Published: September 2007

A modern pszicholingvisztika kísérleti és gyermeknyelvi
adatokat használ a téri nyelvvel kapcsolatban, hogy adatokat nyerjen az
elsőbbség kérdéséről: melyik irányít, a nyelv vagy a téri megismerés a téri
nyelv tagolódásában. A gazdag téri __
Üres allizmus
Authors: Pethő Bertalan
Published: September 2007

Kedélybetegek és szkizofrének ötéves és 21–33 éves katamnesztikus felmérése alkalmával sajátos viselkedésforma
tűnt fel, melyet erőltetettnek hat_
Interakciós szinkronitás hipnózisban. megbízható-e az egészleges megítélés?
Authors: Biró Eszter , Bányai Éva
Published: September 2007

Az interakciós szinkronitásnak hipnózis-interakciókban is
éppoly fontos szerepe lehet a kapcsolat alakulásában, az interakció
szabályozásában, mint éber intera__
Szüléshez társuló pszichiátriai zavarok
Authors: Török Zsuzsa , Szeverényi Péter
Published: September 2007

Közismert tény, hogy a fejlett országokban nagyon gyakoriak
a hangulati élet zavarai,és hogy kialakulásuk szempontjából lényeges kockázati
tényező __
Crosslinking of Guar and Guar Derivatives
Authors: Lei Cuiyue , Clark Peter E.
Published: September 2007

Crosslinking of guar and guar derivatives has played a major role in improving stimulation of oil and gas wells. While crosslinking has been used for a number of years, many facets of crosslinked systems are still not well understood. Part of the problem is that the traditional methods of determining the properties of crosslinked fluids work well for obtaining the data necessary for treatment design, but yield little insight into the nature of the crosslinked system. A good example of this is found in the development of low polymer concentration crosslinked gels. These gels are important because they lower costs and help to minimize formation damage. In this paper, methods for predicting crosslinkability at low concentrations are reported.

The polymer literature is filled with methods for characterizing polymer solutions almost none of which find wide use in the development of crosslinked fracturing fluids. Dawson et al. (2000) first reported that the concentration at which a polymer solution transitions from dilute to semidilute could be used as a method for determining the potential for low concentration crosslinking in guar or guar-derivative solutions. To test this assertion, we have conducted a series of experiments that not only shows that the dilute-semidilute transition concentration is an important indicator for the polymers used in this study, but also presents a framework for exploring the potential of other polymer systems. These experiments show conclusively that low-polymer concentration crosslinking is strongly related to the value of the critical overlap concentration, c*. Both the critical overlap concentration and the critical crosslinking concentration increase in the order guar-3 < CMG < CMHPG < guar < HPG. In addition, we show that the critical crosslinking concentration for the range of polymer-crosslinking systems studied is correlated to the critical overlap concentration (ccc = 1.8(c*)0.77). A strong case is presented for the ability to crosslink at low concentrations is a strong function of the polymer type and a weak function of the crosslinker type.
Assessing the Uncertainty in Reservoir Description and Performance Predictions With the Ensemble Kalman Filter
Authors: Zafari Mohammad , Reynolds Albert C.
Published: September 2007

Recently, the ensemble Kalman filter (EnKF) has gained popularity in atmospheric science for the assimilation of data and the assess ment of uncertainty in forecasts for complex, largescale problems. A handful of papers have discussed reservoir characterization appli cations of the EnKF, which can easily and quickly be coupled with any reservoir simulator. Neither adjoint code nor specific knowledge of simulator numerics is required for implementation of the EnKF. Moreover, data are assimilated (matched) as they become available; a suite of plausible reservoir models (the ensemble, set of ensemble members or suite or realizations) is continuously up dated to honor data without rematching data assimilated previously. Because of these features, the method is far more efficient for history matching dynamic data than automatic history matching based on optimization algorithms. Moreover, the set of realizations provides a way to evaluate the uncertainty in reservoir description and performance predictions.

Here we establish a firm theoretical relation between randomized maximum likelihood and the ensemble Kalman filter. Although we have previously generated reservoir characterization examples where the method worked well, here we also provide examples where the performance of EnKF does not provide a reliable char acterization of uncertainty.
Incorporating 4D Seismic Data in Reservoir Simulation Models Using Ensemble Kalman Filter
Authors: Skjervheim J.-A. , Evensen G. , Aanonsen S. I. , Ruud B. O. , Johansen T. A.
Published: September 2007

A method based on the ensemble Kalman filter (EnKF) for continuous model updating with respect to the combination of production data and 4D seismic data is presented. When the seismic data are given as a difference between two surveys, a combination of the ensemble Kalman filter and the ensemble Kalman smoother has to be applied. Also, special care has to be taken because of the large amount of data assimilated. Still, the method is completely recursive, with little additional cost compared to the traditional EnKF. The model system consists of a commercial reservoir simulator coupled with a rock physics and seismic modeling software. Both static variables (porosity, permeability, and rock physic parameters) and dynamic variables (saturations and pressures) may be updated continuously with time based on the information contained in the assimilated measurements. The method is applied to a synthetic model and a real field case from the North Sea. In both cases, the 4D seismic data are different variations of inverted seismic. For the synthetic case, it is shown that the introduction of seismic data gives a much better estimate of reservoir permeability. For the field case, the introduction of seismic data gives a very different permeability field than using only production data, while retaining the production match.
Taming Complexities of Coupled Geomechanics in Rock Testing: From Assessing Reservoir Compaction to Analyzing Stability of Expandable Sand Screens and Solid Tubulars
Authors: Kanj M. Y. , Abousleiman Y. N.
Published: September 2007

Well geomechanics and "smart" completion designs in many of Saudi Aramco's fields are essential in supporting the company's efforts to apply the extended-reach and MRC well technologies. MRC wells are being aggressively targeted to optimize development economics, enhance recovery, maximize production, minimize differential drawdown across the sand face, reduce sanding potential, and defer water coning. In addition, many unconsolidated sandstone reservoirs require positive sand-control measures. As such, Expandable Sand Screen (ESS) tubulars have seen a recent surge in applicability for completing conventional and MRC wells in sand-prone, troublesome formations. Today, solid expandable tubulars are being tested on a number of wells in a pseudomonodiameter structure. Though attractive, the long-term performance of these tools in the Arabian Reservoir environments is yet to be explored.

This paper simulates the impact of reservoir production and depletion on expandable tubulars and sand-screen completions when the compacting reservoir behaves as a permeable poroelastic medium. A general poroelastic solution model encompassing a multitude of boundary and initial conditions is discussed in this paper. The model simulates the uniaxial (Ko) testing of solid and hollow geomaterial cylinders (Geertsma 2005). Thus, it helps infer about potential problems that might influence the survivability of "expandables" and disrupt the outflow from the well. The proof cases on reservoir and caprocks presented herein are supported with numerical application, experimental validation, and physical interpretation of the coupled poromechanical processes that are reflected in the anisotropic, time-dependent rock responses during testing. The manuscript also demonstrates that this enhanced approach to modeling visualization will ultimately ease the tractability of the pertinent physical phenomena as well as support the model's computational credibility to engineers and experimentalists in the oil and gas industry.