bluuebunny/crossref_metadata_2025 huggingface dataset:
Responding to Unfair Offers Made by a Friend: Neuroelectrical Activity Changes in the Anterior Medial Prefrontal Cortex
Authors: Campanhã Camila , Minati Ludovico , Fregni Felipe , Boggio Paulo S.
Published: October 2011

When receiving unfair monetary offers from another person, the most common response is punishment. Existing literature on the Ultimatum Game indicates that individuals frequently refuse unfair offers even when this results in a loss for themselves. Here, we present behavioral and neurophysiological evidence demonstrating that friendship substantially modifies this response. When the proposer was a friend rather than an unknown person, unfair offers were less frequently rejected and the medial frontal negativity (MFN) typically associated with unfair offers was reversed to positive polarity. The underlying generators were located in inferior-mesial and right inferior- and medial-lateral frontal regions (BA10 and BA11). These findings highlight the fundamental role of the anterior prefrontal cortex in interpersonal economic interaction and, particularly, present new evidence on the effects of social distance on the MFN.
Marginalization in Neural Circuits with Divisive Normalization
Authors: Beck Jeffrey M. , Latham Peter E. , Pouget Alexandre
Published: October 2011

A wide range of computations performed by the nervous system involves a type of probabilistic inference known as marginalization. This computation comes up in seemingly unrelated tasks, including causal reasoning, odor recognition, motor control, visual tracking, coordinate transformations, visual search, decision making, and object recognition, to name just a few. The question we address here is: how could neural circuits implement such marginalizations? We show that when spike trains exhibit a particular type of statistics—associated with constant Fano factors and gain-invariant tuning curves, as is often reportedin vivo—some of the more common marginalizations can be achieved with networks that implement a quadratic nonlinearity and divisive normalization, the latter being a type of nonlinear lateral inhibition that has been widely reported in neural circuits. Previous studies have implicated divisive normalization in contrast gain control and attentional modulation. Our results raise the possibility that it is involved in yet another, highly critical, computation: near optimal marginalization in a remarkably wide range of tasks.
Inhibition Of Notch Activity Promotes Nonmitotic Regeneration of Hair Cells in the Adult Mouse Utricles
Authors: Lin Vincent , Golub Justin S. , Nguyen Tot Bui , Hume Clifford R. , Oesterle Elizabeth C. , Stone Jennifer S.
Published: October 2011

The capacity of adult mammals to regenerate sensory hair cells is not well defined. To explore early steps in this process, we examined reactivation of a transiently expressed developmental gene,Atoh1, in adult mouse utricles after neomycin-induced hair cell death in culture. Using an adenoviral reporter forAtoh1enhancer, we found thatAtoh1transcription is activated in some hair cell progenitors (supporting cells) 3 d after neomycin treatment. By 18 d after neomycin, the number of cells withAtoh1transcriptional activity increased significantly, but few cells acquired hair cell features (i.e., accumulated ATOH1 or myosin VIIa protein or developed stereocilia). Treatment with DAPT, an inhibitor of γ-secretase, reduced notch pathway activity, enhancedAtoh1transcriptional activity, and dramatically increased the number ofAtoh1-expressing cells with hair cell features, but only in the striolar/juxtastriolar region. Similar effects were seen with TAPI-1, an inhibitor of another enzyme required for notch activity (TACE). Division of supporting cells was rare in any control or DAPT-treated utricles. This study shows that mature mammals have a natural capacity to initiate vestibular hair cell regeneration and suggests that regional notch activity is a significant inhibitor of direct transdifferentiation of supporting cells into hair cells following damage.
In VivoImaging of Intersynaptic Vesicle Exchange Using VGLUT1VenusKnock-In Mice
Authors: Herzog Etienne , Nadrigny Fabien , Silm Katlin , Biesemann Christoph , Helling Imke , Bersot Tiphaine , Steffens Heinz , Schwartzmann Richard , Nägerl U. Valentin , El Mestikawy Salah , Rhee JeongSeop , Kirchhoff Frank , Brose Nils
Published: October 2011

The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many synapses in the mammalian brain. Due to its function and selective localization, VGLUT1 is one of the most specific markers for glutamatergic synaptic vesicles. It has been used widely to identify glutamatergic synapses, and its expression levels are tightly correlated with changes in quantal size, modulations of synaptic plasticity, and corresponding behaviors. We generated a fluorescent VGLUT1Venusknock-in mouse for the analysis of VGLUT1 and glutamatergic synaptic vesicle trafficking. The mutation does not affect glutamatergic synapse function, and thus the new mouse model represents a universal tool for the analysis of glutamatergic transmitter systems in the forebrain. Previous studies demonstrated synaptic vesicle exchange between terminalsin vitro. Using the VGLUT1Venusknock-in, we show that synaptic vesicles are dynamically shared among boutons in the cortex of micein vivo. We provide a detailed analysis of synaptic vesicle sharingin vitro, and show that network homeostasis leads to dynamic scaling of synaptic VGLUT1 levels.
Enhanced Oscillatory Activity in the Hippocampal–Prefrontal Network Is Related to Short-Term Memory Function after Early-Life Seizures
Authors: Kleen Jonathan K. , Wu Edie X. , Holmes Gregory L. , Scott Rod C. , Lenck-Santini Pierre-Pascal
Published: October 2011

Neurological insults during development are associated with later impairments in learning and memory. Although remedial training can help restore cognitive function, the neural mechanisms of this recovery in memory systems are largely unknown. To examine this issue, we measured electrophysiological oscillatory activity in the hippocampus (both CA3 and CA1) and prefrontal cortex of adult rats that had experienced repeated seizures in the first weeks of life, while they were remedially trained on a delayed-nonmatch-to-sample memory task. Seizure-exposed rats showed initial difficulties learning the task but performed similarly to control rats after extra training. Whole-session analyses illustrated enhanced theta power in all three structures while seizure rats learned response tasks before the memory task. While performing the memory task, dynamic oscillation patterns revealed that prefrontal cortex theta power was increased among seizure-exposed rats. This enhancement appeared after the first memory-training steps using short delays and plateaued at the most difficult steps, which included both short and long delays. Further, seizure rats showed enhanced CA1–prefrontal cortex theta coherence in correct trials compared with incorrect trials when long delays were imposed, suggesting increased hippocampal–prefrontal cortex synchrony for the task in this group when memory demand was high. Seizure-exposed rats also showed heightened gamma power and coherence among all three structures during the trials. Our results demonstrate the first evidence of hippocampal–prefrontal enhancements following seizures in early development. Dynamic compensatory changes in this network and interconnected circuits may underpin cognitive rehabilitation following other neurological insults to higher cognitive systems.
The Role of PSD-95 and Cypin in Morphological Changes in Dendrites Following Sublethal NMDA Exposure
Authors: Tseng Chia-Yi , Firestein Bonnie L.
Published: October 2011

Focal swelling or varicosity formation in dendrites and loss of dendritic spines are the earliest indications of glutamate-induced excitotoxicity. Although it is known that microtubule dynamics play a role in varicosity formation, very little is known about the proteins that directly impact microtubules during focal swelling and dendritic spine loss. Our laboratory has recently reported that the postsynaptic protein PSD-95 and its cytosolic interactor (cypin) regulate the patterning of dendrites in hippocampal neurons. Cypin promotes microtubule assembly, and PSD-95 disrupts microtubule organization. Thus, we hypothesized that cypin and PSD-95 may play a role in altering dendrite morphology and spine number in response to sublethal NMDA-induced excitotoxicity. Using anin vitromodel of glutamate-induced toxicity in rat hippocampal cultures, we found that cypin overexpression or PSD-95 knockdown increases the percentage of neurons with varicosities and the number of varicosities along dendrites, decreases the size of varicosities after sublethal NMDA exposure, and protects neurons from NMDA-induced death. In contrast, cypin knockdown or PSD-95 overexpression results in opposite effects. We further show that cypin regulates the density of spines/filopodia: cypin overexpression decreases the number of protrusions per micrometer of dendrite while cypin knockdown results in an opposite effect. Cypin overexpression and PSD-95 knockdown attenuate NMDA-promoted decreases in protrusion density. Thus, we have identified a novel pathway by which the microtubule cytoskeleton is regulated during sublethal changes to dendrites.
BDNF-Induced Increase of PSD-95 in Dendritic Spines Requires Dynamic Microtubule Invasions
Authors: Hu Xindao , Ballo Lauren , Pietila Lauren , Viesselmann Chris , Ballweg Jason , Lumbard Derek , Stevenson Matt , Merriam Elliott , Dent Erik W.
Published: October 2011

Microtubules (MTs) are capable of entering dendritic spines in mature hippocampal neurons through dynamic polymerization. Although these MT invasions are directly associated with neuronal activity, their function remains unknown. Here we demonstrate in mouse hippocampal neurons that MT entries into spines regulate the increase in postsynaptic density-95 (PSD-95) protein after brain-derived neurotrophic factor (BDNF) treatment. Using multiwavelength total internal reflectance fluorescence microscopy, we show that BDNF prolonged the average MT dwell time in spines and that this effect was dependent on TrkB receptor activation. Further examination revealed that peaks of MT polymerization into spines corresponded to rapid PSD-95 increases in the spine head. Over time, spines targeted by MTs after BDNF application, but not before, showed a robust increase in PSD-95. Conversely, spines completely devoid of MT invasions showed no significant change in the level of PSD-95. Pharmacological inhibition of MT dynamics abolished the BDNF-induced increase in PSD-95. Together, these results support the hypothesis that the well known increase in PSD-95 within spines after BDNF treatment is dependent on MT invasions of dendritic spines. Thus, our study provides a direct link between dynamic MTs and the postsynaptic structure, and provides a functional role for MT invasion of dendritic spines.
Caltubin, a Novel Molluscan Tubulin-Interacting Protein, Promotes Axonal Growth and Attenuates Axonal Degeneration of Rodent Neurons
Authors: Nejatbakhsh Nasrin , Guo Cong-Hui , Lu Tom Z. , Pei Lin , Smit August B. , Sun Hong-Shuo , van Kesteren Ronald E. , Feng Zhong-Ping
Published: October 2011

Axotomized central neurons of most invertebrate species demonstrate a strong regenerative capacity, and as such may provide valuable molecular insights and new tools to promote axonal regeneration in injured mammalian neurons. In this study, we identified a novel molluscan protein, caltubin, ubiquitously expressed in central neurons ofLymnaea stagnalisand locally synthesized in regenerating neurites. Reduction of caltubin levels by gene silencing inhibits the outgrowth and regenerative ability of adultLymnaeaneurons and decreases local α- and β-tubulin levels in neurites. Caltubin binds to α- and/or β-tubulin in bothLymnaeaand rodent neurons. Expression of caltubin in PC12 cells and mouse cortical neurons promotes NGF-induced axonal outgrowth and attenuates axonal retraction after injury. This is the first study illustrating that a xenoprotein can enhance outgrowth and prevent degeneration of injured mammalian neurons. These results may open up new avenues in molecular repair strategies through the insertion of molecular components of invertebrate regenerative pathways into mammalian neurons.
The Sonar Aperture and Its Neural Representation in Bats
Authors: Heinrich Melina , Warmbold Alexander , Hoffmann Susanne , Firzlaff Uwe , Wiegrebe Lutz
Published: October 2011

As opposed to visual imaging, biosonar imaging of spatial object properties represents a challenge for the auditory system because its sensory epithelium is not arranged along space axes. For echolocating bats, object width is encoded by the amplitude of its echo (echo intensity) but also by the naturally covarying spread of angles of incidence from which the echoes impinge on the bat's ears (sonar aperture). It is unclear whether bats use the echo intensity and/or the sonar aperture to estimate an object's width. We addressed this question in a combined psychophysical and electrophysiological approach. In three virtual-object playback experiments, bats of the speciesPhyllostomus discolorhad to discriminate simple reflections of their own echolocation calls differing in echo intensity, sonar aperture, or both. Discrimination performance for objects with physically correct covariation of sonar aperture and echo intensity (“object width”) did not differ from discrimination performances when only the sonar aperture was varied. Thus, the bats were able to detect changes in object width in the absence of intensity cues. The psychophysical results are reflected in the responses of a population of units in the auditory midbrain and cortex that responded strongest to echoes from objects with a specific sonar aperture, regardless of variations in echo intensity. Neurometric functions obtained from cortical units encoding the sonar aperture are sufficient to explain the behavioral performance of the bats. These current data show that the sonar aperture is a behaviorally relevant and reliably encoded cue for object size in bat sonar.
Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis
Authors: Tampellini Davide , Rahman Nawreen , Lin Michael T. , Capetillo-Zarate Estibaliz , Gouras Gunnar K.
Published: October 2011

A central question in Alzheimer's disease (AD) research is what role β-amyloid peptide (Aβ) plays in synaptic dysfunction. Synaptic activity increases Aβ secretion, potentially inhibiting synapses, but also decreases intraneuronal Aβ, protecting synapses. We now show that levels of secreted Aβ fall with time in culture in neurons of AD-transgenic mice, but not wild-type mice. Moreover, the ability of synaptic activity to elevate secreted Aβ and reduce intraneuronal Aβ becomes impaired in AD-transgenic but not wild-type neurons with time in culture. We demonstrate that synaptic activity promotes an increase in the Aβ-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aβ42. Remarkably, AD-transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Aβ and reduce intraneuronal Aβ has important implications for the pathogenesis and treatment of AD.
Spatiotemporal Variation of Multiple Neurophysiological Signals in the Primary Motor Cortex during Dexterous Reach-to-Grasp Movements
Authors: Mollazadeh Mohsen , Aggarwal Vikram , Davidson Adam G. , Law Andrew J. , Thakor Nitish V. , Schieber Marc H.
Published: October 2011

To examine the spatiotemporal distribution of discriminable information about reach-to-grasp movements in the primary motor cortex upper extremity representation, we implanted four microelectrode arrays in the anterior bank and lip of the central sulcus in each of two monkeys. We used linear discriminant analysis to compare information, quantified as decoding accuracy, contained in various neurophysiological signals. For all signal types, decoding accuracy increased immediately after the movement cue, peaked around movement onset, and declined during the static hold. Spike recordings and local field potential (LFP) time domain amplitude provided more discriminable information than LFP frequency domain power. Discriminable information on movement type was distributed evenly across recording sites by LFP amplitude and 1–4 Hz power but unevenly by 100–170 Hz power and spike recordings. These latter two signal types provided higher decoding accuracies closer to the hemispheric surface than deep in the anterior bank and also provided accuracies that varied along the central sulcus. This variation in the distribution of movement-type information may be related to differences in the rostral versus caudal regions of the primary motor cortex and to its underlying somatotopic organization. The even distribution of information by LFP amplitude and 1–4 Hz power compared with the more localized distribution by 100–170 Hz power and spikes suggest that these different neurophysiological signals reflect different underlying processes that distribute information through the motor cortex during reach-to-grasp movements.
Individual Differences in Verbal Abilities Associated with Regional Blurring of the Left Gray and White Matter Boundary
Authors: Blackmon Karen , Halgren Eric , Barr William B. , Carlson Chad , Devinsky Orrin , DuBois Jonathan , Quinn Brian T. , French Jacqueline , Kuzniecky Ruben , Thesen Thomas
Published: October 2011

Blurring of the cortical gray and white matter border on MRI is associated with normal aging, pathological aging, and the presence of focal cortical dysplasia. However, it remains unclear whether normal variations in signal intensity contrast at the gray and white matter junction reflect the functional integrity of subjacent tissue. This study explores the relationship between verbal abilities and gray and white matter contrast (GWC) in healthy human adults. Participants were scanned at 3 T MRI and administered standardized measures of verbal expression and verbal working memory. GWC was estimated by calculating the non-normalized T1 image intensity contrast above and below the cortical gray/white matter interface. Spherical averaging and whole-brain correlational analyses were performed. Sulcal regions exhibited higher contrast compared to gyral regions. We found a strongly lateralized and regionally specific profile with reduced verbal expression abilities associated with blurring in left hemisphere inferior frontal cortex and temporal pole. Reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomical substrates of cognition in healthy and diseased populations.
Early Emergence of Neural Activity in the Developing Mouse Enteric Nervous System
Authors: Hao Marlene M. , Boesmans Werend , Van den Abbeel Valentine , Jennings Ernest A. , Bornstein Joel C. , Young Heather M. , Vanden Berghe Pieter
Published: October 2011

Neurons of the enteric nervous system (ENS) arise from neural crest cells that migrate into and along the developing gastrointestinal tract. A subpopulation of these neural-crest derived cells express pan-neuronal markers early in development, shortly after they first enter the gut. However, it is unknown whether these early enteric “neurons” are electrically active. In this study we used live Ca2+imaging to examine the activity of enteric neurons from mice at embryonic day 11.5 (E11.5), E12.5, E15.5, and E18.5 that were dissociated and cultured overnight. PGP9.5-immunoreactive neurons from E11.5 gut cultures responded to electrical field stimulation with fast [Ca2+]itransients that were sensitive to TTX and ω-conotoxin GVIA, suggesting roles for voltage-gated Na+channels and N-type voltage-gated Ca2+channels. E11.5 neurons were also responsive to the nicotinic cholinergic agonist, dimethylphenylpiperazinium, and to ATP. In addition, spontaneous [Ca2+]itransients were present. Similar responses were observed in neurons from older embryonic gut. Whole-cell patch-clamp recordings performed on E12.5 enteric neurons after 2–10 h in culture revealed that these neurons fired both spontaneous and evoked action potentials. Together, our results show that enteric neurons exhibit mature forms of activity at early stages of ENS development. This is the first investigation to directly examine the presence of neural activity during enteric neuron development. Along with the spinal cord and hindbrain, the ENS appears to be one of the earliest parts of the nervous system to exhibit electrical activity.
Modulation of Microsaccades in Monkey during a Covert Visual Attention Task
Authors: Hafed Ziad M. , Lovejoy Lee P. , Krauzlis Richard J.
Published: October 2011

The use of awake, fixating monkeys in neuroscience has allowed significant advances in understanding numerous brain functions. However, fixation is an active process, with the occurrence of incessant eye movements, including rapid ones called microsaccades. Even though microsaccades have been shown to be modulated by stimulus and cognitive processes in humans, it is not known to what extent these results are similar in monkeys or why they occur. Here, we analyzed the stimulus-, context-, and attention-related changes in microsaccades while monkeys performed a challenging visual attention task. The distributions of microsaccade times were highly stereotypical across thousands of trials in the task. Moreover, in epochs of the task in which animals anticipated the occurrence of brief stimulus probes, microsaccade frequency decreased to a rate of less than one movement per second even on long multisecond trials. These effects were explained by the observation that microsaccades occurring at the times of the brief probes were sometimes associated with reduced perceptual performance. Microsaccade directions also exhibited temporal modulations related to the attentional demands of the task, like earlier studies in humans, and were more likely to be directed toward an attended location on successfully performed trials than on unsuccessfully completed ones. Our results show that microsaccades in nonhuman primates are correlated with the allocation of stimulus-evoked and sustained covert attention. We hypothesize that involvement of the superior colliculus in microsaccade generation and attentional allocation contributes to these observations. More importantly, our results clarify the potential role of these eye movements in modifying behavior and neural activity.
Differential Modulation of Excitatory and Inhibitory Striatal Synaptic Transmission by Histamine
Authors: Ellender Tommas J. , Huerta-Ocampo Icnelia , Deisseroth Karl , Capogna Marco , Bolam J. Paul
Published: October 2011

Information processing in the striatum is critical for basal ganglia function and strongly influenced by neuromodulators (e.g., dopamine). The striatum also receives modulatory afferents from the histaminergic neurons in the hypothalamus which exhibit a distinct diurnal rhythm with high activity during wakefulness, and little or no activity during sleep. In view of the fact that the striatum also expresses a high density of histamine receptors, we hypothesized that released histamine will affect striatal function. We studied the role of histamine on striatal microcircuit function by performing whole-cell patch-clamp recordings of neurochemically identified striatal neurons combined with electrical and optogenetic stimulation of striatal afferents in mouse brain slices. Bath applied histamine had many effects on striatal microcircuits. Histamine, acting at H2receptors, depolarized both the direct and indirect pathway medium spiny projection neurons (MSNs). Excitatory, glutamatergic input to both classes of MSNs from both the cortex and thalamus was negatively modulated by histamine acting at presynaptic H3receptors. The dynamics of thalamostriatal, but not corticostriatal, synapses were modulated by histamine leading to a facilitation of thalamic input. Furthermore, local inhibitory input to both classes of MSNs was negatively modulated by histamine. Subsequent dual whole-cell patch-clamp recordings of connected pairs of striatal neurons revealed that only lateral inhibition between MSNs is negatively modulated, whereas feedforward inhibition from fast-spiking GABAergic interneurons onto MSNs is unaffected by histamine. These findings suggest that the diurnal rhythm of histamine release entrains striatal function which, during wakefulness, is dominated by feedforward inhibition and a suppression of excitatory drive.
Small Heat-Shock Protein HSPB1 Mutants Stabilize Microtubules in Charcot-Marie-Tooth Neuropathy
Authors: Almeida-Souza Leonardo , Asselbergh Bob , d'Ydewalle Constantin , Moonens Kristof , Goethals Sofie , de Winter Vicky , Azmi Abdelkrim , Irobi Joy , Timmermans Jean-Pierre , Gevaert Kris , Remaut Han , Van Den Bosch Ludo , Timmerman Vincent , Janssens Sophie
Published: October 2011

Mutations in the small heat shock protein HSPB1 (HSP27) are causative for Charcot-Marie-Tooth (CMT) neuropathy. We previously showed that a subset of these mutations displays higher chaperone activity and enhanced affinity to client proteins. We hypothesized that this excessive binding property might cause the HSPB1 mutant proteins to disturb the function of proteins essential for the maintenance or survival of peripheral neurons. In the present work, we explored this hypothesis further and compared the protein complexes formed by wild-type and mutant HSPB1. Tubulin came out as the most striking differential interacting protein, with hyperactive mutants binding more strongly to both tubulin and microtubules. This anomalous binding leads to a stabilization of the microtubule network in a microtubule-associated protein-like manner as reflected by resistance to cold depolymerization, faster network recovery after nocodazole treatment, and decreased rescue and catastrophe rates of individual microtubules. In a transgenic mouse model for mutant HSPB1 that recapitulates all features of CMT, we could confirm the enhanced interaction of mutant HSPB1 with tubulin. Increased stability of the microtubule network was also clear in neurons isolated from these mice. Since neuronal cells are particularly vulnerable to disturbances in microtubule dynamics, this mechanism might explain the neuron-specific CMT phenotype caused by HSPB1 mutations.
Molecular and Cellular Organization of the Taste System in theDrosophilaLarva
Authors: Kwon Jae Young , Dahanukar Anupama , Weiss Linnea A. , Carlson John R.
Published: October 2011

We examine the molecular and cellular basis of taste perception in theDrosophilalarva through a comprehensive analysis of the expression patterns of all 68 Gustatory receptors (Grs).Gr-GAL4lines representing each Gr are examined, and 39 show expression in taste organs of the larval head, including the terminal organ (TO), the dorsal organ (DO), and the pharyngeal organs. A receptor-to-neuron map is constructed. The map defines 10 neurons of the TO and DO, and it identifies 28 receptors that map to them. Each of these neurons expresses a unique subset ofGr-GAL4drivers, except for two neurons that express the same complement. All of these neurons express at least two drivers, and one neuron expresses 17. Many of the receptors map to only one of these cells, but some map to as many as six. Conspicuously absent from the roster ofGr-GAL4drivers expressed in larvae are those of the sugar receptor subfamily. Coexpression analysis suggests that most larval Grs act in bitter response and that there are distinct bitter-sensing neurons. A comprehensive analysis of central projections confirms that sensory information collected from different regions (e.g., the tip of the head vs the pharynx) is processed in different regions of the suboesophageal ganglion, the primary taste center of the CNS. Together, the results provide an extensive view of the molecular and cellular organization of the larval taste system.
Microglia and Memory: Modulation by Early-Life Infection
Authors: Williamson Lauren L. , Sholar Paige W. , Mistry Rishi S. , Smith Susan H. , Bilbo Staci D.
Published: October 2011

The proinflammatory cytokine interleukin-1β (IL-1β) is critical for normal hippocampus (HP)-dependent cognition, whereas high levels can disrupt memory and are implicated in neurodegeneration. However, the cellular source of IL-1β during learning has not been shown, and little is known about the risk factors leading to cytokine dysregulation within the HP. We have reported that neonatal bacterial infection in rats leads to marked HP-dependent memory deficits in adulthood. However, deficits are only observed if unmasked by a subsequent immune challenge [lipopolysaccharide (LPS)] around the time of learning. These data implicate a long-term change within the immune system that, upon activation with the “second hit,” LPS, acutely impacts the neural processes underlying memory. Indeed, inhibiting brain IL-1β before the LPS challenge prevents memory impairment in neonatally infected (NI) rats. We aimed to determine the cellular source of IL-1β during normal learning and thereby lend insight into the mechanism by which this cytokine is enduringly altered by early-life infection. We show for the first time that CD11b+enriched cells are the source of IL-1β during normal HP-dependent learning. CD11b+cells from NI rats are functionally sensitized within the adult HP and produce exaggerated IL-1βex vivocompared with controls. However, an exaggerated IL-1β responsein vivorequires LPS before learning. Moreover, preventing microglial activation during learning prevents memory impairment in NI rats, even following an LPS challenge. Thus, early-life events can significantly modulate normal learning-dependent cytokine activity within the HP, via a specific, enduring impact on brain microglial function.
Coordination of Distinct Motor Structures through Remote Axonal Coupling of Projection Interneurons
Authors: Jing Jian , Sasaki Kosei , Perkins Matthew H. , Siniscalchi Michael J. , Ludwar Bjoern C. , Cropper Elizabeth C. , Weiss Klaudiusz R.
Published: October 2011

Complex behaviors often require coordinated movements of dissimilar motor structures. The underlying neural mechanisms are poorly understood. We investigated cycle-by-cycle coordination of two dissimilar feeding structures inAplysia californica: the external lips and the internal radula. During feeding, the lips open while the radula protracts. Lip and radula motoneurons are located in the cerebral and buccal ganglia, respectively, and radula motoneurons are controlled by a well characterized buccal central pattern generator (CPG). Here, we examined whether the three electrically coupled lip motoneurons C15/16/17 are controlled by the buccal CPG or by a previously postulated cerebral CPG. Two buccal–cerebral projection interneurons, B34 and B63, which are part of the buccal CPG and mediate radula protraction, monosynaptically excite C15/16/17. Recordings from the B34 axon in the cerebral ganglion demonstrate its direct electrical coupling with C15/16/17, eliminating the need for a cerebral CPG. Moreover, when the multifunctional buccal CPG generates multiple forms of motor programs due to the activation of two inputs, the command-like neuron CBI-2 and the esophageal nerve (EN), C15/16 exhibit activity patterns that are distinct from C17. These distinct activity patterns result from combined activity of B34 and B63 and their differential excitation of C15/16 versus C17. In more general terms, we identified neuronal mechanisms that allow a single CPG to coordinate the phasing and activity of remotely located motoneurons innervating distinct structures that participate in the production of different motor outputs. We also demonstrated that axodendritic electrical coupling by projection interneurons plays a pivotal role in coordinating activity of these remotely located neurons.
Skeletal Muscle IP3R1Receptors Amplify Physiological and Pathological Synaptic Calcium Signals
Authors: Zhu Haipeng , Bhattacharyya Bula J. , Lin Hong , Gomez Christopher M.
Published: October 2011

Ca2+release from internal stores is critical for mediating both normal and pathological intracellular Ca2+signaling. Recent studies suggest that the inositol 1,4,5-triphosphate (IP3) receptor mediates Ca2+release from internal stores upon cholinergic activation of the neuromuscular junction (NMJ) in both physiological and pathological conditions. Here, we report that the type I IP3receptor (IP3R1)-mediated Ca2+release plays a crucial role in synaptic gene expression, development, and neuromuscular transmission, as well as mediating degeneration during excessive cholinergic activation. We found that IP3R1-mediated Ca2+release plays a key role in early development of the NMJ, homeostatic regulation of neuromuscular transmission, and synaptic gene expression. Reducing IP3R1-mediated Ca2+release via siRNA knockdown or IP3R blockers in C2C12 cells decreased calpain activity and prevented agonist-induced acetylcholine receptor (AChR) cluster dispersal. In fully developed NMJ in adult muscle, IP3R1knockdown or blockade effectively increased synaptic strength at presynaptic and postsynaptic sites by increasing both quantal release and expression of AChR subunits and other NMJ-specific genes in a pattern resembling muscle denervation. Moreover, in two mouse models of cholinergic overactivity and NMJ Ca2+overload, anti-cholinesterase toxicity and the slow-channel myasthenic syndrome (SCS), IP3R1knockdown eliminated NMJ Ca2+overload, pathological activation of calpain and caspase proteases, and markers of DNA damage at subsynaptic nuclei, and improved both neuromuscular transmission and clinical measures of motor function. Thus, blockade or genetic silencing of muscle IP3R1may be an effective and well tolerated therapeutic strategy in SCS and other conditions of excitotoxicity or Ca2+overload.
Spinal Cord Toll-Like Receptor 4 Mediates Inflammatory and Neuropathic Hypersensitivity in Male But Not Female Mice
Authors: Sorge Robert E. , LaCroix-Fralish Michael L. , Tuttle Alexander H. , Sotocinal Susana G. , Austin Jean-Sebastien , Ritchie Jennifer , Chanda Mona Lisa , Graham Allyson C. , Topham Lucas , Beggs Simon , Salter Michael W. , Mogil Jeffrey S.
Published: October 2011

The innate immune system is increasingly appreciated to play an important role in the mediation of chronic pain, and one molecule implicated in this process is the Toll-like receptor 4 (TLR4). Here, using pharmacological and genetic manipulations, we found that activating TLR4 in the spinal cord, with the agonist lipopolysaccharide (LPS), causes robust mechanical allodynia but only in male mice. Spinal LPS had no pain-producing effect in female mice. TLR4 also has a sex-specific role in inflammatory (complete Freund's adjuvant) and neuropathic (spared nerve injury) pain: pain behaviors were TLR4 dependent in males but TLR4 independent in females. The sex differences appear to be specific to the spinal cord, as LPS administered to the brain or the hindpaw produces equivalent allodynia in both sexes, and specific to pain, as intrathecal LPS produces equivalent hypothermia in both sexes. The involvement of TLR4 in pain behaviors in male mice is dependent on testosterone, as shown by gonadectomy and hormone replacement. We found no sex differences in spinalTlr4gene expression at baseline or after LPS, suggesting the existence of parallel spinal pain-processing circuitry in female mice not involving TLR4.
Neuron and Sensory Epithelial Cell Fate Is Sequentially Determined by Notch Signaling in Zebrafish Lateral Line Development
Authors: Mizoguchi Takamasa , Togawa Satoshi , Kawakami Koichi , Itoh Motoyuki
Published: October 2011

Sensory systems are specialized to recognize environmental changes. Sensory organs are complex structures composed of different cell types, including neurons and sensory receptor cells, and how these organs are generated is an important question in developmental neurobiology.

The posterior lateral line (pLL) is a simple sensory system in fish and amphibians that detects changes in water motion. It consists of neurons and sensory receptor hair cells, both of which are derived from the cranial ectoderm preplacodal region. However, it is not clearly understood how neurons and the sensory epithelium develop separately from the same preplacodal progenitors.

We found that the numbers of posterior lateral line ganglion (pLLG) neurons, which are marked byneurodexpression, increased in embryos with reduced Notch activity, but the forced activation of Notch reduced their number, suggesting that Notch-mediated lateral inhibition regulates the pLLG cell fate in zebrafish. By fate-mapping analysis, we found that cells adjacent to the pLLG neurons in the pre-pLL placodal region gave rise to the anterior part of the pLL primordium (i.e., sensory epithelial progenitor cells), and that the choice of cell fate between pLLG neuron or pLL primordium was regulated by Notch signaling. Since Notch signaling also affects hair cell fate determination at a later stage, our study suggests that Notch signaling has dual, time-dependent roles in specifying multiple cell types during pLL development.
Nicotinic Acetylcholine Receptor Stability at the NMJ Deficient in α-SyntrophinIn Vivo
Authors: Martinez-Pena y Valenzuela Isabel , Mouslim Chakib , Pires-Oliveira Marcelo , Adams Marvin E. , Froehner Stanley C. , Akaaboune Mohammed
Published: October 2011

α-Syntrophin (α-syn), a scaffold protein, links signaling molecules to the dystrophin–glycoprotein complex. Absence of α-syn from the DGC is known to lead to structurally aberrant neuromuscular junctions (NMJs) with few acetylcholine receptors (AChRs) clustered at synaptic sites. Using α-syn knock-out mice, we show that during the first postnatal week, α-syn is not required for synapse formation. However, at postnatal day 6 (P6)–P7, the structural integrity of the postsynaptic apparatus is altered, the turnover rate of AChRs increases significantly, and the number/density of AChRs is impaired. At the adult α-syn−/−NMJ, the turnover rate of AChRs is ∼4 times faster than wild-type synapses, and most removed receptors are targeted to degradation as few AChRs recycled to synaptic sites. Biochemical analyses show that in muscle cells of adult knock-out α-syn mice, total AChRs and scaffold protein rapsyn are significantly reduced, the 89 kDa and 75 kDa isoforms of tyrosine phosphorylated α-dystrobrevin (α-dbn) 1 (which are required for the maintenance and stability of AChR in α-dbn−/−synapses) are barely detectable. Electroporation of GFP-α-dbn1 in α-syn−/−muscle cells partially restored receptor density, turnover rate, and the structural integrity of the postsynaptic apparatus, whereas expression of rapsyn-GFP failed to rescue the α-syn−/−synaptic phenotype. These results demonstrate that α-syn is required for the maturation and stability of the postsynaptic apparatus and suggest that α-syn may act via α-dbn1.
FGF Signaling Expands Embryonic Cortical Surface Area by Regulating Notch-Dependent Neurogenesis
Authors: Rash Brian G. , Lim H. David , Breunig Joshua J. , Vaccarino Flora M.
Published: October 2011

The processes regulating cortical surface area expansion during development and evolution are unknown. We show that loss of function of all fibroblast growth factor receptors (FgfRs) expressed at the earliest stages of cortical development causes severe deficits in surface area growth by embryonic day 12.5 (E12.5) in the mouse. In FgfR mutants, accelerated production of neurons led to severe loss of radial progenitors and premature termination of neurogenesis. Nevertheless, these mutants showed remarkably little change in cortical layer structure. Birth-dating experiments indicated that a greater proportion of layer fates was generated during early neurogenic stages, revealing that FgfR activity normally slows the temporal progression of cortical layer fates. Electroporation of a dominant-negative FgfR at E11.5 increased cortical neurogenesis in normal mice—an effect that was blocked by simultaneous activation of the Notch pathway. Together with changes in the expression of Notch pathway genes in FgfR mutant embryos, these findings indicate that Notch lies downstream of FgfR signaling in the same pathway regulating cortical neurogenesis and begin to establish a mechanism for regulating cortical surface expansion.
Zur karthagischen Strategie im 2. römisch-karthagischen Krieg
Authors: Barceló Pedro
Published: October 2011

Einen unverstellten Blick auf die karthagische Politik und Strategie im 2. römisch-karthagischen Krieg erlaubt erst die Befreiung von der prorömischen, auf Hannibal fixierten Deutung der schriftlichen Quellen. Nicht nur er, sondern eine leistungsfähige Militärelite gestaltete unter Gesamtleitung der karthagischen Regierung die Kriegsführung. Deren strategische Prämisse war die Vermeidung eines Krieges auf afrikanischem Boden. Grundlage dafür waren Hannibals Erfolge in Italien, die Gewährleistung der Truppenversorgung sowie die Aktivierung und Gewinnung von Verbündeten. Dieses strategische Konzept geriet jedoch ins Wanken, in dem Maße als die Bündnisverpflichtungen Karthagos und die römischen Erfolge in Hispanien die karthagischen Ressourcen zu überfordern begannen. Das karthagische Kriegsziel eines Mächtegleichgewichts im westlichen Mittelmeerraum rückte in weite Ferne. Mit zunehmender Dauer des Krieges konnte Rom sein weit überlegenes strategisches und demographisches Potential ausspielen und schließlich in einen umfassenden Sieg ummünzen.
El stipendium, el cuestor y qui aes tribuebat (Gai. inst. IV 26). El abono de la paga al soldado en la República
Authors: Muñiz Coello J.
Published: October 2011

Las necesidades creadas por las guerras en los ejércitos romanos, englobadas dentro del alimento, vestido y paga militar, tres genéricas clases de gastos, fueron financiadas con la creación por el senado del tributum ex censu. Abordamos la fórmula de abono de esa paga, el aes militare del soldado, como responsabilidad del cuestor y sus delegados, además de los llamados tribuni aerarii. Sobre sus primitivas actividades hay parcas y confusas noticias en anticuarios y comentaristas romanos, como correspondía a una función ya obsoleta. De todoello nos ocupamos en este artículo.
Das griechische Vorbild der Strafdebatte in der sallustischen Coniuratio Catilinae
Authors: Gärtner Thomas
Published: October 2011

Die Frage nach der Quelle bzw. dem Vorbild der sallustischen Antilogie zwischen Caesar und Cato um die Bestrafung der Catilinarischen Verschwörer wird aufgeworfen: Nach der communis opinio folgt Sallust der thukydideischen Debatte um Mytilene, nach einer Hypothese von Willy Theiler dagegen einer bei Diodor (Bibliotheke XIII) überlieferten, teils auf Ephoros, teils auf Timaios zurückgeführten Antilogie. Es wird gezeigt, daß sowohl Sallust als auch die bei Diodor überlieferte Debatte auf Thukydides fußen, diesen jedoch in charakteristisch verschiedener Weise berücksichtigen.
Asinius Pollio in Dalmatia: What happened in Salona 39 BC?
Authors: Dzino Danijel
Published: October 2011

This paper re-examines the sources reporting on the campaigns of Asinius Pollio in 40/39 BC, and reviews the scholarly debate about the targets and aims of his campaigns. In the debate a new source is introduced, the passage on Pollio′s conquest of Salona, from the medieval Historia Salonitana of Thomas the Archdeacon of Spalatum (Split). The analysis shows that the passage from Thomas does not correspond with any known source and it suggests that he used a more substantial report on the siege and capture of Salona, probably from the textual tradition of the Vergilian scholia, which sprung from the lost commentary of Aelius Donatus. The existence of this textual tradition about Pollio′s campaign in central Dalmatia in the Vergilian scholia and the “Epitomes” of Florus, in conjunction with Horace′s mention of Pollio′ s Dalmatian triumph, makes it more certain that Pollio campaigned in central Dalmatia.
Germanische ,Gefolgschaften‘ und Germanicus-Horizont. Zur Aussagekraft des Leichenfundes im Halterner Töpferofen Nr. 10
Authors: Matijević Krešimir
Published: October 2011

Der außergewöhnliche Leichenfund im Ofen Nr. 10 vor dem Hauptlager von Haltern kann nun auch für die frühe römische Kaiserzeit germanische Kriegerverbände, die üblicherweise als ‘Gefolgschaften’ bezeichnet werden, archäologisch belegen. Die naturwissenschaftliche Analyse der Knochen zeigt, daß sich nicht nur Krieger verschiedener benachbarter Stämme für militärische Auseinandersetzungen zusammenfanden, sondern daß zu diesem Zwecke teilweise weite Wegstrecken zurückgelegt wurden.

Eine genaue Datierung der Deponierung der Leichen ist aus verschiedenen Gründen nicht möglich. Ein Zusammenhang mit den Ereignissen des Jahres 9 n. Chr. oder der folgenden Zeit kann somit nur vermutet werden.
Das Verständnis von Herrschaft in der anonymen Rede Eἰς βασιλέα (Ps.-Aelius Aristides): Ein Fürstenspiegel
Authors: Körner Christian
Published: October 2011

Die anonyme, im Corpus des Aelius Aristides überlieferte Rede Eἰς βασιλέα wird im folgenden Beitrag unter dem Aspekt des in ihr entwickelten Herrschaftsverständnisses analysiert und als Fürstenspiegel gedeutet. Die Rede schildert den Idealtypus des verantwortungsbewußten, besonnenen Herrschers, der seine Macht zum Wohle seiner Untertanen nutzt. Dabei wird weitgehend auf literarische Topoi zurückgegriffen, wie sie vor allem Isokrates und Xenophon entwickelt hatten und wie sie auch im rhetorischen Handbuch des Menander empfohlen wurden. Rätselhaft bleibt das völlige Fehlen individueller Hinweise auf den Adressaten der Rede.
Rule Britannia — zur Rolle Britanniens in der dynastischen Selbstdarstellung Theodosius des Großen
Authors: Olbrich Konstantin
Published: October 2011

Vor dem Hintergrund numismatischer Typentradition sowie einer spätrepublikanisch-kaiserzeitlichen Literatur, nach welcher Britannien neben Indien eine topisch herausgehobene Rolle für den römischen Weltherrschaftsanspruch zu spielen pflegte, erschließt sich aus Billonprägungen der östlichen Münzstätten der Beginn der dynastischen Propaganda Theodosius des Großen. Dieser ließ auf Maiorinen des Jahres 383 seinen wohl zeitgleich zum Staatsgott erhobenen Vater als Britannienfahrer darstellen. Dessen Siege auf der Insel scheinen als Hinweis auf die von der göttlichen Vorsehung bestimmte, künftige Herrschaft seiner Nachkommen propagiert worden zu sein. Deren Herrschaft wurde sodann durch das vertraute Mittel antiken Weltärendenkens zum Ergebnis göttlichen Wollens erklärt: Danach zeigte sich der Heilsplan der Gottheit darin, daß just nach Ablauf einer – zahlensymbolisch durch das Tau-Kreuz begründeten – Ära von 300 Jahren nach der ,endgültigen‘ Unterwerfung Britanniens durch Agricola im Jahr 83 der Enkel des Britanniensiegers Theodosius, Arcadius, 383 den Thron besteigen sollte. Die fehlende Übernahme der neuen östlichen Münzpropaganda durch Gratian bzw. ihre nur eingeschränkte Übernahme durch Valentinian II. im Westen zeigt, daß die damit vollzogene Dynastiegründung seitens des valentinianischen Kaiserhauses zurückgewiesen wurde. Magnus Maximus dürfte das daraus folgende, schwere Zerwürfnis zwischen West und Ost sowie die strittige Dynastiepropaganda seines angeblichen Verwandten Theodosius zur Umsetzung eigener Herrschaftspläne benutzt haben.
Interferometrische Messung von Freiform-Schneidkanten auf einer Diamantwerkzeugbearbeitungsmaschine
Authors: Berger Reinhard , Fleischle David , Körner Klaus , Lyda Wolfram , Osten Wolfgang , Sobotka Andreas , Wenzel Christian , Brecher Christian
Published: October 2011

Mit Diamantwerkzeugen lassen sich in einem Bearbeitungsschritt Oberflächen mit optischer Qualität erzeugen. Um insbesondere auch komplexe Oberflächenstrukturen mit einer reduzierten Anzahl an Zerspanungsabläufen fertigen zu können, sollen neue Werkzeuge mit Freiform-Schneidkanten zum Einsatz kommen. Voraussetzung sind jedoch Diamantwerkzeuge mit hoher Maßhaltigkeit, die bei ihrem Herstellungsprozess geprüft werden müssen. Hier werden sowohl das Konzept zur Prüfung dieser Freiform-Diamantwerkzeuge als auch die Ergebnisse eines simulierten messtechnischen Soll-Ist-Vergleichs vorgestellt.