bluuebunny/crossref_metadata_2025 huggingface dataset:
West Nile Flavivirus Polioencephalomyelitis in a Harbor Seal (Phoca vitulina)
Authors: Piero F. Del , Stremme D. W. , Habecker P. L. , Cantile C.
Published: January 2006

A 12-year-old male harbor seal presented with progressive signs of neurologic dysfunction including head tremors, muzzle twitching, clonic spasms, and weakness. Lesions included polioenceph-alomyelitis with glial nodules, spheroids, neuronophagia, ring hemorrhages, and a few neutrophils. Neurons, fibers, and glial nodules were multifocally colonized with intracytoplasmic West Nile flavivirus antigens that were demonstrated using indirect immunohistochemical analysis. Flavivirus on cultured cells also was isolated and was identified by use of monoclonal antibodies and reverse transcriptase-polymerase chain reaction analysis. Clinical signs of disease and lesion morphology and distribution were similar to those of equine West Nile virus infection. Similar to horses, alpacas, humans, dogs, and reptiles, seals can be dead-end hosts of West Nile virus.
Disseminate Cryptococcosis in a Guenon (Cercopithecus ascanius)
Authors: Helke K. L. , Denver M. C. , Bronson E. , Mankowski J. L.
Published: January 2006

A 23-year-old captive-bred red-tailed guenon ( Cercopithecus ascanius) with a brief history of inappetence, lethargy, and seizures was submitted for necropsy. On postmortem examination, multiple cryptococcomas were identified in brain and heart. Cryptococcus neoformans organisms were also identified microscopically in kidney, eye, and pancreas. Fungal yeast formed rare pseudohyphae. The histologic diagnosis of cryptococcosis was confirmed by a positive test for C. neoformans antigen in a serum sample. Immunohistochemical staining confirmed that macrophages were the principal inflammatory cell in brain lesions and often contained phagocytosed yeast. As disseminate cryptococcosis is often associated with immune suppression, serology and immunohistochemical staining for simian immunodeficiency virus were performed but showed no evidence of SIV infection.
Sodium Currents Activate without a Hodgkin and Huxley-Type Delay in Central Mammalian Neurons
Authors: Baranauskas Gytis , Martina Marco
Published: January 2006

Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. The results show that, within the tested voltage range from -55 to -35 mV, in all of these neurons, the activation time course of the current could be fit, after a brief delay, with a monoexponential function. The duration of delay from the start of the voltage command to the start of the extrapolated monoexponential fit was much smaller than predicted by the HH model. For example, in prefrontal cortex pyramidal neurons, at -46 mV and 12°C, the observed average delay was 140 μs versus the 740 μs predicted by the two-gate HH model and the 1180 μs predicted by the three-gate HH model. These results can be explained by a model with two closed states and one open state. In this model, the transition between two closed states is approximately five times faster than the transition between the second closed state and the open state. This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model.
Peptidomics of a Single Identified Neuron Reveals Diversity of Multiple Neuropeptides with Convergent Actions on Cellular Excitability
Authors: Jiménez Connie R. , Spijker Sabine , de Schipper Simone , Lodder Johannes C. , Janse Cornelis Kees , Geraerts Wijnand P. M. , van Minnen Jan , Syed Naweed I. , Burlingame Alma L. , Smit August B. , Li KaWan
Published: January 2006

In contrast to classical transmitters, the detailed structures and cellular and synaptic actions of neuropeptides are less well described. Peptide mass profiling of single identified neurons of the molluscLymnaea stagnalisindicated the presence of 17 abundant neuropeptides in the cardiorespiratory neuron, visceral dorsal 1 (VD1), and a subset of 14 peptides in its electrically coupled counterpart, right parietal dorsal 2. Altogether, based on this and previous work, we showed that the high number of peptides arises from the expression and processing of four distinct peptide precursor proteins, including a novel one. Second, we established a variety of posttranslational modifications of the generated peptides, including phosphorylation, disulphide linkage, glycosylation, hydroxylation, N-terminal pyroglutamylation, and C-terminal amidation. Specific synapses between VD1 and its muscle targets were formed, and their synaptic physiology was investigated. Whole-cell voltage-clamp analysis of dissociated heart muscle cells revealed, as tested for a selection of representative family members and their modifications, that the peptides of VD1 exhibit convergent activation of a high-voltage-activated Ca current. Moreover, the differentially glycosylated and hydroxylated α2 peptides were more potent than the unmodified α2 peptide in enhancing these currents. Together, this study is the first to demonstrate that single neurons exhibit such a complex pattern of peptide gene expression, precursor processing, and differential peptide modifications along with a remarkable degree of convergence of neuromodulatory actions. This study thus underscores the importance of a detailed mass spectrometric analysis of neuronal peptide content and peptide modifications related to neuromodulatory function.
Calpain-Regulated p35/cdk5 Plays a Central Role in Dopaminergic Neuron Death through Modulation of the Transcription Factor Myocyte Enhancer Factor 2
Authors: Smith Patrice D. , Mount Matthew P. , Shree Raj , Callaghan Steve , Slack Ruth S. , Anisman Hymie , Vincent Inez , Wang Xuemin , Mao Zixu , Park David S.
Published: January 2006

The mechanisms underlying dopamine neuron loss in Parkinson's disease (PD) are not clearly defined. Here, we delineate a pathway by which dopaminergic loss induced by 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) is controlledin vivo. We reported previously that calpains play a central required role in dopamine loss after MPTP treatment. Here, we provide evidence that the downstream effector pathway of calpains is through cyclin-dependent kinase 5 (cdk5)-mediated modulation of the transcription factor myocyte enhancer factor 2 (MEF2). We show that MPTP-induced conversion of the cdk5 activator p35 to a pathogenic p25 form is dependent on calpain activityin vivo. In addition, p35 deficiency attenuates MPTP-induced dopamine neuron loss and behavioral outcome. Moreover, MEF2 is phosphorylated on Ser444, an inactivating site, after MPTP treatment. This phosphorylation is dependent on both calpain and p35 activity, consistent with the model that calpain-mediated activation of cdk5 results in phosphorylation of MEF2in vivo. Finally, we provide evidence that MEF2 is critical for dopaminergic loss because “cdk5 phosphorylation site mutant” of MEF2D provides neuroprotection in an MPTP mouse model of PD. Together, these data indicate that calpain-p35-p25/cdk5-mediated inactivation of MEF2 plays a critical role in dopaminergic lossin vivo.
Balanced Excitation and Inhibition Determine Spike Timing during Frequency Adaptation
Authors: Higley Michael J. , Contreras Diego
Published: January 2006

In layer 4 (L4) of the rat barrel cortex, a single whisker deflection evokes a stereotyped sequence of excitation followed by inhibition, hypothesized to result in a narrow temporal window for spike output. However, awake rats sweep their whiskers across objects, activating the cortex at frequencies known to induce short-term depression at both excitatory and inhibitory synapses within L4. Although periodic whisker deflection causes a frequency-dependent reduction of the cortical response magnitude, whether this adaptation involves changes in the relative balance of excitation and inhibition and how these changes might impact the proposed narrow window of spike timing in L4 is unknown. Here, we demonstrate for the first time that spike output in L4 is determined precisely by the dynamic interaction of excitatory and inhibitory conductances. Furthermore, we show that periodic whisker deflection results in balanced adaptation of the magnitude and timing of excitatory and inhibitory input to L4 neurons. This balanced adaptation mediates a reduction in spike output while preserving the narrow time window of spike generation, suggesting that L4 circuits are calibrated to maintain relative levels of excitation and inhibition across varying magnitudes of input.
Brain Activity Associated with Expectancy-Enhanced Placebo Analgesia as Measured by Functional Magnetic Resonance Imaging
Authors: Kong Jian , Gollub Randy L. , Rosman Ilana S. , Webb J. Megan , Vangel Mark G. , Kirsch Irving , Kaptchuk Ted J.
Published: January 2006

In this study, a well established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle, to investigate the brain network involved in placebo analgesia. Sixteen subjects completed the experiment. We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo-treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the functional magnetic resonance imaging (fMRI) signal difference between post-treatment and pretreatment during pain application on placebo side from the same difference on control side [e.g., placebo (post – pre) – control (post – pre)], significant differences were observed in the bilateral rostral anterior cingulate cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal gyrus, and left inferior parietal lobule. The simple regression (correlation) analysis between each subject's fMRI signal difference of post-treatment and pretreatment difference on placebo and control side and the corresponding subjective pain rating difference showed that significant negative correlation was observed in the bilateral lateral/orbital prefrontal cortex, rACC, cerebellum, right fusiform, parahippocampus, and pons. These results are different from a previous study that found decreased activity in pain-sensitive regions such as the thalamus, insula, and ACC when comparing the response to noxious stimuli applied to control and placebo cream-treated areas of the skin. Our results suggest that placebo analgesia may be configured through multiple brain pathways and mechanisms.
Modulation by Brain Natriuretic Peptide of GABA Receptors on Rat Retinal ON-Type Bipolar Cells
Authors: Yu Yong-Chun , Cao Li-Hui , Yang Xiong-Li
Published: January 2006

Natriuretic peptides (NPs) may work as neuromodulators through their associated receptors [NP receptors (NPRs)]. By immunocytochemistry, we showed that NPR-A and NPR-B were expressed abundantly on both ON-type and OFF-type bipolar cells (BCs) in rat retina, including the dendrites, somata, and axon terminals. Whole-cell recordings made from isolated ON-type BCs further showed that brain natriuretic peptide (BNP) suppressed GABAAreceptor-, but not GABACreceptor-, mediated currents of the BCs, which was blocked by the NPR-A antagonist anantin. The NPR-C agonist c-ANF [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF4-23-NH2] did not suppress GABAAcurrents. The BNP effect on GABAAcurrents was abolished with preincubation with the pGC-A/B antagonist HS-142-1 but mimicked by application of 8-bromoguanosine-3′,5′-cyclomonophosphate. These results suggest that elevated levels of intracellular cGMP caused by activation of NPR-A may mediate the BNP effect. Internal infusion of the cGMP-dependent protein kinase G (PKG) inhibitor KT5823 essentially blocked the BNP-induced reduction of GABAAcurrents. Moreover, calcium imaging showed that BNP caused a significant elevation of intracellular calcium that could be caused by increased calcium release from intracellular stores by PKG. The BNP effect was blocked by the ryanodine receptor modulators caffeine, ryanodine, and ruthenium red but not by the IP3receptor antagonists heparin and xestospongin-C. Furthermore, the BNP effect was abolished after application of the blocker of endoplasmic reticulum Ca2+-ATPase thapsigargin and greatly reduced by the calmodulin inhibitors W-7 and calmidazolium. We therefore conclude that the increased calcium release from ryanodine-sensitive calcium stores by BNP may be responsible for the BNP-caused GABAAresponse suppression in ON-type BCs through stimulating calmodulin.
Inhibitors of Differentiation and DNA Binding (Ids) Regulate Math1 and Hair Cell Formation during the Development of the Organ of Corti
Authors: Jones Jennifer M. , Montcouquiol Mireille , Dabdoub Alain , Woods Chad , Kelley Matthew W.
Published: January 2006

The basic helix-loop-helix (bHLH) transcription factor Math1 (also called Atoh1) is both necessary and sufficient for hair cell development in the mammalian cochlea (Bermingham et al., 1999; Zheng and Gao, 2000). Previous studies have demonstrated that a dynamic pattern of Math1 expression plays a key role in regulating the number and position of mechanosensory hair cells. However, the factors that regulate the temporal and spatial expression of Math1 within the cochlea are unknown. The bHLH-related inhibitors of differentiation and DNA binding (Id) proteins are known to negatively regulate many bHLH transcription factors, including Math1, in a number of different systems. Therefore, Id proteins are good candidates for regulating Math1 in the cochlea. Results from PCR andin situhybridization indicate thatId1,Id2, andId3are expressed within the cochlear duct in a pattern that is consistent with a role in regulation of hair cell development. In particular, expression ofIdsandMath1overlapped in cochlear progenitor cells before cellular differentiation, but a specific downregulation ofIdexpression was observed in individual cells that differentiated as hair cells. In addition, progenitor cells in which the expression of Ids was maintained during the time period for hair cell differentiation were inhibited from developing as hair cells. These results indicate a key role for Ids in the regulation of expression ofMath1and hair cell differentiation in the developing cochlea.
Impaired Glutamate Transport in a Mouse Model of Tau Pathology in Astrocytes
Authors: Dabir Deepa V. , Robinson Michael B. , Swanson Eric , Zhang Bin , Trojanowski John Q. , Lee Virginia M.-Y. , Forman Mark S.
Published: January 2006

Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of tauopathies. The discovery of microtubule-associated protein tau gene mutations that are pathogenic for a heterogenous group of neurodegenerative disorders, called frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17), directly implicate tau abnormalities in the onset/progression of disease. Although the role of tau pathology in neurons in disease pathogenesis is well accepted, the contribution of glial pathology is essentially unknown. We recently generated a transgenic (Tg) mouse model of tau pathology in astrocytes by expressing the human tau protein under the control of the glial fibrillary acidic protein (GFAP) promoter. Both wild-type and FTDP-17 mutant GFAP/tau Tg animals manifest an age-dependent accumulation of tau inclusions in astrocytes that resembles the pathology observed in human tauopathies. We further demonstrate that both strains of Tg mice manifest compromised motor function that correlates with altered expression of the glial glutamate-aspartate transporter and occurs before the development of tau pathology. Subsequently, the Tg mice manifest additional deficits in neuromuscular strength that correlates with reduced expression of glutamate transporter-1 (GLT-1) and occurs concurrent with tau inclusion pathology. Reduced GLT-1 expression was associated with a progressive decrease in sodium-dependent glutamate transport capacity. Reductions in GLT-1 expression were also observed in corticobasal degeneration, a tauopathy with prominent pathology in astrocytes. Less robust changes were observed in Alzheimer's disease in which neuronal tau pathology predominates. Thus, these Tg mice recapitulate features of astrocytic pathology observed in tauopathies and implicate a role for altered astrocyte function in the pathogenesis of these disorders.
Interaction of the Cytosolic Domains of sorLA/LR11 with the Amyloid Precursor Protein (APP) and β-Secretase β-Site APP-Cleaving Enzyme
Authors: Spoelgen Robert , von Arnim Christine A. F. , Thomas Anne V. , Peltan Ithan D. , Koker Mirjam , Deng Amy , Irizarry Michael C. , Andersen Olav M. , Willnow Thomas E. , Hyman Bradley T.
Published: January 2006

sorLA is a recently identified neuronal receptor for amyloid precursor protein (APP) that is known to interact with APP and affect its intracellular transport and processing. Decreased levels of sorLA in the brain of Alzheimer's disease (AD) patients and elevated levels of amyloid-β peptide (Aβ) in sorLA-deficient mice point to the importance of the receptor in this neurodegenerative disorder. We analyzed APP cleavage in an APP-shedding assay and found that both sorLA and, surprisingly, a sorLA tail construct inhibited APP cleavage in a β-site APP-cleaving enzyme (BACE)-dependent manner. In line with this finding, sorLA and the sorLA tail significantly reduced secreted Aβ levels when BACE was overexpressed, suggesting that sorLA influencesβ-cleavage. To understand the effect of sorLA on APP cleavage by BACE, we analyzed whether sorLA interacts with APP and/or BACE. Because both full-length sorLA and sorLA C-terminal tail constructs were functionally relevant for APP processing, we analyzed sorLA–APP for a potential cytoplasmatic interaction domain. sorLA and C99 coimmunoprecipitated, pointing toward the existence of a new cytoplasmatic interaction site between sorLA and APP. Moreover, sorLA and BACE also coimmunoprecipitate. Thus, sorLA interacts both with BACE and APP and might therefore directly affect BACE–APP complex formation. To test whether sorLA impacts BACE–APP interactions, we used a fluorescence resonance energy transfer assay to evaluate BACE–APP interactions in cells. We discovered that sorLA significantly reduced BACE–APP interactions in Golgi. We postulate that sorLA acts as a trafficking receptor that prevents BACE–APP interactions and hence BACE cleavage of APP.
Head Direction Cell Representations Maintain Internal Coherence during Conflicting Proximal and Distal Cue Rotations: Comparison with Hippocampal Place Cells
Authors: Yoganarasimha D. , Yu Xintian , Knierim James J.
Published: January 2006

Place cells of the hippocampal formation encode a spatial representation of the environment, and the orientation of this representation is apparently governed by the head direction cell system. The representation of a well explored environment by CA1 place cells can be split when there is conflicting information from salient proximal and distal cues, because some place fields rotate to follow the distal cues, whereas others rotate to follow the proximal cues (Knierim, 2002a). In contrast, the CA3 representation is more coherent than CA1, because the place fields in CA3 tend to rotate in the same direction (Lee et al., 2004). The present study tests whether the head direction cell network produces a split representation or remains coherent under these conditions by simultaneously recording both CA1 place cells and head direction cells from the thalamus. In agreement with previous studies, split representations of the environment were observed in ensembles of CA1 place cells in ∼75% of the mismatch sessions, in which some fields followed the counterclockwise rotation of proximal cues and other fields followed the clockwise rotation of distal cues. However, of 225 recording sessions, there was not a single instance of the head direction cell ensembles revealing a split representation of head direction. Instead, in most of the mismatch sessions, the head direction cell tuning curves rotated as an ensemble clockwise (94%) and in a few sessions rotated counterclockwise (6%). The findings support the notion that the head direction cells may be part of an attractor network bound more strongly to distal landmarks than proximal landmarks, even under conditions in which the CA1 place representation loses its coherence.
Electrical Hyperexcitation of Lateral Ventral Pacemaker Neurons Desynchronizes Downstream Circadian Oscillators in the Fly Circadian Circuit and Induces Multiple Behavioral Periods
Authors: Nitabach Michael N. , Wu Ying , Sheeba Vasu , Lemon William C. , Strumbos John , Zelensky Paul K. , White Benjamin H. , Holmes Todd C.
Published: January 2006

Coupling of autonomous cellular oscillators is an essential aspect of circadian clock function but little is known about its circuit requirements. Functional ablation of the pigment-dispersing factor-expressing lateral ventral subset (LNV) ofDrosophilaclock neurons abolishes circadian rhythms of locomotor activity. The hypothesis that LNVs synchronize oscillations in downstream clock neurons was tested by rendering the LNVs hyperexcitable via transgenic expression of a low activation threshold voltage-gated sodium channel. When the LNVs are made hyperexcitable, free-running behavioral rhythms decompose into multiple independent superimposed oscillations and the clock protein oscillations in the dorsal neuron 1 and 2 subgroups of clock neurons are phase-shifted. Thus, regulated electrical activity of the LNVs synchronize multiple oscillators in the fly circadian pacemaker circuit.
Enhanced Long-Term Potentiation-Like Plasticity of the Trigeminal Blink Reflex Circuit in Blepharospasm
Authors: Quartarone Angelo , Sant'Angelo Antonino , Battaglia Fortunato , Bagnato Sergio , Rizzo Vincenzo , Morgante Francesca , Rothwell John C. , Siebner Hartwig R. , Girlanda Paolo
Published: January 2006

Benign essential blepharospasm (BEB) is a focal cranial dystonia affecting eye closure. Here, we tested the hypothesis that BEB is associated with abnormal plasticity of the neuronal circuits mediating reflex blinks. In patients with BEB and healthy age-matched controls, we used the conditioning protocol introduced by Mao and Evinger (2001) to induce long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit. High-frequency trains of electrical stimuli were repeatedly given over the right supraorbital nerve (SO) and timed to coincide with the R2 response elicited by a preceding SO stimulus. High-frequency stimulation (HFS) resulted in a long-lasting and input-specific potentiation of the R2 response in both groups, yet the facilitation of the R2 response was markedly increased in patients relative to controls. Botulinum toxin (BTX) injections in both orbicularis oculi muscles normalized the previously enhanced LTP-like plasticity of the R2 response. The increased responsiveness to HFS provides first-time evidence that LTP-like plasticity is increased in the trigeminal reflex circuit of patients affected by BEB. The results also show that the enhanced modifiability is not fixed in BEB, because BTX injections can transiently restore normal LTP-like plasticity. We propose that an abnormal corneal input induced by excessive blinking exacerbates increased LTP-like plasticity in BEB. BTX treatment removes the latter and restores plasticity toward normal values. Our results support the concept that maladaptive reorganization contributes to the pathophysiology of focal dystonias.
Synaptotagmin IV Does Not Alter Excitatory Fast Synaptic Transmission or Fusion Pore Kinetics in Mammalian CNS Neurons
Authors: Ting Jonathan T. , Kelley Brooke G. , Sullivan Jane M.
Published: January 2006

Synaptotagmin IV (Syt IV) is a brain-specific isoform of the synaptotagmin family, the levels of which are strongly elevated after seizure activity. The dominant hypothesis of Syt IV function states that Syt IV upregulation is a neuroprotective mechanism for reducing neurotransmitter release. To test this hypothesis in mammalian CNS synapses, Syt IV was overexpressed in cultured mouse hippocampal neurons, and acute effects on fast excitatory neurotransmission were assessed. We found neurotransmission unaltered with respect to basal release probability, Ca2+dependence of release, short-term plasticity, and fusion pore kinetics. In contrast, expression of a mutant Syt I with diminished Ca2+affinity (R233Q) reduced release probability and altered the Ca2+dependence of release, thus demonstrating the sensitivity of the system to changes in neurotransmission resulting from changes to the Ca2+sensor. Together, these data refute the dominant model that Syt IV functions as an inhibitor of neurotransmitter release in mammalian neurons.
Neurogenesis in the Caudate Nucleus of the Adult Rabbit
Authors: Luzzati Federico , De Marchis Silvia , Fasolo Aldo , Peretto Paolo
Published: January 2006

Stem cells with the potential to give rise to new neurons reside in different regions of the adult rodents CNS, butin vivoonly the hippocampal dentate gyrus and the subventricular zone-olfactory bulb system are neurogenic under physiological condition. Comparative analyses have shown that vast species differences exist in the way the mammalian brain is organized and in its neurogenic capacity. Accordingly, we have demonstrated recently that, in the adult rabbit brain, striking structural plasticity persists in several cortical and subcortical areas. Here, by using markers for immature and mature neuronal and glial cell types, endogenous and exogenously administered cell-proliferation markers, intraventricular cell tracer injections coupled to confocal analysis, three-dimensional reconstructions, and invitrotissue cultures, we demonstrate the existence of newly formed neurons in the caudate nucleus of normal, untreated, adult rabbit. Our results suggest that neurogenesis in the caudate nucleus is a phenomenon independent from that occurring in the adjacent subventricular zone, mostly attributable to the activity of clusters of proliferating cells located within the parenchyma of this nucleus. These clusters originate chains of neuroblasts that ultimately differentiate into mature neurons, which represent only a small percentage of the total neuronal precursors. These results indicate that striatum of rabbit represents a favorable environment for genesis rather than survival of newly formed neurons.
Parietal Cortex Mediates Voluntary Control of Spatial and Nonspatial Auditory Attention
Authors: Shomstein Sarah , Yantis Steven
Published: January 2006

The human posterior parietal cortex (PPC) is widely believed to subserve visually guided spatial behavior, including the control of visual attention, eye movements, and reaching. To explore the generality of this function, we measured human brain activity using functional magnetic resonance imaging during spatial and nonspatial shifts of auditory attention. Both spatial and nonspatial shifts of auditory attention evoked transient activity in the medial superior parietal cortex. These results reveal that the PPC is not exclusively devoted to visuospatial behavior; similar regions within a dorsomedial subcompartment provide a domain-independent reconfiguration signal for the control of spatial and nonspatial attention in both visual and nonvisual modalities.
GABAergic Signaling at Mossy Fiber Synapses in Neonatal Rat Hippocampus
Authors: Safiulina Victoria F. , Fattorini Giorgia , Conti Fiorenzo , Cherubini Enrico
Published: January 2006

In the adult rat hippocampus, granule cell mossy fibers (MFs) form excitatory glutamatergic synapses with CA3 principal cells and local inhibitory interneurons. However, evidence has been provided that, in young animals and after seizures, the same fibers can release in addition to glutamate GABA. Here we show that, during the first postnatal week, stimulation of granule cells in the dentate gyrus gave rise to monosynaptic GABAA-mediated responses in principal cells and in interneurons. These synapses were indeed made by MFs because they exhibited strong paired-pulse facilitation, high sensitivity to the metabotropic glutamate receptor agonistl-AP-4, and short-term frequency-dependent facilitation. MF responses were potentiated by blocking the plasma membrane GABA transporter GAT-1 with NO-711 or by allosterically modulating GABAAreceptors with flurazepam. Chemical stimulation of granule cell dendrites with glutamate induced barrages of GABAA-mediated postsynaptic currents into target neurons. Furthermore, immunocytochemical experiments demonstrated colocalization of vesicular GABA transporter with vesicular glutamate transporter-1 and zinc transporter 3, suggesting that GABA can be taken up and stored in synaptic vesicles of MF terminals.

Additional fibers releasing both glutamate and GABA into principal cells and interneurons were recruited by increasing the strength of stimulation. Both the GABAergic and the glutamatergic component of synaptic currents occurred with the same latency and were reversibly abolished byl-AP-4, indicating that they originated from the MFs. GABAergic signaling may play a crucial role in tuning hippocampal network during postnatal development. Low-threshold GABA-releasing fibers may undergo elimination, and this may occur when GABA shifts from the depolarizing to the hyperpolarizing direction.
The Kv2.1 C Terminus Can Autonomously Transfer Kv2.1-Like Phosphorylation-Dependent Localization, Voltage-Dependent Gating, and Muscarinic Modulation to Diverse Kv Channels
Authors: Mohapatra Durga P. , Trimmer James S.
Published: January 2006

Modulation of K+channels is widely used to dynamically regulate neuronal membrane excitability. The voltage-gated K+channel Kv2.1 is an abundant delayed rectifier K+(IK) channel expressed at high levels in many types of mammalian central neurons where it regulates diverse aspects of membrane excitability. Neuronal Kv2.1 is constitutively phosphorylated, localized in high-density somatodendritic clusters, and has a relatively depolarized voltage dependence of activation. Here, we show that the clustering and voltage-dependent gating of endogenous Kv2.1 in cultured rat hippocampal neurons are modulated by cholinergic stimulation, a common form of neuromodulation. The properties of neuronal Kv2.1 are recapitulated in recombinant Kv2.1 expressed in human embryonic kidney 293 (HEK293) cells, but not COS-1 cells, because of cell background-specific differences in Kv2.1 phosphorylation. As in neurons, Kv2.1 in HEK293 cells is dynamically regulated by cholinergic stimulation, which leads to Ca2+/calcineurin-dependent dephosphorylation of Kv2.1, dispersion of channel clusters, and hyperpolarizing shifts in the voltage-dependent gating properties of the channel. Immunocytochemical, biochemical, and biophysical analyses of chimeric Kv channels show that the Kv2.1 cytoplasmic C-terminal domain can act as an autonomous domain sufficient to transfer Kv2.1-like clustering, voltage-dependent activation, and cholinergic modulation to diverse Kv channels. These findings provide novel mechanistic insights into cholinergic modulation of ion channels and regulation of the localization and voltage-dependent gating properties of the abundant neuronal Kv2.1 channel by cholinergic and other neuromodulatory stimuli.
Glia as a Therapeutic Target: Selective Suppression of Human Amyloid-β-Induced Upregulation of Brain Proinflammatory Cytokine Production Attenuates Neurodegeneration
Authors: Ranaivo Hantamalala Ralay , Craft Jeffrey M. , Hu Wenhui , Guo Ling , Wing Laura K. , Van Eldik Linda J. , Watterson D. Martin
Published: January 2006

A corollary of the neuroinflammation hypothesis is that selective suppression of neurotoxic products produced by excessive glial activation will result in neuroprotection. We report here that daily oral administration to mice of the brain-penetrant compound 4,6-diphenyl-3-(4-(pyrimidin-2-yl)piperazin-1-yl)pyridazine (MW01-5-188WH), a selective inhibitor of proinflammatory cytokine production by activated glia, suppressed the human amyloid-β (Aβ) 1-42-induced upregulation of interleukin-1β, tumor necrosis factor-α, and S100B in the hippocampus. Suppression of neuroinflammation was accompanied by restoration of hippocampal synaptic dysfunction markers synaptophysin and postsynaptic density-95 back toward control levels. Consistent with the neuropathophysiological improvements, MW01-5-188WH therapy attenuated deficits in Y maze behavior, a hippocampal-linked task. Oral MW01-5-188WH therapy begun 3 weeks after initiation of intracerebroventricular infusion of human Aβ decreased the numbers of activated astrocytes and microglia and the cytokine levels in the hippocampus without modifying amyloid plaque burden or altering peripheral tissue cytokine upregulation in response to anin vivoinflammatory challenge. The results provide a novel integrative chemical biology proof in support of the neuroinflammation hypothesis of disease progression, demonstrate that neurodegeneration can be attenuated independently of plaque modulation by targeting innate brain proinflammatory cytokine responses, and indicate the feasibility of developing efficacious, safe, and selective therapies for neurodegenerative disorders by targeting key glial activation pathways.
The Continuous Wagon Wheel Illusion Is Associated with Changes in Electroencephalogram Power at ∼13 Hz
Authors: VanRullen Rufin , Reddy Leila , Koch Christof
Published: January 2006

Continuously moving objects sometimes appear to spontaneously reverse their motion direction. The mechanisms underlying this bistable phenomenon (the “continuous wagon wheel illusion”) are heavily debated, but one interpretation suggests that motion information is perceived in discrete episodes at a rate between 10 and 15 Hz. Here, we asked observers to report the perceived direction of a continuously rotating wheel while 32-channel electroencephalogram (EEG) was recorded. We then separated periods of perceived true from illusory (reversed) motion and compared the EEG power spectrum under these two perceptually distinct yet physically identical conditions. The only reliable difference was observed ∼13 Hz over centroparietal electrodes, independent of the temporal frequency of the wheel. Thus, it is likely to reflect internal processes rather than purely stimulus-driven activity. EEG power (13 Hz) decreased before the onset of illusory motion and increased before transitions back to real motion. Using this relationship, it was possible to predict above chance, on a trial-by-trial basis, the direction of the upcoming perceptual transition. These data are compatible with the idea that motion perception occurs in snapshots <100 ms in duration.
Alternative Logics in Action: Water Management in the Andes
Authors: Holben Symantha A.
Published: January 2006

Water and Power in Highland Peru: The Cultural Politics of Irrigation and Development. Paul H. Gelles. New Brunswick, NJ: Rutgers University Press, 2000.

Water Rights and Empowerment. Rutgerd Boelens and Paul Hoogendam. eds. The Netherlands: Van Gorcum, 2002.
Kill and Chill: Restructuring Canada's Beef Commodity Chain
Authors: Castellano Monica
Published: January 2006

Kill and Chill: Restructuring Canada's Beef Commodity Chain. Ian McLachlan. Toronto: University of Toronto Press 2002.
The Agricultural Revolution of the 20th Century
Authors: Shuler Philip E.
Published: January 2006

The Agricultural Revolution of the 20th Century. Don Paarlberg and Philip Paarlberg. Ames: Iowa State University Press, 2000.
The New Nigerien Hausa Diaspora in the U.S.: surviving and building community on the margins of the global economy
Authors: YOUNGSTEDT SCOTT M.
Published: January 2006

This paper focuses on new Nigerien Hausa diaspora communities in U.S. cities. The economic and political policies of nation‐states and international financial institutions exacerbate the abject poverty of Niger and impel Hausa to migrate to the U.S. where they work in the shadows of the formal economy or in the globalized informal economy. They rely on fluid, overlapping face‐toface, imagined, and virtual communities to mitigate their marginalized position. Nigerien Hausa are creatively mediating and adapting global technologies of time‐space compression—especially the Internet, telephones, and electronic money transfer services—to benefit and link their already established and newly emergent communities in diaspora. Based on multi‐sited ethnographic evidence, this paper highlights the culturally specific ways that Nigerien Hausa navigate through global constraints and opportunities in their active efforts to survive and support their transnational families and communities, while maintaining dignity and solidarity.
Globalization and African Ethnoscapes: contrasting Nigerien Hausa and Nigerian Igbo migratory orders in the U.S.
Authors: REYNOLDS RACHEL R. , YOUNGSTEDT SCOTT M.
Published: January 2006

This short essay, which is a preface to two full length articles by Reynolds and by Youngstedt, also in this volume, highlights important contrasts between two African migratory orders in cities in the United States, especially by examining economic conditions under which the two communities use global information technologies as tools of community cohesion and formation in diaspora. The central contrast is that Nigerien Hausa experiences rest at the margins of the formal economy or at their engagement within informal economies, while Nigerian Igbo peoples' experiences as brain drain professionals means that they are by nature of their migratory order integrated into the hegemonic core of global capital. Ultimately, our ethnographically‐based evidence poses two queries: how does space‐time compression operate differentially in the creation of new “global” communities, and secondly, how are significant groups of global actors emerging as the various strands of globalizing economies take new root within and across old ethnic and national and religious imaginaries of community?
Academics In Motion: cultural encapsulation and feeling at home
Authors: TANDOGAN ZERRIN G. , INCIRLIOGLU EMINE ONARAN
Published: January 2006

In this article we explore the concept of “home” and transnational experiences among expatriate academics in a multicultural housing complex of a private university in Ankara, Turkey. The international academics employed by the university and the educators working in the International School that is also located on campus constitute a sizeable proportion of the residents in this housing complex. Although on‐campus housing that comes with some degree of cultural encapsulation has considerable advantages for a group of expatriates, it also creates perplexities due to the distant location of the campus from the city center, the limited availability of social contact with the locals, and the “sterility” of the university environment. Based on indepth interviews with a small group of these expatriates, we present the quandaries of cultural encapsulation and feeling at home.
Popular Cartographies: youthful imaginings of the global in the streets of Dar es Salaam, Tanzania
Authors: MOYER EILEEN
Published: January 2006

In post‐socialist Tanzania people rarely articulate economic disparity in terms of class. Instead idioms of space and place are employed to designate differences between the haves and have‐nots. The material presented in this paper was gathered during 1999‐2000 research among a group of poor urban youth struggling to make a living in the streets of the downtown business district of Dares Salaam. This location allows for an exploration of various themes related to labor, power, and the politics of development. This article attempts to unravel some of the complex relationships between contemporary processes of globalization and young peoples' efforts to make meaningful lives for themselves (street youth, Dar es Salaam, globalization, informal labor, NGOs).
Paragons of Lifestyle: gated communities and the politics of space in Bombay
Authors: FALZON MARK‐ANTHONY
Published: January 2006

In Bombay (Mumbai), the global phenomenon of gated residential enclaves is burgeoning. The city has a long history of residential segregation along religious and ethno‐linguistic lines; the new developments are more inward‐looking, however, in that they seek to create private, self‐sufficient living and leisure spaces. This shift is located within the local dynamics of a perceived rise in crime, Bombay's increasing communalism, and the politics of exclusion in the city. It is also a characteristic of urban formations worldwide.
Exclusive Greenery: new gated communities in Cairo
Authors: KUPPINGER PETRA
Published: January 2006

This paper examines the construction and marketing of recent upscale gated communities on the Egyptian capital's desert outskirts. Discussing questions of design and their use in promotional materials, I show how global inventories of architecture and social lifestyles are inserted in concrete local marketing contexts. While some of this marketing and subsequently some communities are successful, I argue that many aspects of projects are flawed in their neglect of local social forms and material demands. Differentiating between projects that imply a certain globalization of the local versus those that represent the localization of the abstractly global, I argue that the latter are more likely to fail. Reviewing a number or recent projects I illustrate how they all address upscale material demands, social sentiments and fear, and centrally promise safe and healthy homes and like‐minded neighbors. Drawing on recent western theoretical debates about the increasing segregation of urban spaces, and the disappearance of public spaces, this paper explores the use and limits of such theorizations for the context of a post‐colonial Middle Eastern metropolis.
Getting Around Town: transportation and the built environment in post‐apartheid South Africa
Authors: CZEGLÉDY ANDRÉ P.
Published: January 2006

With respect to the contemporary built environment, notions of space and place may be constructed, framed and defined by the seemingly transitory varieties of movement as much as by more normative, physical locales of residence, work and recreation that generally receive the greatest anthropological attention. This paper investigates the primacy of private vehicles in the context of suburban South African life by placing it against the backdrop of apartheid era planning policies as well as current, post‐apartheid domestic investment strategies. It considers the cultural significance of various modes of transportation with respect to the ways in which urban development in South Africa—and particularly Johannesburg—is currently being contested through the critical dimensions of physical design, access and mobility that help to underpin contemporary modes of material production and consumption.
The Architecture of Racial Segregation: The Challenges of Preserving the Problematical Past
Authors: Weyeneth Robert R.
Published: January 2006

The article examines racial segregation as a spatial system and proposes a conceptual framework for assessing its significance. It analyzes how the ideology of white supremacy influenced design form in the United States and how Jim Crow architecture appeared on the landscape. For African Americans, the settings for everyday life were not simply the confines of this imposed architecture; the article analyzes responses such as the construction of alternative spaces. The discussion concludes by considering the architecture of segregation from the perspective of historic preservation.
Historic Corbin Park: Preservation Success Story or Study in Challenges?
Authors: Rutherford Janice Williams
Published: January 2006

Platted in 1899, the Corbin Park neighborhood in Spokane, Washington, is the only historic district in the city that is listed on all three historic registers: the National Register of Historic Places, the Washington State list of historic properties, and the Spokane Register of Historic Places. A diminutive enclave of eighty-three homes that surround a small, oval-shaped city park, the district offers a case study of several issues surrounding district designation: in the past, its residents have used preservation as an instrument of exclusion, they have accommodated change as the "patina of place" has modified the district's character, and for several decades, the neighborhood has navigated conflict between preservation advocates and park officials—a paradox created by opposing city policies.
Writing a Life with Isabel Flick: An Exploration in Cross-cultural Collaboration
Authors: Goodall Heather
Published: January 2006

Public historians work with the explosive content of contested histories when they research collaboratively at community level, where class, cultural, and racial divides intersect. The naïve optimism of the 1970s, which held that oral history methodologies would allow a transparent and unmediated path for minority voices to be heard, has been rightly challenged. In Australia, Indigenous historians rejected the underlying racism of much Anglo-authored work, producing a rich flowering of Indigenous-authored narratives as they reclaimed the right to tell their own stories. Yet the realities of "in-real-life" activism and community work continue to be cross-cultural and multi-racial. How then can the narratives of such cross-cultural experience be written? This essay reviews one collaboration, the life story of Isabel Flick, Indigenous activist and educator, as Isabel co-authored it with Heather Goodall, white Australian academic and activist. Drawing on the work of Michael Frisch and Linda Tuhawai Smith, Goodall argues that the tensions in the process opened up many questions, and perhaps suggested some answers, about the dilemmas of doing and retelling cross-cultural work.
Snf1-Dependent and Snf1-Independent Pathways of Constitutive ADH2 Expression in Saccharomyces cerevisiae
Authors: Voronkova Valentina , Kacherovsky Nataly , Tachibana Christine , Yu Diana , Young Elton T
Published: January 2006

The transcription factor Adr1 directly activates the expression of genes encoding enzymes in numerous pathways that are upregulated after the exhaustion of glucose in the yeast Saccharomyces cerevisiae. ADH2, encoding the alcohol dehydrogenase isozyme required for ethanol oxidation, is a highly glucose-repressed, Adr1-dependent gene. Using a genetic screen we isolated >100 mutants in 12 complementation groups that exhibit ADR1-dependent constitutive ADH2 expression on glucose. Temperature-sensitive alleles are present among the new constitutive mutants, indicating that essential genes play a role in ADH2 repression. Among the genes we cloned is MOT1, encoding a repressor that inhibits TBP binding to the promoter, thus linking glucose repression with TBP access to chromatin. Two genes encoding proteins involved in vacuolar function, FAB1 and VPS35, and CDC10, encoding a nonessential septin, were also uncovered in the search, suggesting that vacuolar function and the cytoskeleton have previously unknown roles in regulating gene expression. Constitutive activation of ADH2 expression by Adr1 is SNF1-dependent in a strain with a defective MOT1 gene, whereas deletion of SNF1 did not affect constitutive ADH2 expression in the mutants affecting vacuolar or septin function. Thus, the mutant search revealed previously unknown Snf1-dependent and -independent pathways of ADH2 expression.