bluuebunny/crossref_metadata_2025 huggingface dataset:
Telencephalic Embryonic Subtractive Sequences: A Unique Collection of Neurodevelopmental Genes
Authors: Bulfone Alessandro , Carotenuto Pietro , Faedo Andrea , Aglio Veruska , Garzia Livia , Bello Anna Maria , Basile Andrea , Andrè Alessandra , Cocchia Massimo , Guardiola Ombretta , Ballabio Andrea , Rubenstein John L. R. , Zollo Massimo
Published: August 2005

The vertebrate telencephalon is composed of many architectonically and functionally distinct areas and structures, with billions of neurons that are precisely connected. This complexity is fine-tuned during development by numerous genes. To identify genes involved in the regulation of telencephalic development, a specific subset of differentially expressed genes was characterized. Here, we describe a set of cDNAs encoded by genes preferentially expressed during development of the mouse telencephalon that was identified through a functional genomics approach. Of 832 distinct transcripts found, 223 (27%) are known genes. Of the remaining, 228 (27%) correspond to expressed sequence tags of unknown function, 58 (7%) are homologs or orthologs of known genes, and 323 (39%) correspond to novel rare transcripts, including 48 (14%) new putative noncoding RNAs. As an example of this latter group of novel precursor transcripts of micro-RNAs, telencephalic embryonic subtractive sequence (TESS) 24.E3 was functionally characterized, and one of its targets was identified: the zinc finger transcription factorZFP9. The TESS transcriptome has been annotated, mapped for chromosome loci, and arrayed for its gene expression profiles during neural development and differentiation (in Neuro2a and neural stem cells). Within this collection, 188 genes were also characterized on embryonic and postnatal tissue byin situhybridization, demonstrating that most are specifically expressed in the embryonic CNS. The full information has been organized into a searchable database linked to other genomic resources, allowing easy access to those who are interested in the dissection of the molecular basis of telencephalic development.
Limited Segregation of Different Types of Sound Localization Information among Classes of Units in the Inferior Colliculus
Authors: Chase Steven M. , Young Eric D.
Published: August 2005

The auditory system uses three cues to decode sound location: interaural time differences (ITDs), interaural level differences (ILDs), and spectral notches (SNs). Initial processing of these cues is done in separate brainstem nuclei, with ITDs in the medial superior olive, ILDs in the lateral superior olive, and SNs in the dorsal cochlear nucleus. This work addresses the nature of the convergence of localization information in the central nucleus of the inferior colliculus (ICC). Ramachandran et al. (1999) argued that ICC neurons of types V, I, and O, respectively, receive their predominant inputs from ITD-, ILD-, and SN-sensitive brainstem nuclei, suggesting that these ICC response types should be differentially sensitive to localization cues. Here, single-unit responses to simultaneous manipulation of pairs of localization cues were recorded, and the mutual information between discharge rate and individual cues was quantified. Although rate responses to cue variation were generally consistent with those expected from the hypothesized anatomical connections, the differences in information were not as large as expected. Type I units provide the most information, especially about SNs in the physiologically useful range. Type I and O units provide information about ILDs, even at low frequencies at which actual ILDs are very small. ITD information is provided by a subset of all low-frequency neurons. Type V neurons provide information mainly about ITDs and the average binaural intensity. These results are the first to quantify the relative representation of cues in terms of information and suggest a variety of degrees of cue integration in the ICC.
Glycine Receptors in CNS Neurons as a Target for Nonretrograde Action of Cannabinoids
Authors: Lozovaya Natalia , Yatsenko Natalia , Beketov Andrey , Tsintsadze Timur , Burnashev Nail
Published: August 2005

At many central synapses, endocannabinoids released by postsynaptic cells act retrogradely on presynaptic G-protein-coupled cannabinoid receptors to inhibit neurotransmitter release. Here, we demonstrate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels. In isolated hippocampal pyramidal and Purkinje cerebellar neurons, endogenous cannabinoids anandamide and 2-arachidonylglycerol, applied at physiological concentrations, inhibited the amplitude and altered the kinetics of rise time, desensitization, and deactivation of the glycine-activated current (IGly) in a concentration-dependent manner. These effects of cannabinoids were observed in the presence of cannabinoid CB1/CB3, vanilloid receptor 1 antagonists, and the G-protein inhibitor GDPβS, suggesting a direct action of cannabinoids on GlyRs. The effect of cannabinoids onIGlydesensitization was strongly voltage dependent. We also demonstrate that, in the presence of a GABAAreceptor antagonist, GlyRs may contribute to the generation of seizure-like activity induced by short bursts (seven stimuli) of high-frequency stimulation of inputs to hippocampal CA1 region, because this activity was diminished by selective GlyR antagonists (strychnine and ginkgolides B and J). The GlyR-mediated rhythmic activity was also reduced by cannabinoids (anandamide) in the presence of a CB1 receptor antagonist. These results suggest that the direct inhibition of GlyRs by endocannabinoids can modulate the hippocampal network activity.
Vesicle-Mediated Transport and Release of CCL21 in Endangered Neurons: A Possible Explanation for Microglia Activation Remote from a Primary Lesion
Authors: de Jong Eiko K. , Dijkstra Ineke M. , Hensens Marjolein , Brouwer Nieske , van Amerongen Machteld , Liem Robert S. B. , Boddeke Hendrikus W. G. M. , Biber Knut
Published: August 2005

Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion.
Neuroleptic-Induced Catalepsy: Electrophysiological Mechanisms of Functional Recovery Induced by High-Frequency Stimulation of the Subthalamic Nucleus
Authors: Degos Bertrand , Deniau Jean-Michel , Thierry Anne-Marie , Glowinski Jacques , Pezard Laurent , Maurice Nicolas
Published: August 2005

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) remarkably alleviates motor disorders in parkinsonian patients. The mechanisms by which STN HFS exerts its beneficial effects were investigated in anesthetized rats, using a model of acute interruption of dopaminergic transmission. Combined systemic injections of SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine] and raclopride, antagonists of the D1and D2classes of dopaminergic receptors, respectively, were performed, and the parameters of STN HFS that reversed the neuroleptic-induced catalepsy were determined in freely moving animals. The effects of neuroleptics and the impact of STN HFS applied at parameters alleviating neuroleptic-induced catalepsy were analyzed in the substantia nigra pars reticulata (SNR), a major basal ganglia output structure, by recording the neuronal firing pattern and the responses evoked by cortical stimulation. Neuroleptic injection altered the tonic and regular mode of discharge of SNR neurons, most of them becoming irregular with bursts of spikes and pauses. The inhibitory component of the cortically evoked response, which is attributable to the activation of the direct striatonigral circuit, was decreased, whereas the late excitatory response resulting from the indirect striato-pallido-subthalamo-nigral circuit was reinforced. During STN HFS, the spontaneous firing of SNR cells was either increased or decreased with a global enhancement of the firing rate in the overall population of SNR cells recorded. However, in all of the cases, SNR firing pattern was regularized, and the bias between the trans-striatal and trans-subthalamic circuits was reversed. By these effects, STN HFS restores the functional properties of the circuits by which basal ganglia contribute to motor activity.
Reliability of Signal Transfer at a Tonically Transmitting, Graded Potential Synapse of the Locust Ocellar Pathway
Authors: Simmons Peter J. , de Ruyter van Steveninck Rob
Published: August 2005

We assessed the performance of a synapse that transmits small, sustained, graded potentials between two classes of second-order ocellar “L-neurons” of the locust. We characterized the transmission of both fixed levels of membrane potential and fluctuating signals by recording postsynaptic responses to changes in presynaptic potential. To ensure repeatability between stimuli, we controlled presynaptic signals with a voltage clamp. We found that the synapse introduces noise above the level of background activity in the postsynaptic neuron. By driving the presynaptic neuron with slow-ramp changes in potential, we found that the number of discrete signal levels the synapse transmits is ∼20. It can also transmit ∼20 discrete levels when the presynaptic signal is a graded rebound spike. Synaptic noise level is constant over the operating range of the synapse, which would not be expected if presynaptic potential set the probability for the release of individual quanta of neurotransmitter according to Poisson statistics. Responses to individual quanta of neurotransmission could not be resolved, which is consistent with a synapse that operates with large numbers of vesicles evoking small responses. When challenged with white noise stimuli, the synapse can transmit information at rates up to 450 bits/s, a performance that is sufficient to transmit natural signals about changes in illumination.
Regular Exercise Prolongs Survival in a Type 2 Spinal Muscular Atrophy Model Mouse
Authors: Grondard Clément , Biondi Olivier , Armand Anne-Sophie , Lécolle Sylvie , Gaspera Bruno Della , Pariset Claude , Li Hung , Gallien Claude-Louis , Vidal Pierre-Paul , Chanoine Christophe , Charbonnier Frédéric
Published: August 2005

Several studies indicate that physical exercise is likely to be neuroprotective, even in the case of neuromuscular disease. In the present work, we evaluated the efficiency of running-based training on type 2 spinal muscular atrophy (SMA)-like mice. The model used in this study is an SMN (survival motor neuron)-null mouse carrying one copy of a transgene of humanSMN2. The running-induced benefits sustained the motor function and the life span of the type 2 SMA-like mice by 57.3%. We showed that the extent of neuronal death is reduced in the lumbar anterior horn of the spinal cord of running-trained mice in comparison with untrained animals. Notably, exercise enhanced motoneuron survival. We showed that the running-mediated neuroprotection is related to a change of the alternative splicing pattern of exon 7 in theSMN2gene, leading to increased amounts of exon 7-containing transcripts in the spinal cord of trained mice. In addition, analysis at the level of two muscles from the calf, the slow-twitch soleus and the fast-twitch plantaris, showed an overall conserved muscle phenotype in running-trained animals. These data provide the first evidence for the beneficial effect of exercise in SMA and might lead to important therapeutic developments for human SMA patients.
Differential Dynamic Plasticity of A1 Receptive Fields during Multiple Spectral Tasks
Authors: Fritz Jonathan B. , Elhilali Mounya , Shamma Shihab A.
Published: August 2005

Auditory experience leads to myriad changes in processing in the central auditory system. We recently described task-related plasticity characterized by rapid modulation of spectro-temporal receptive fields (STRFs) in ferret primary auditory cortex (A1) during tone detection. We conjectured that each acoustic task may have its own “signature” STRF changes, dependent on the salient cues that the animal must attend to perform the task. To discover whether other acoustic tasks could elicit changes in STRF shape, we recorded from A1 in ferrets also trained on a frequency discrimination task. Overall, we found a distinct pattern of STRF change, characterized by an expected selective enhancement at target tone frequency but also by an equally selective depression at reference tone frequency. When single-tone detection and frequency discrimination tasks were performed sequentially, neurons responded differentially to identical tones, reflecting distinct predictive values of stimuli in the two behavioral contexts. All results were observed in multiunit as well as single-unit recordings. Our findings provide additional evidence for the presence of adaptive neuronal responses in A1 that can swiftly change to reflect both sensory content and the changing behavioral meaning of incoming acoustic stimuli.
Large-Conductance Calcium-Activated Potassium Channels Facilitate Transmitter Release in Salamander Rod Synapse
Authors: Xu Jian Wei , Slaughter Malcolm M.
Published: August 2005

Large-conductance calcium-activated potassium (BK) channels are colocalized with calcium channels at sites of exocytosis at the presynaptic terminals throughout the nervous system. It is expected that their activation would provide negative feedback to transmitter release, but the opposite is sometimes observed. Attempts to resolve this apparent paradox based on alterations in action potential waveform have been ambiguous. In an alternative approach, we investigated the influence of this channel on neurotransmitter release in a nonspiking neuron, the salamander rod photoreceptors. Surprisingly, the BK channel facilitates calcium-mediated transmitter release from rods. The two presynaptic channels form a positive coupled loop. Calcium influx activates the BK channel current, leading to potassium efflux that increases the calcium current. The normal physiological voltage range of the rod is well matched to the dynamics of this positive loop. When the rod is further depolarized, then the hyperpolarizing BK channel current exceeds its facilitatory effect, causing truncation of transmitter release. Thus, the calcium channel-BK channel linkage performs two functions at the synapse: nonlinear potentiator and safety brake.
Loss ofALS2Function Is Insufficient to Trigger Motor Neuron Degeneration in Knock-Out Mice But Predisposes Neurons to Oxidative Stress
Authors: Cai Huaibin , Lin Xian , Xie Chengsong , Laird Fiona M. , Lai Chen , Wen Hongjin , Chiang Hsueh-Cheng , Shim Hoon , Farah Mohamed H. , Hoke Ahmet , Price Donald L. , Wong Philip C.
Published: August 2005

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is caused by a selective loss of motor neurons in the CNS. Mutations in theALS2gene have been linked to one form of autosomal recessive juvenile onset ALS (ALS2). To investigate the pathogenic mechanisms of ALS2, we generatedALS2knock-out (ALS2-/-) mice. AlthoughALS2-/-mice lacked obvious developmental abnormalities, they exhibited age-dependent deficits in motor coordination and motor learning. Moreover,ALS2-/-mice showed a higher anxiety response in the open-field and elevated plus-maze tasks. Although they failed to recapitulate clinical or neuropathological phenotypes consistent with motor neuron disease by 20 months of age,ALS2-/-mice or primary cultured neurons derived from these mice were more susceptible to oxidative stress compared with wild-type controls. These observations suggest that loss ofALS2function is insufficient to cause major motor deficits or motor neuron degeneration in a mouse model but predisposes neurons to oxidative stress.
Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3
Authors: Zhou Zhiping , Liu Qing , Davis Robin L.
Published: August 2005

Auditory information is conveyed into the CNS via the spiral ganglion neurons, cells that possess distinctive electrophysiological properties that vary according to their cochlear innervation. Neurons from the base of the cochlea fire action potentials with shorter latencies and durations with more rapid accommodation than apical neurons (Adamson et al., 2002b). Interestingly, these features are altered by exposure to brain-derived neurotrophic factor and neurotrophin-3 (NT-3), suggesting that the electrophysiological diversity is not preprogrammed into the neurons but instead results from extrinsic regulation. In support of this, gradients of neurotrophins exist in the cochlea that could account for the apex- base differences in firing. To understand the determinants of spiral ganglion function, we characterized the NT-3 concentration dependence and mode of action on spiral ganglion neurons. Whole-cell current-clamp recordings were made from mouse basal spiral ganglion neurons (postnatal day 5) exposed to different concentrations of NT-3 for 3 din vitro. Measurements of accommodation, latency, onset time course, and action potential latency revealed a nonmonotonic dependence on NT-3 concentration, with a peak effect occurring at 10 ng/ml. Addition of NT-3 at different time points showed that neurotrophin exposure altered the firing features of existing neurons rather than supporting differential survival. These experiments establish that the electrophysiological phenotype of spiral ganglion neurons depends critically on the precise concentration of NT-3 and that the functional organization of this component of the peripheral auditory system results from a complex interplay between multiple kinds of neurotrophins and their cognate receptors.
Differential Vesicular Targeting and Time Course of Synaptic Secretion of the Mammalian Neurotrophins
Authors: Brigadski Tanja , Hartmann Matthias , Lessmann Volkmar
Published: August 2005

Neurotrophins are a family of secreted neuronal survival and plasticity factors comprising NGF, BDNF, neurotrophin-3 (NT-3), and NT-4. Whereas synaptic secretion of BDNF has been described, the routes of intracellular targeting and secretion of NGF, NT-3, and NT-4 in neurons are poorly understood.

To allow for a direct comparison of intracellular targeting and release properties, all four mammalian neurotrophins were expressed as green fluorescent protein fusion proteins in cultured rat hippocampal neurons. We show that BDNF and NT-3 are targeted more efficiently to dendritic secretory granules of the regulated pathway of secretion (BDNF, in 98% of cells; NT-3, 85%) than NGF (46%) and NT-4 (23%). For all NTs, the remaining cells showed targeting to the constitutive secretory pathway. Fusing the BDNF pre-pro sequence to NT-4 directed NT-4 more efficiently to the regulated pathway of secretion.

All neurotrophins, once directed to the regulated secretion pathway, were detected near synapsin I-positive presynaptic terminals and colocalized with PSD-95-DsRed (postsynaptic density-95-Discosoma red), suggesting postsynaptic targeting of the neurotrophins to glutamatergic synapses. Depolarization-induced release of all neurotrophins from synaptic secretory granules was slow (delay in onset, 10-30 s; τ = 120-307 s) compared with transmitter release kinetics monitored with FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)hexatrienyl)pyridinium dibromide] destaining (onset, <5 s; τ = 13 ± 2 s). Among the neurotrophins, NT-4 secretion was most rapid but still proceeded 10 times more slowly than transmitter secretion. Preincubation of neurons with monensin (neutralizing intragranular pH, thus solubilizing the peptide core) increased the speed of secretion of BDNF, NGF, and NT-3 to the value of NT-4. These data suggest that peptide core dissolution in secretory granules is the critical determinant of the speed of synaptic secretion of all mammalian NTs and that the speed of release is not compatible with fast transmitter-like actions of neurotrophins.
Strong Effects of Subphysiological Temperature on the Function and Plasticity of Mammalian Presynaptic Terminals
Authors: Micheva Kristina D. , Smith Stephen J.
Published: August 2005

Most cellular processes are known to be strongly temperature dependent. Nevertheless, a large fraction of studies of mammalian synaptic function have been and are performed near room temperature (i.e., at least 10°C below physiological temperature). Here, we examined the effects of temperature on presynaptic function in primary cultures of rat hippocampal neurons. FM dyes, VAMP (vesicle-associated membrane protein)-GFP (green fluorescent protein) transfection, and HRP uptake were used to quantify various aspects of synaptic vesicle recycling. Our results show that there are very substantial differences in synaptic vesicle recycling at physiological temperature as opposed to the common, lower experimental temperatures. At 37°C, compared with 23°C, the speed of both exocytosis and endocytosis was higher. The size of the recycling vesicle pool (in both number of vesicles and spatial extent) was twofold larger at 37°C. In addition, although repeated 10 Hz electrical stimulation caused an NMDA receptor-dependent enlargement (averaging 170%) of the measurable recycling vesicle pool at 23°C, the same stimulus repetition had no effect at 37°C. These results show that it is potentially misleading to extend conclusions drawn about vesicle function or presynaptic plasticity at lowered experimental temperature to physiological conditions and that much new experimental work at the higher physiological temperature range will be needed to understand the true parameters of presynaptic functions.
Experiential Effects of Appetitive and Nonappetitive Odors on Feeding Behavior in the Blowfly,Phormia regina: A Putative Role for Tyramine in Appetite Regulation
Authors: Nisimura Tomoyosi , Seto Atsushi , Nakamura Kyoko , Miyama Mayumi , Nagao Takashi , Tamotsu Satoshi , Yamaoka Ryohei , Ozaki Mamiko
Published: August 2005

In humans, appetite is affected by food experiences and food flavors. In the blowflyPhormia regina, we found that feeding threshold to sugar increased in the presence of the odor ofd-limonene and decreased in the presence of the odor of dithiothreitol (DTT). Using these odors as representative nonappetitive and appetitive flavors, we demonstrated the role played by tyramine (TA) in appetite regulation by experiences of food flavors. When fed with sucrose flavored withd-limonene for 5 d after emergence, flies showed subsequent decreased appetite to plain sucrose, whereas when they were fed with sucrose flavored by DTT they showed increased appetite. However, mushroom body (MB)-ablated flies did not show these patterns. This suggests that MB, one of the primary memory centers of the insect brain, is necessary for the flies to apply previous experiences of food flavors to appetitive learning behaviors. In addition, flies' previously acquired decreased or increased appetites showed parallel changes with both octopamine (OA) and tyramine levels in the brain. However, injection experiments with OA, TA, or their agonist and antagonist indicated that TA more directly mediates feeding threshold determination, which was affected by acquired memories of food flavors.
High-Concentration Rapid Transients of Glutamate Mediate Neural-Glial Communication via Ectopic Release
Authors: Matsui Ko , Jahr Craig E. , Rubio Maria E.
Published: August 2005

Until recently, communication from neurons to astrocytes was thought to be mediated by low-concentration transients of glutamate caused by spillover from the synaptic cleft. However, quantal events recorded in rat cerebellar Bergmann glial cells (BGs) have fast kinetics, comparable with those recorded in neurons. By combining outside-out patch recordings of BG AMPA receptors and quantitative electron microscopic analysis of glutamate receptor subunit 1 (GluR1) and GluR4 immunogold labeling measurements, at both the soma and membranes surrounding synapses, we estimate the absolute density of functional AMPA receptors. Using a kinetic model of BG AMPA receptors, we find that quantal events recorded in BGs are produced by high-concentration (∼1-1.5 mm), fast transients (∼0.5 ms decay) of glutamate, similar to transients within the synaptic cleft. Our results indicate that neural signaling to BGs is mediated by ectopic release of transmitter from presynaptic elements directly facing the BG membrane.
Optical Imaging of SI Topography in Anesthetized and Awake Squirrel Monkeys
Authors: Chen Li Min , Friedman Robert Mark , Roe Anna Wang
Published: August 2005

Orderly topographic maps in the primary somatosensory cortex (SI) serve as an anchor for our understanding of somatosensory cortical organization. However, this view is mostly based on data collected in the anesthetized animal. Less is known about these topographies in the awake primate. Even less is known about the relative activations of different subdivisions of SI (areas 3a, 3b, 1, and 2). Toward the goal of understanding the functional activation of SI, we conducted intrinsic signal optical imaging of areas 3b and 1 in awake squirrel monkeys. Monkeys were imaged repeatedly for a period of >2 years in awake and anesthetized states in response to vibrotactile and electrocutaneous stimuli presented to individual fingerpads. During this period, we found stable somatotopic maps in both the anesthetized and awake states, consistent with electrophysiologically recorded maps in areas 3b and 1 in the anesthetized state. In the awake animal, signal sizes were larger, but variability was greater, leading to decreased signal-to-noise ratios. Topographic activations were larger (in both area and amplitude) in the awake animal, suggesting either a less precise topography and/or more complex integration. This brings into question the role of a precise topographic map during behavior. In addition, whereas in the anesthetized animal strongest imaging signals were obtained from area 3b, in the awake animal, area 1 activation dominated over that in area 3b. Differences in relative dominance of area 3b versus area 1 suggest that inter-areal interactions in the alert animal differ substantially from that in the anesthetized animal.
The Two Isoforms of theCaenorhabditis elegansLeukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation
Authors: Ackley Brian D. , Harrington Robert J. , Hudson Martin L. , Williams Lisa , Kenyon Cynthia J. , Chisholm Andrew D. , Jin Yishi
Published: August 2005

Leukocyte-common antigen related (LAR)-like phosphatase receptors are conserved cell adhesion molecules that function in multiple developmental processes. TheCaenorhabditis elegans ptp-3gene encodes two LAR family isoforms that differ in the extracellular domain. We show here that the long isoform, PTP-3A, localizes specifically at synapses and that the short isoform, PTP-3B, is extrasynaptic. Mutations inptp-3cause defects in axon guidance that can be rescued by PTP-3B but not by PTP-3A. Mutations that specifically affectptp-3Ado not affect axon guidance but instead cause alterations in synapse morphology. Genetic double-mutant analysis is consistent withptp-3Aacting with the extracellular matrix component nidogen,nid-1, and the intracellular adaptor α-liprin,syd-2.nid-1andsyd-2are required for the recruitment and stability of PTP-3A at synapses, and mutations inptp-3ornid-1result in aberrant localization of SYD-2. Overexpression of PTP-3A is able to bypass the requirement fornid-1for the localization of SYD-2 and RIM. We propose that PTP-3A acts as a molecular link between the extracellular matrix and α-liprin during synaptogenesis.
Hippocampal Synaptic Metaplasticity Requires Inhibitory Autophosphorylation of Ca2+/Calmodulin-Dependent Kinase II
Authors: Zhang Lian , Kirschstein Timo , Sommersberg Britta , Merkens Malte , Manahan-Vaughan Denise , Elgersma Ype , Beck Heinz
Published: August 2005

Virtually all CNS synapses display the potential for activity-dependent long-term potentiation (LTP) and/or long-term depression (LTD). Intriguingly, the potential to exhibit LTP or LTD at many central synapses itself is powerfully modulated by previous synaptic activity. This higher-order form of plasticity has been termed metaplasticity. Here, we show that inhibitory autophosphorylation of Ca2+/calmodulin-dependent kinase II (CaMKII) is required for hippocampal metaplasticity at the lateral perforant path-dentate granule cell synapse. Brief 10 Hz priming, which does not affect basal synaptic transmission, caused a dramatic, pathway-specific and long-lasting (up to 18 h) reduction in subsequently evoked LTP at lateral perforant path synapses. In contrast, LTD was unaffected by priming. The induction of lateral perforant path metaplasticity required the activation of NMDA receptors during priming. In addition, metaplasticity was absent in knock-in mice expressing αCaMKII that cannot undergo inhibitory phosphorylation, indicating that inhibitory autophosphorylation of αCaMKII at threonines 305/306 is required for metaplasticity. Metaplasticity was not observed in the medial perforant pathway, consistent with the observation that CaMKII activity was not required for the induction of LTP at this synapse. Thus, modulation of αCaMKII activity via autophosphorylation at Thr305/Thr306 is a key mechanism for metaplasticity that may be of importance in the integration of temporally separated episodes of activity.
A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons
Authors: Lundkvist Gabriella B. , Kwak Yongho , Davis Erin K. , Tei Hajime , Block Gene D.
Published: August 2005

Generation of mammalian circadian rhythms involves molecular transcriptional and translational feedback loops. It is not clear how membrane events interact with the intracellular molecular clock or whether membrane activities are involved in the actual generation of the circadian rhythm. We examined the role of membrane potential and calcium (Ca2+) influx in the expression of the circadian rhythm of the clock genePeriod 1(Per1) within the rat suprachiasmatic nucleus (SCN), the master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization, caused by lowering the extracellular concentration of potassium or blocking Ca2+influx in SCN cultures by lowering [Ca2+], reversibly abolished the rhythmic expression ofPer1. In addition, the amplitude ofPer1expression was markedly decreased by voltage-gated Ca2+channel antagonists. A similar result was observed for mousePer1and PER2. Together, these results strongly suggest that a transmembrane Ca2+flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca2+influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.
Feedforward Inhibitory Control of Sensory Information in Higher-Order Thalamic Nuclei
Authors: Lavallée Philippe , Urbain Nadia , Dufresne Caroline , Bokor Hajnalka , Acsády László , Deschênes Martin
Published: August 2005

Sensory stimuli evoke strong responses in thalamic relay cells, which ensure a faithful relay of information to the neocortex. However, relay cells of the posterior thalamic nuclear group in rodents, despite receiving significant trigeminal input, respond poorly to vibrissa deflection. Here we show that sensory transmission in this nucleus is impeded by fast feedforward inhibition mediated by GABAergic neurons of the zona incerta. Intracellular recordings of posterior group neurons revealed that the first synaptic event after whisker deflection is a prominent inhibition. Whisker-evoked EPSPs with fast rise time and longer onset latency are unveiled only after lesioning the zona incerta. Excitation survives barrel cortex lesion, demonstrating its peripheral origin. Electron microscopic data confirm that trigeminal axons make large synaptic terminals on the proximal dendrites of posterior group cells and on the somata of incertal neurons. Thus, the connectivity of the system allows an unusual situation in which inhibition precedes ascending excitation resulting in efficient shunting of the responses. The dominance of inhibition over excitation strongly suggests that the paralemniscal pathway is not designed to relay inputs triggered by passive whisker deflection. Instead, we propose that this pathway operates through disinhibition, and that the posterior group forwards to the cerebral cortex sensory information that is contingent on motor instructions.
Src-Dependent Tyrosine Phosphorylation at the Tips of Growth Cone Filopodia Promotes Extension
Authors: Robles Estuardo , Woo Stephanie , Gomez Timothy M.
Published: August 2005

Extracellular cues guide axon outgrowth by activating intracellular signaling cascades that control the growth cone cytoskeleton. However, the spatial and temporal coordination of signaling intermediates remains essentially unknown. Live imaging of tyrosine phosphorylation in growth cones revealed dynamic phospho-tyrosine (PY) signals in filopodia that directly correlate with filopodial behavior. Local PY signals are generated at distal tips of filopodia during extension and are lost during retraction. Active Src family kinases localize to the tips of filopodia, and Src activity regulates both filopodial dynamics and local PY signaling. Positive guidance cues stimulate filopodial motility by locally increasing tyrosine phosphorylation in a cell division cycle 42 (Cdc42)-dependent manner. Locally reduced Src activity on one side of the growth cone generates an asymmetry in filopodial motility and PY signaling that promotes repulsive turning, suggesting that local changes in filopodial PY levels may underlie growth cone pathfinding decisions. p21-activated kinase (PAK), a Cdc42 effector whose activity is regulated by Src phosphorylation, also localizes to the tips of extending filopodia and controls filopodial motility. Coordinated activation of cytoskeletal effector proteins by GTPase binding and Src-mediated tyrosine phosphorylation may function to produce specific growth cone behaviors in response to guidance cues.
Some Intellectual Genealogies for the Concept of Everyday Resistance
Authors: SIVARAMAKRISHNAN K.
Published: August 2005

Concerns with how cultural factors influenced agrarian social change remained an abiding interest in the work of James Scott. I begin by sketching out the context of debates in Marxist theory, development studies, and social and political anthropology that, during the 1980s, turned to relations between ideas, power, and processes of conflict and change in a world of new postcolonial nations and rapid agrarian development. In the article, then, I carefully examine the ideas Scott developed about resistance and hegemony in conversation with the work of E. P. Thompson. Tracing the genealogy of Scott's ideas about hegemony and rural social protest, I comment in some detail on the literature on resistance that arose in anthropology during the 1980s and the role of Scott's Weapons of the Weak (1985) in shaping that literature while interacting with Subaltern Studies (Guha 1982–87), studies of social movements, and examinations of power in interpersonal relations.
Making Forest of Bliss: The Film, the Book, the DVD, and the Breakthrough
Authors: COOPER TOM
Published: August 2005

Robert Gardner's and Àkos Östör's Making of Forest of Bliss (2002) is a combination book and DVD that contains eight teaching tools for better understanding Gardner's celebrated film Forest of Bliss. After the film was shot in 1985, filmmaker Gardner and anthropologist Östör recorded a conversation about each image and sound of the film while they screened it again in 1987, and remembered their filmmaking process on location in Benares, India. The feature length (89 minute) documentary about death ritual, reincarnation, the sacred Ganges River, and the very atmosphere of Benares is included as DVD, as are teaching tools such as frame grabs (still images from the film), a mathematically precise shot list, bibliography, important criticism and essays about the film, and the featured in‐depth conversation between filmmaker Gardner and anthropological advisor Östör. This essay articulates the unique breakthroughs in pedagogy, cross‐cultural studies, and multidisciplinary analysis such hybrid technology provides.
Spectral Properties of Selected UV‐blocking and UV‐transmitting Covering Materials with Application for Production of High‐value Crops in High Tunnels†
Authors: Krizek Donald T. , Clark H. David , Mirecki Roman M.
Published: August 2005

The spectral properties of selected UV‐blocking and UV‐transmitting covering materials were characterized by means of a UV–VIS spectroradiometer or a UV–VIS spectrometer to provide researchers and growers with guidelines for selecting suitable materials for use in studying the effects of ambient solar UV radiation on the production of tomatoes and other high‐value crops in high tunnels. A survey was made of a wide range of plastic covering materials to identify commercially available products that had the desired characteristics of transmitting high levels of photosynthetically active radiation and of being stable under ambient solar UV radiation. The study was focused on evaluating films that either blocked or transmitted UV wavelengths below 380 nm to determine comparative growth, yield and market quality and to provide a tool for integrated pest management. Based on this survey, two contrasting covering materials of similar thickness (0.152 mm) and durability (4‐year polyethylene), one a UV‐blocking film and the other a UV‐transmitting film, were selected and used to cover two high tunnels at Beltsville, MD. Spectroradiometric measurements were made to determine comparative spectral irradiance in these two high tunnels covered with these materials and under ambient solar UV radiation. Comparative measurements were also made of selected glass and plastic materials that have been used in UV exclusion studies.
Assessing Contaminant Transport Vulnerability in Complex Topography Using a Distributed Hydrologic Model
Authors: Martens Scott N. , Breshears David D.
Published: August 2005

Modeling of vadose zone hydrology is required to address a variety of applied problems in general and risk assessments associated with contaminants in particular. Risk assessments increasingly must focus on multisite, multipathway analyses as opposed to single‐site, single pathway analyses. Such assessments can be particularly challenging when contaminants are widely dispersed in complex topography. Here we highlight how a set of contaminated sites situated within complex topography can be effectively prioritized relative to vulnerability of contaminant transport from surface and subsurface flows. We used a distributed hydrologic model, SPLASH, to assess the lateral flows of surface and subsurface water following the simulation of a 100‐year precipitation event, which could correspond to an intense thunderstorm. Our case study was conducted in the North Ancho watershed of Los Alamos National Laboratory, in northern New Mexico, USA, an area with widely dispersed contaminants and diverse topography. Simulated surface flows generally exceeded subsurface flows by more than four orders of magnitude, indicating the relative importance of potential redistribution of contaminants by surface flows for this type of precipitation event. For the 18 potential contaminant release sites investigated, the maximum surface flow varied by more than an order of magnitude across the sites. Half of the sites had surface flows <25% of the maximum surface flow for a site, allowing for prioritization of those sites with the greatest vulnerability. Our results highlight how risks of contaminant transport can be effectively assessed in complex topography using distributed hydrologic modeling.
Ecohydrology Monitoring and Excavation of Semiarid Landfill Covers a Decade after Installation
Authors: Breshears David D. , Nyhan John W. , Davenport David W.
Published: August 2005

Landfill covers are intended to protect buried waste from water seepage and biointrusion for thirty to thousands of years, yet most cover studies are limited to a few years and do not directly investigate net changes in the soil profile that affect changing landfill performance. We evaluated water balances, vegetation cover, rooting patterns, and soil profiles of two landfill‐cover designs (two plots each) more than a decade after installation at semiarid Los Alamos National Laboratory, NM, USA: a conventional design of 20 cm of topsoil over compacted crushed‐tuff and an integrated design of 71 cm of topsoil over an engineered barrier designed to induce lateral flow (geotextile overlying 46 cm of gravel). Water balances for both designs had ~3% of precipitation as seepage; the integrated plots lost <1% of water as interflow, probably because the barrier interface had only a 5% slope. The conventional design had a net loss of stored soil water and proportionally more evapotranspiration than the integrated design. After more than a decade, (i) vegetation changes included increased biomass and species diversity on most plots, with proportionally fewer invading species and more extensive rooting in the integrated plots; (ii) the geotextile was largely unchanged; and (iii) infiltration and subsequent water penetration occurred primarily via macropores, including root channels and animal burrows. Both cover designs effectively minimized seepage during their initial decade, but observed effects of environmental processes such as succession and burrowing are expected to become progressively more important determinants of cover performance over additional decades.
Hydrologic Behavior of Unsaturated, Fractured Tuff: Interpretation and Modeling of a Wellbore Injection Test
Authors: Robinson Bruce A. , McLin Stephen G. , Viswanathan Hari S.
Published: August 2005

A previously reported injection zone test in the Tshirege Member of the Bandelier tuff has been interpreted and modeled using a variety of conceptual models ranging from a single continuum model (SCM) to a dual permeability model (DKM). The agreement of the numerical models and the data was quite acceptable, both qualitatively and quantitatively. The migration of water injected in an open interval of the wellbore exhibited flow that was controlled by gravity and, to a lesser extent, capillary forces. A sensitivity analysis showed that the behavior is well captured with laboratory determined hydrologic parameters and less so if rocks with higher capillary suction are simulated. More complex model formulations that explicitly account for fractures were also tested, but it was found that these models reproduce the field behavior only when parameters are selected that minimize the role of fractures. Therefore, the SCM is favored due to its simpler formulation and ease with which it is implemented in large‐scale flow and transport simulations. Discrete fracture simulations are used to illustrate that fractures are predicted to play a minor role in most subunits of the Bandelier tuff: high matrix permeability allows water entering fractures to quickly imbibe into the matrix, thereby reducing the tendency of these rocks to exhibit preferential fracture flow. In contrast, water flow through Basalts present on the Pajarito Plateau is predicted to be dominated by fractures.
Transport and Retention of Manure‐Borne Coliforms in Soil
Authors: Guber A. K. , Shelton D. R. , Pachepsky Ya. A.
Published: August 2005

Manure is a source of several bacterial pathogens that can potentially contribute to surface and groundwater contamination. Results from most bacterial transport studies in soils are only partially applicable to manure‐borne bacteria because microorganisms are released along with manure particulates as manure dissolves. The objective of this study was to compare transport of chloride ion, Escherichia coli (E. coli) and manure colloids in undisturbed soil columns with a well‐developed structure. Breakthrough column experiments were conducted with undisturbed, 20‐cm long Tyler soil columns from the A horizon. A pulse of 4% filtered bovine manure solution with E. coli and KCl was passed through the columns. Escherichia coli concentrations, chloride content, and turbidity were measured in influent and in effluent. Columns were cut into 2‐cm layers after the experiment to measure: (i) viable bacterial concentrations in pore solution and attached to soil; (ii) bulk density; (iii) water content. Companion batch experiments were performed to measure attachment of E. coli to soil in the presence of various amounts of manure. Escherichia coli attachment to soil decreased with increased manure content due to increased competition for attachment sites. Flow velocity affected E. coli transport and attachment to soil; there was relatively more attachment at slower flow velocity than at higher flow velocity. Escherichia coli attachment to soil was 18, 5, and 9% at flow velocities of 2.3, 8.4, and 9.3 cm d−1, respectively. Spatial variability in soil structure may result in large variations of pore water velocity and consequent differences in transport of manure particulates and bacteria under ponded infiltration.
Development and Application of Numerical Models to Estimate Fluxes through the Regional Aquifer beneath the Pajarito Plateau
Authors: Keating Elizabeth H. , Robinson Bruce A. , Vesselinov Velimir V.
Published: August 2005

Before recent drilling and characterization efforts in the vicinity of Los Alamos National Laboratory (LANL), conceptual models had been developed for recharge and discharge in the regional aquifer on the basis of sparse data. By integrating site‐wide data into a numerical model of the aquifer beneath the plateau we provide new insight into large‐scale aquifer properties and fluxes. This model is useful for understanding hydrologic mechanisms, assessing the magnitudes of different terms in the overall water budget, and, through sampling, for interpreting contaminant migration velocities in the overlying vadose zone. Modeling results suggest that the majority of water produced in well fields on the plateau, extracted at rates approaching 70% of total annual recharge, is derived from storage. This result is insensitive to assumptions about the percentage of total recharge that occurs in the near vicinity of water supply wells, because of strong anisotropy in the aquifer that prevents fast transport of local recharge to deeper units from which production occurs. Robust estimates of fluxes in the shallow portion of the aquifer immediately down gradient of LANL are important for contaminant transport simulations. Our model calculations show that these fluxes have decreased in the past 50 years by approximately 10% because of production in water supply wells. To explore the role of parameter uncertainty in flux prediction, a predictive analysis method was applied. Results showed that predicted flux through older basalts in the aquifer can vary by a factor of three because of uncertainty in aquifer properties and total recharge. We explored the impact of model parameter uncertainty on these results; however, the true uncertainty of our predictions, including the impact of possible conceptual model errors, is likely to be larger and is difficult to quantify.