bluuebunny/crossref_metadata_2025 huggingface dataset:
Associative Encoding and Retrieval Are Predicted by Functional Connectivity in Distinct Hippocampal Area CA1 Pathways
Authors: Duncan Katherine , Tompary Alexa , Davachi Lila
Published: September 2014

Determining how the hippocampus supports the unique demands of memory encoding and retrieval is fundamental for understanding the biological basis of episodic memory. One possibility proposed by theoretical models is that the distinct computational demands of encoding and retrieval are accommodated by shifts in the functional interaction between the hippocampal CA1 subregion and its input structures. However, empirical tests of this hypothesis are lacking. To test this in humans, we used high-resolution fMRI to measure functional connectivity between hippocampal area CA1 and regions of the medial temporal lobe and midbrain during extended blocks of associative encoding and retrieval tasks. We found evidence for a double dissociation between the pathways supporting successful encoding and retrieval. Specifically, during the associative encoding task, but not the retrieval task, functional connectivity only between area CA1 and the ventral tegmental area predicted associative long-term memory. In contrast, connectivity between area CA1 and DG/CA3 was greater, on average, during the retrieval task compared with the encoding task, and, importantly, the strength of this connectivity significantly correlated with retrieval success. Together, these findings serve as an important first step toward understanding how the demands of fundamental memory processes may be met by changes in the relative strength of connectivity within hippocampal pathways.
Plasticity of Binocularity and Visual Acuity Are Differentially Limited by Nogo Receptor
Authors: Stephany Céleste-Élise , Chan Leanne L.H. , Parivash Sherveen N. , Dorton Hilary M. , Piechowicz Mariel , Qiu Shenfeng , McGee Aaron W.
Published: September 2014

The closure of developmental critical periods consolidates neural circuitry but also limits recovery from early abnormal sensory experience. Degrading vision by one eye throughout a critical period both perturbs ocular dominance (OD) in primary visual cortex and impairs visual acuity permanently. Yet understanding how binocularity and visual acuity interrelate has proven elusive. Here we demonstrate the plasticity of binocularity and acuity are separable and differentially regulated by the neuronal nogo receptor 1 (NgR1). Mice lacking NgR1 display developmental OD plasticity as adults and their visual acuity spontaneously improves after prolonged monocular deprivation. Restricting deletion of NgR1 to either cortical interneurons or a subclass of parvalbumin (PV)-positive interneurons alters intralaminar synaptic connectivity in visual cortex and prevents closure of the critical period for OD plasticity. However, loss of NgR1 in PV neurons does not rescue deficits in acuity induced by chronic visual deprivation. Thus, NgR1 functions with PV interneurons to limit plasticity of binocularity, but its expression is required more extensively within brain circuitry to limit improvement of visual acuity following chronic deprivation.
mGlu1 Receptor-Induced LTD of NMDA Receptor Transmission Selectively at Schaffer Collateral-CA1 Synapses Mediates Metaplasticity
Authors: Bhouri Mehdi , Farrow Paul A. , Motee Aneeta , Yan Xu , Battaglia Giuseppe , Di Menna Luisa , Riozzi Barbara , Nicoletti Ferdinando , Fitzjohn Stephen M. , Bashir Zafar I.
Published: September 2014

Hippocampal CA1 pyramidal neurons receive inputs from entorhinal cortex directly via the temporoammonic (TA) pathway and indirectly via the Schaffer collateral (SC) pathway from CA3. NMDARs at synapses of both pathways are critical for the induction of synaptic plasticity, information processing, and learning and memory. We now demonstrate that, in the rat hippocampus, activity-dependent mGlu1 receptor-mediated LTD (mGlu1-LTD) of NMDAR-mediated transmission (EPSCNMDA) at the SC-CA1 input prevents subsequent LTP of AMPAR-mediated transmission. In contrast, there was no activity-dependent mGlu1-LTD of EPSCNMDAat the TA-CA1 pathway, or effects on subsequent plasticity of AMPAR-mediated transmission. Therefore, the two major pathways delivering information to CA1 pyramidal neurons are subject to very different plasticity rules.
Inhibition of Adenylyl Cyclase Type 5 Prevents l-DOPA-Induced Dyskinesia in an Animal Model of Parkinson's Disease
Authors: Park Hye-Yeon , Kang Young-Mi , Kang Young , Park Tae-Shin , Ryu Young-Kyoung , Hwang Jung-Hwan , Kim Yong-Hoon , Chung Bong-Hyun , Nam Ki-Hoan , Kim Mee-Ree , Lee Chul-Ho , Han Pyung-Lim , Kim Kyoung-Shim
Published: September 2014

The dopamine precursorl-3,4-dihydroxyphenylalanine (l-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use ofl-DOPA leads to the development of debilitating involuntary movements, calledl-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment withl-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment withl-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/ΔFosB expression, which was induced by long-terml-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease.
Mechanisms of Sharp Wave Initiation and Ripple Generation
Authors: Schlingloff Dániel , Káli Szabolcs , Freund Tamás F. , Hájos Norbert , Gulyás Attila I.
Published: September 2014

Replay of neuronal activity during hippocampal sharp wave-ripples (SWRs) is essential in memory formation. To understand the mechanisms underlying the initiation of irregularly occurring SWRs and the generation of periodic ripples, we selectively manipulated different components of the CA3 network in mouse hippocampal slices. We recorded EPSCs and IPSCs to examine the buildup of neuronal activity preceding SWRs and analyzed the distribution of time intervals between subsequent SWR events. Our results suggest that SWRs are initiated through a combined refractory and stochastic mechanism. SWRs initiate when firing in a set of spontaneously active pyramidal cells triggers a gradual, exponential buildup of activity in the recurrent CA3 network. We showed that this tonic excitatory envelope drives reciprocally connected parvalbumin-positive basket cells, which start ripple-frequency spiking that is phase-locked through reciprocal inhibition. The synchronized GABAAreceptor-mediated currents give rise to a major component of the ripple-frequency oscillation in the local field potential and organize the phase-locked spiking of pyramidal cells. Optogenetic stimulation of parvalbumin-positive cells evoked full SWRs and EPSC sequences in pyramidal cells. Even with excitation blocked, tonic driving of parvalbumin-positive cells evoked ripple oscillations. Conversely, optogenetic silencing of parvalbumin-positive cells interrupted the SWRs or inhibited their occurrence. Local drug applications and modeling experiments confirmed that the activity of parvalbumin-positive perisomatic inhibitory neurons is both necessary and sufficient for ripple-frequency current and rhythm generation. These interneurons are thus essential in organizing pyramidal cell activity not only during gamma oscillation, but, in a different configuration, during SWRs.
Within-Hemifield Competition in Early Visual Areas Limits the Ability to Track Multiple Objects with Attention
Authors: Störmer Viola S. , Alvarez George A. , Cavanagh Patrick
Published: September 2014

It is much easier to divide attention across the left and right visual hemifields than within the same visual hemifield. Here we investigate whether this benefit of dividing attention across separate visual fields is evident at early cortical processing stages. We measured the steady-state visual evoked potential, an oscillatory response of the visual cortex elicited by flickering stimuli, of moving targets and distractors while human observers performed a tracking task. The amplitude of responses at the target frequencies was larger than that of the distractor frequencies when participants tracked two targets in separate hemifields, indicating that attention can modulate early visual processing when it is divided across hemifields. However, these attentional modulations disappeared when both targets were tracked within the same hemifield. These effects were not due to differences in task performance, because accuracy was matched across the tracking conditions by adjusting target speed (with control conditions ruling out effects due to speed alone). To investigate later processing stages, we examined the P3 component over central-parietal scalp sites that was elicited by the test probe at the end of the trial. The P3 amplitude was larger for probes on targets than on distractors, regardless of whether attention was divided across or within a hemifield, indicating that these higher-level processes were not constrained by visual hemifield. These results suggest that modulating early processing stages enables more efficient target tracking, and that within-hemifield competition limits the ability to modulate multiple target representations within the hemifield maps of the early visual cortex.
Optimal Combination of Neural Temporal Envelope and Fine Structure Cues to Explain Speech Identification in Background Noise
Authors: Moon Il Joon , Won Jong Ho , Park Min-Hyun , Ives D. Timothy , Nie Kaibao , Heinz Michael G. , Lorenzi Christian , Rubinstein Jay T.
Published: September 2014

The dichotomy between acoustic temporal envelope (ENV) and fine structure (TFS) cues has stimulated numerous studies over the past decade to understand the relative role of acoustic ENV and TFS in human speech perception. Such acoustic temporal speech cues produce distinct neural discharge patterns at the level of the auditory nerve, yet little is known about the central neural mechanisms underlying the dichotomy in speech perception between neural ENV and TFS cues. We explored the question of how the peripheral auditory system encodes neural ENV and TFS cues in steady or fluctuating background noise, and how the central auditory system combines these forms of neural information for speech identification. We sought to address this question by (1) measuring sentence identification in background noise for human subjects as a function of the degree of available acoustic TFS information and (2) examining the optimal combination of neural ENV and TFS cues to explain human speech perception performance using computational models of the peripheral auditory system and central neural observers. Speech-identification performance by human subjects decreased as the acoustic TFS information was degraded in the speech signals. The model predictions best matched human performance when a greater emphasis was placed on neural ENV coding rather than neural TFS. However, neural TFS cues were necessary to account for the full effect of background-noise modulations on human speech-identification performance.
Benefits of Pathway Splitting in Sensory Coding
Authors: Gjorgjieva Julijana , Sompolinsky Haim , Meister Markus
Published: September 2014

In many sensory systems, the neural signal splits into multiple parallel pathways. For example, in the mammalian retina, ∼20 types of retinal ganglion cells transmit information about the visual scene to the brain. The purpose of this profuse and early pathway splitting remains unknown. We examine a common instance of splitting into ON and OFF neurons excited by increments and decrements of light intensity in the visual scene, respectively. We test the hypothesis that pathway splitting enables more efficient encoding of sensory stimuli. Specifically, we compare a model system with an ON and an OFF neuron to one with two ON neurons. Surprisingly, the optimal ON–OFF system transmits the same information as the optimal ON–ON system, if one constrains the maximal firing rate of the neurons. However, the ON–OFF system uses fewer spikes on average to transmit this information. This superiority of the ON–OFF system is also observed when the two systems are optimized while constraining their mean firing rate. The efficiency gain for the ON–OFF split is comparable with that derived from decorrelation, a well known processing strategy of early sensory systems. The gain can be orders of magnitude larger when the ecologically important stimuli are rare but large events of either polarity. The ON–OFF system also provides a better code for extracting information by a linear downstream decoder. The results suggest that the evolution of ON–OFF diversification in sensory systems may be driven by the benefits of lowering average metabolic cost, especially in a world in which the relevant stimuli are sparse.
Anterior Insula Activity Reflects the Effects of Intentionality on the Anticipation of Aversive Stimulation
Authors: Liljeholm Mimi , Dunne Simon , O'Doherty John P.
Published: September 2014

If someone causes you harm, your affective reaction to that person might be profoundly influenced by your inferences about the intentionality of their actions. In the present study, we aimed to understand how affective responses to a biologically salient aversive outcome administered by others are modulated by the extent to which a given individual is judged to have deliberately or inadvertently delivered the outcome. Using fMRI, we examined how neural responses to anticipation and receipt of an aversive stimulus are modulated by this fundamental social judgment. We found that affective evaluations about an individual whose actions led to either noxious or neutral consequences for the subject did indeed depend on the perceived intentions of that individual. At the neural level, activity in the anterior insula correlated with the interaction between perceived intentionality and anticipated outcome valence, suggesting that this region reflects the influence of mental state attribution on aversive expectations
A Class of GABAergic Neurons in the Prefrontal Cortex Sends Long-Range Projections to the Nucleus Accumbens and Elicits Acute Avoidance Behavior
Authors: Lee Anthony T. , Vogt Daniel , Rubenstein John L. , Sohal Vikaas S.
Published: September 2014

GABAergic projections from the neocortex to subcortical structures have been poorly characterized. UsingDlxi12b–Cremice, we found anatomical evidence for GABAergic neurons that project from the mouse medial prefrontal cortex (mPFC) to multiple subcortical targets. We used a combination of patch-clamp electrophysiology, optogenetics, and pharmacology to confirm that Dlxi12b-labeled projections from the mPFC to the nucleus accumbens (NAcc) release GABA and do not corelease glutamate. Furthermore, optogenetic stimulation of these GABAergic projections from mPFC to NAcc induces avoidance behavior in a real-time place preference task, suggesting that these long-range projecting GABAergic neurons can transmit aversive signals. Finally, we found evidence for heterogeneous histochemical and/or electrophysiological properties of long-range projecting GABAergic neurons in the mPFC. Some of these neurons were labeled inparvalbumin–Creandvasoactive intestinal peptide–Cremice. We also used a novel intersectional targeting strategy to label GABAergic neurons in the mPFC that project to NAcc and found that these neurons have fast-spiking properties and express parvalbumin. These results define possible functions and properties for a class of long-range projecting GABAergic neurons in the neocortex.
Phasic Dopaminergic Activity Exerts Fast Control of Cholinergic Interneuron Firing via Sequential NMDA, D2, and D1 Receptor Activation
Authors: Wieland Sebastian , Du Dan , Oswald Manfred J. , Parlato Rosanna , Köhr Georg , Kelsch Wolfgang
Published: September 2014

Phasic increases in dopamine (DA) are involved in the detection and selection of relevant sensory stimuli. The DAergic and cholinergic system dynamically interact to gate and potentiate sensory inputs to striatum. Striatal cholinergic interneurons (CINs) respond to relevant sensory stimuli with an initial burst, a firing pause, or a late burst, or a combination of these three components. CIN responses coincide with phasic firing of DAergic neuronsin vivo. In particular, the late burst of CINs codes for the anticipated reward. To examine whether DAergic midbrain afferents can evoke the different CIN responses, we recorded from adult olfactory tubercle slices in the mouse ventral striatum. Olfactory inputs to striatal projection neurons were gated by the cholinergic tone. Phasic optogenetic activation of DAergic terminals evoked combinations of initial bursts, pauses, and late bursts in subsets of CINs by distinct receptor pathways. Glutamate release from midbrain afferents evoked an NMDAR-dependent initial burst followed by an afterhyperpolarization-induced pause. Phasic release of DA itself evoked acute changes in CIN firing. In particular, in CINs without an initial burst, phasic DA release evoked a pause through D2-type DA receptor activation. Independently, phasic DA activated a slow depolarizing conductance and the late burst through a D1-type DA receptor pathway. In summary, DAergic neurons elicit transient subsecond firing responses in CINs by sequential activation of NMDA, D2-type, and D1-type receptors. This fast control of striatal cholinergic tone by phasic DA provides a novel dynamic link of two transmitter systems central to the detection and selection of relevant stimuli.
TACE/ADAM17 Is Essential for Oligodendrocyte Development and CNS Myelination
Authors: Palazuelos Javier , Crawford Howard C. , Klingener Michael , Sun Bingru , Karelis Jason , Raines Elaine W. , Aguirre Adan
Published: September 2014

Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPsin vivoleads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination.
Nerve Growth Factor Sensitizes Adult Sympathetic Neurons to the Proinflammatory Peptide Bradykinin
Authors: Vivas Oscar , Kruse Martin , Hille Bertil
Published: September 2014

Levels of nerve growth factor (NGF) are elevated in inflamed tissues. In sensory neurons, increases in NGF augment neuronal sensitivity (sensitization) to noxious stimuli. Here, we hypothesized that NGF also sensitizes sympathetic neurons to proinflammatory stimuli. We cultured superior cervical ganglion (SCG) neurons from adult male Sprague Dawley rats with or without added NGF and compared their responsiveness to bradykinin, a proinflammatory peptide. The NGF-cultured neurons exhibited significant depolarization, bursts of action potentials, and Ca2+elevations after bradykinin application, whereas neurons cultured without NGF showed only slight changes in membrane potential and cytoplasmic Ca2+levels. The NGF effect, which requires trkA receptors, takes hours to develop and days to reverse. We addressed the ionic mechanisms underlying this sensitization. NGF did not alter bradykinin-induced M-current inhibition or phosphatidylinositol 4,5-bisphosphate hydrolysis. Maxi-K channel-mediated current evoked by depolarizations was reduced by 50% by culturing neurons in NGF. Application of iberiotoxin or paxilline, blockers of Maxi-K channels, mimicked NGF treatment and sensitized neurons to bradykinin application. A calcium channel blocker also mimicked NGF treatment. We found that NGF reduces Maxi-K channel opening by decreasing the activity of nifedipine-sensitive calcium channels. In conclusion, culture in NGF reduces the activity of L-type calcium channels, and secondarily, the calcium-sensitive activity of Maxi-K channels, rendering sympathetic neurons electrically hyper-responsive to bradykinin.
Deletion of Prostaglandin E2Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever
Authors: Wilhelms Daniel Björk , Kirilov Milen , Mirrasekhian Elahe , Eskilsson Anna , Kugelberg Unn Örtegren , Klar Christine , Ridder Dirk A. , Herschman Harvey R. , Schwaninger Markus , Blomqvist Anders , Engblom David
Published: September 2014

Fever is a hallmark of inflammatory and infectious diseases. The febrile response is triggered by prostaglandin E2synthesis mediated by induced expression of the enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1). The cellular source for pyrogenic PGE2remains a subject of debate; several hypotheses have been forwarded, including immune cells in the periphery and in the brain, as well as the brain endothelium. Here we generated mice with selective deletion of COX-2 and mPGES1 in brain endothelial cells. These mice displayed strongly attenuated febrile responses to peripheral immune challenge. In contrast, inflammation-induced hypoactivity was unaffected, demonstrating the physiological selectivity of the response to the targeted gene deletions. These findings demonstrate that PGE2synthesis in brain endothelial cells is critical for inflammation-induced fever.
An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Authors: Zhang Ye , Chen Kenian , Sloan Steven A. , Bennett Mariko L. , Scholze Anja R. , O'Keeffe Sean , Phatnani Hemali P. , Guarnieri Paolo , Caneda Christine , Ruderisch Nadine , Deng Shuyun , Liddelow Shane A. , Zhang Chaolin , Daneman Richard , Maniatis Tom , Barres Ben A. , Wu Jia Qian
Published: September 2014

The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing ofPKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain.
Engrailed Alters the Specificity of Synaptic Connections ofDrosophilaAuditory Neurons with the Giant Fiber
Authors: Pézier Adeline , Jezzini Sami H. , Marie Bruno , Blagburn Jonathan M.
Published: September 2014

We show that a subset of sound-detecting Johnston's Organ neurons (JONs) inDrosophila melanogaster, which express the transcription factors Engrailed (En) and Invected (Inv), form mixed electrical and chemical synaptic inputs onto the giant fiber (GF) dendrite. These synaptic connections are detected by trans-synaptic Neurobiotin (NB) transfer and by colocalization of Bruchpilot-short puncta. We then show that misexpressing En postmitotically in a second subset of sound-responsive JONs causes them to form ectopic electrical and chemical synapses with the GF, in turn causing that postsynaptic neuron to redistribute its dendritic branches into the vicinity of these afferents. We also introduce a simple electrophysiological recording paradigm for quantifying the presynaptic and postsynaptic electrical activity at this synapse, by measuring the extracellular sound-evoked potentials (SEPs) from the antennal nerve while monitoring the likelihood of the GF firing an action potential in response to simultaneous subthreshold sound and voltage stimuli. Ectopic presynaptic expression of En strengthens the synaptic connection, consistent with there being more synaptic contacts formed. Finally, RNAi-mediated knockdown of En and Inv in postmitotic neurons reduces SEP amplitude but also reduces synaptic strength at the JON–GF synapse. Overall, these results suggest that En and Inv in JONs regulate both neuronal excitability and synaptic connectivity.
Regulation of Blood Flow in the Retinal Trilaminar Vascular Network
Authors: Kornfield Tess E. , Newman Eric A.
Published: September 2014

Light stimulation evokes neuronal activity in the retina, resulting in the dilation of retinal blood vessels and increased blood flow. This response, named functional hyperemia, brings oxygen and nutrients to active neurons. However, it remains unclear which vessels mediate functional hyperemia. We have characterized blood flow regulation in the rat retinain vivoby measuring changes in retinal vessel diameter and red blood cell (RBC) flux evoked by a flickering light stimulus. We found that, in first- and second-order arterioles, flicker evoked large (7.5 and 5.0%), rapid (0.73 and 0.70 s), and consistent dilations. Flicker-evoked dilations in capillaries were smaller (2.0%) and tended to have a slower onset (0.97 s), whereas dilations in venules were smaller (1.0%) and slower (1.06 s) still. The proximity of pericyte somata did not predict capillary dilation amplitude. Expression of the contractile protein α-smooth muscle actin was high in arterioles and low in capillaries. Unexpectedly, we found that blood flow in the three vascular layers was differentially regulated. Flicker stimulation evoked far larger dilations and RBC flux increases in the intermediate layer capillaries than in the superficial and deep layer capillaries (2.6 vs 0.9 and 0.7% dilation; 25.7 vs 0.8 and 11.3% RBC flux increase). These results indicate that functional hyperemia in the retina is driven primarily by active dilation of arterioles. The dilation of intermediate layer capillaries is likely mediated by active mechanisms as well. The physiological consequences of differential regulation in the three vascular layers are discussed.
Dynamic Representation of the Temporal and Sequential Structure of Rhythmic Movements in the Primate Medial Premotor Cortex
Authors: Crowe David A. , Zarco Wilbert , Bartolo Ramon , Merchant Hugo
Published: September 2014

We determined the encoding properties of single cells and the decoding accuracy of cell populations in the medial premotor cortex (MPC) of Rhesus monkeys to represent in a time-varying fashion the duration and serial order of six intervals produced rhythmically during a synchronization-continuation tapping task. We found that MPC represented the temporal and sequential structure of rhythmic movements by activating small ensembles of neurons that encoded the duration or the serial order in rapid succession, so that the pattern of active neurons changed dramatically within each interval. Interestingly, the width of the encoding or decoding function for serial order increased as a function of duration. Finally, we found that the strength of correlation in spontaneous activity of the individual cells varied as a function of the timing of their recruitment. These results demonstrate the existence of dynamic representations in MPC for the duration and serial order of intervals produced rhythmically and suggest that this dynamic code depends on ensembles of interconnected neurons that provide a strong synaptic drive to the next ensemble in a consecutive chain of neural events.
Near-Optimal Decoding of Transient Stimuli from Coupled Neuronal Subpopulations
Authors: Trousdale James , Carroll Samuel R. , Gabbiani Fabrizio , Josić Krešimir
Published: September 2014

Coupling between sensory neurons impacts their tuning properties and correlations in their responses. How such coupling affects sensory representations and ultimately behavior remains unclear. We investigated the role of neuronal coupling during visual processing using a realistic biophysical model of the vertical system (VS) cell network in the blow fly. These neurons are thought to encode the horizontal rotation axis during rapid free-flight maneuvers. Experimental findings suggest that neurons of the VS are strongly electrically coupled, and that several downstream neurons driving motor responses to ego-rotation receive inputs primarily from a small subset of VS cells. These downstream neurons must decode information about the axis of rotation from a partial readout of the VS population response. To investigate the role of coupling, we simulated the VS response to a variety of rotating visual scenes and computed optimal Bayesian estimates from the relevant subset of VS cells. Our analysis shows that coupling leads to near-optimal estimates from a subpopulation readout. In contrast, coupling between VS cells has no impact on the quality of encoding in the response of the full population. We conclude that coupling at one level of the fly visual system allows for near-optimal decoding from partial information at the subsequent, premotor level. Thus, electrical coupling may provide a general mechanism to achieve near-optimal information transfer from neuronal subpopulations across organisms and modalities.
Motor Variability Arises from a Slow Random Walk in Neural State
Authors: Chaisanguanthum Kris S. , Shen Helen H. , Sabes Philip N.
Published: September 2014

Even well practiced movements cannot be repeated without variability. This variability is thought to reflect “noise” in movement preparation or execution. However, we show that, for both professional baseball pitchers and macaque monkeys making reaching movements, motor variability can be decomposed into two statistical components, a slowly drifting mean and fast trial-by-trial fluctuations about the mean. The preparatory activity of dorsal premotor cortex/primary motor cortex neurons in monkey exhibits similar statistics. Although the neural and behavioral drifts appear to be correlated, neural activity does not account for trial-by-trial fluctuations in movement, which must arise elsewhere, likely downstream. The statistics of this drift are well modeled by a double-exponential autocorrelation function, with time constants similar across the neural and behavioral drifts in two monkeys, as well as the drifts observed in baseball pitching. These time constants can be explained by an error-corrective learning processes and agree with learning rates measured directly in previous experiments. Together, these results suggest that the central contributions to movement variability are not simply trial-by-trial fluctuations but are rather the result of longer-timescale processes that may arise from motor learning.
MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling
Authors: Dixon-Salazar Tracy J. , Fourgeaud Lawrence , Tyler Carolyn M. , Poole Julianna R. , Park Joseph J. , Boulanger Lisa M.
Published: September 2014

Proteins of the major histocompatibility complex class I (MHCI) negatively regulate synapse density in the developing vertebrate brain (Glynn et al., 2011; Elmer et al., 2013; Lee et al., 2014), but the underlying mechanisms remain largely unknown. Here we identify a novel MHCI signaling pathway that involves the inhibition of a known synapse-promoting factor, the insulin receptor. Dominant-negative insulin receptor constructs decrease synapse density in the developingXenopusvisual system (Chiu et al., 2008), and insulin receptor activation increases dendritic spine density in mouse hippocampal neuronsin vitro(Lee et al., 2011). We find that genetically reducing cell surface MHCI levels increases synapse density selectively in regions of the hippocampus where insulin receptors are expressed, and occludes the neuronal insulin response by de-repressing insulin receptor signaling. Pharmacologically inhibiting insulin receptor signaling in MHCI-deficient animals rescues synapse density, identifying insulin receptor signaling as a critical mediator of the tonic inhibitory effects of endogenous MHCI on synapse number. Insulin receptors co-immunoprecipitate MHCI from hippocampal lysates, and MHCI unmasks a cytoplasmic epitope of the insulin receptor that mediates downstream signaling. These results identify an important role for an MHCI–insulin receptor signaling pathway in circuit patterning in the developing brain, and suggest that changes in MHCI expression could unexpectedly regulate neuronal insulin sensitivity in the aging and diseased brain.
Intersubject Variability of and Genetic Effects on the Brain's Functional Connectivity during Infancy
Authors: Gao Wei , Elton Amanda , Zhu Hongtu , Alcauter Sarael , Smith J. Keith , Gilmore John H. , Lin Weili
Published: September 2014

Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brain's functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brain's functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brain's functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy.
Bmal1Is an Essential Regulator for Circadian Cytosolic Ca2+Rhythms in Suprachiasmatic Nucleus Neurons
Authors: Ikeda Masayuki , Ikeda Masaaki
Published: September 2014

The hypothalamic suprachiasmatic nucleus (SCN) plays a pivotal role in the mammalian circadian clock system.Bmal1is a clock gene that drives transcriptional-translational feedback loops (TTFLs) for itself and other genes, and is expressed in nearly all SCN neurons. Despite strong evidence thatBmal1-null mutant mice display arrhythmic behavior under constant darkness, the function ofBmal1in neuronal activity is unknown. Recently, periodic changes in the levels of intracellular signaling messengers, such as cytosolic Ca2+and cAMP, were suggested to regulate TTFLs. However, the opposite aspect of how clock gene TTFLs regulate cytosolic signaling remains unclear. To investigate intracellular Ca2+dynamics underBmal1perturbations, we cotransfected some SCN neurons withyellow cameleontogether with wild-type or dominant-negativeBmal1using a gene-gun applied for mouse organotypic cultures. Immunofluorescence staining for a tag protein linked to BMAL1 showed nuclear expression of wild-type BMAL1 and its degradation within 1 week after transfection in SCN neurons. However, dominant-negative BMAL1 did not translocate into the nucleus and the cytosolic signals persisted beyond 1 week. Consistently, circadian Ca2+rhythms in SCN neurons were inhibited for longer periods by dominant-negativeBmal1overexpression. Furthermore, SCN neurons transfected with aBmal1shRNA lengthened, whereas those overexpressing wild-typeBmal1shortened, the periods of Ca2+rhythms, with a significant reduction in their amplitude. BMAL1 expression was intact in the majority of neighboring neurons in organotypic cultures. Therefore, we conclude that proper intrinsicBmal1expression, but not passive signaling via cell-to-cell interactions, is the determinant of circadian Ca2+rhythms in SCN neurons.
De Novo Transcriptome Sequence Assembly from Coconut Leaves and Seeds with a Focus on Factors Involved in RNA-Directed DNA Methylation
Authors: Huang Ya-Yi , Lee Chueh-Pai , Fu Jason L , Chang Bill Chia-Han , Matzke Antonius J M , Matzke Marjori
Published: September 2014

Coconut palm (Cocos nucifera) is a symbol of the tropics and a source of numerous edible and nonedible products of economic value. Despite its nutritional and industrial significance, coconut remains under-represented in public repositories for genomic and transcriptomic data. We report de novo transcript assembly from RNA-seq data and analysis of gene expression in seed tissues (embryo and endosperm) and leaves of a dwarf coconut variety. Assembly of 10 GB sequencing data for each tissue resulted in 58,211 total unigenes in embryo, 61,152 in endosperm, and 33,446 in leaf. Within each unigene pool, 24,857 could be annotated in embryo, 29,731 could be annotated in endosperm, and 26,064 could be annotated in leaf. A KEGG analysis identified 138, 138, and 139 pathways, respectively, in transcriptomes of embryo, endosperm, and leaf tissues. Given the extraordinarily large size of coconut seeds and the importance of small RNA-mediated epigenetic regulation during seed development in model plants, we used homology searches to identify putative homologs of factors required for RNA-directed DNA methylation in coconut. The findings suggest that RNA-directed DNA methylation is important during coconut seed development, particularly in maturing endosperm. This dataset will expand the genomics resources available for coconut and provide a foundation for more detailed analyses that may assist molecular breeding strategies aimed at improving this major tropical crop.
Defects and Diffusion in Amorphous Alloys
Authors: Averback R.S.
Published: September 2014

Since 1959 when P. Duwez showed at Caltech that Au-Si alloys could be quenched into a glassy state, there has been much interest in elucidating the nature of these amorphous materials. Certainly part of the motivation for studying amorphous alloys derives from their potential technological value: they are characterized by high hardness, corrosion and oxidation resistance, and high magnetic permeabilites and electrical resistivities but an equally strong motivation is simply that they are interesting materials. Scientific curiosity is stimulated by such fundamental questions as: What is their structure? Can defects be defined within this structure? What are the possible mechanisms of atomic transport? In addition, amorphous alloys provide a paradigm of a dense metastable structure, and how atomic transport can take place in such systems without transforming to more stable configurations is not well understood. Yet, as materials formed by nonequilibrium processing, e.g., nanocrystals, superlattices, rapidly solidified and ion-beam-modified materials, etc., find their way into technology, this question becomes increasingly germane. Ironically, much of the renewed interest in diffusion in amorphous alloys has been stimulated by the discovery, also at Caltech, of the solid-state amorphizing reaction, where multilayers of crystalline metal films transform to amorphous alloys by solid-state diffusion, rather than vice versa.
Modelo Europeu de Satisfação: um estudo de caso com discentes de uma Instituição de Ensino Superior
Authors: Cavalheiro Everton Anger , Tavares Carlos Eduardo Moreira , Ferreira Ana Paula Alf Lima , Santos Rozali Araujo dos , Stedile Cristiano da Silva de Mello
Published: September 2014

A presente pesquisa teve como objetivo avaliar os determinantes da satisfação geral do corpo discentes de uma instituição de ensino superior do noroeste do Rio Grande do Sul. Para tanto, realizou-se uma pesquisa quantitativa descritiva, a qual se utilizou de um modelo baseado em uma Survey, com 402 discentes, sendo que o instrumento utilizado para realização da pesquisa baseou-se no modelo europeu de satisfação. Representado por uma equação estrutural (PASWAN YOUNG, 2002, apud VIEIRA et al., 2008), o ECSI (Modelo Europeu de Satisfação) tem como foco: (I) avaliar a influência da qualidade percebida, da expectativa de qualidade, da imagem e do valor percebido na satisfação geral dos alunos; (II) avaliar a influência da satisfação geral dos alunos no nível de lealdade e de retenção dos alunos na instituição de ensino, e (III) apontar áreas chaves bem como de mensurar um conjunto de indicadores para a gestão da satisfação e manutenção dos alunos da instituição em análise. Desta forma, com a aplicação do referido instrumento, encontraram-se três fatores capazes de explicar 78% da satisfação do aluno perante a universidade: o primeiro e mais representativo fator foi chamado de valor percebido pelo aluno, que se trata do valor ou nível percebido da qualidade do ensino pelo preço pago pelos alunos, o segundo fator trata-se da imagem da universidade e o terceiro fator trata-se das expectativas do aluno. Palavras-chave: Satisfação. Modelo Europeu. Discentes. ECSI.
Uso de produtos eletrodomésticos por idosos: adequação das informações
Authors: Oliveira Luciana Aparecida de , Bifano Amélia Carla Sobrinho
Published: September 2014

Este estudo buscou avaliar a adequação das informações disponibilizadas por manuais de instruções de forno micro-ondas às normas, o nível de compreensão destas por usuários idosos em relação ao uso seguro do produto. Os procedimentos utilizados foram a análise das informações de cinco manuais de fornos micro-ondas de marcas distintas por meio dos critérios preconizados pelas normas: ISOGUIDE 37 e ISO 2145 e seleção de termos e palavras que geraram dúvidas nessa avaliação para averiguação do entendimento destes pelos idosos. Os manuais foram analisados a partir dos itens elencados das normas que estariam adequados ao produto em avaliação, a adequação das informações foram avaliadas em “atende”, “não atende” e “atende parcialmente”. Os resultados indicam que os manuais de instruções dos fornos micro-ondas apresentam não conformidade em relação a: estrutura do manual, estrutura da escrita, legibilidade e princípios gerais. Em relação ao significado dos termos e palavras, os resultados mostraram diferenças entre os significados impressos pelos fabricantes e o que os usuários entendem. A falta de atenção às normas e de conhecimento sobre os usuários dos produtos, levaram a manuais com erros gramaticais, títulos em índice diferente do utilizado no manual, uso de termos complexos e palavras em inglês, tamanho de letra pequena, textos extensos, inconsistência entre as informações contidas manual e no produto, dentre outros. Palavras-chave: Normas ISOs. Manuais de Instruções. Produtos.
Estudo de internacionalização de franquias brasileiras: desafios e barreiras
Authors: Leite Helena Loffredo da Rocha , Mendonça Paulo Sérgio Miranda , Buzzo Everton José
Published: September 2014

Este estudo objetivou analisar a internacionalização de franquias brasileiras através de um estudo de caso, buscando identificar fatores que influenciaram a internacionalização, as adaptações das estratégias de marketing e as principais barreiras e desafios da internacionalização de franquias brasileiras. Foi realizada uma pesquisa exploratória qualitativa através do método de estudo de caso. As informações foram coletadas através de observação e entrevistas semiestruturadas com os gestores responsáveis pela expansão internacional de duas empresas. A análise dos resultados ocorreu através de comparação entre as informações obtidas e o referencial teórico. Os resultados demonstraram que as empresas estudadas expandiram-se internacionalmente devido as demandas externas e ao desejo de explorar novos mercados. São realizadas mudanças nas estratégias de marketing em diferentes graus, sendo a comunicação o elemento mais alterado. O principal desafio à internacionalização encontrado foi compreender a cultura local e incorporá-la à operação. Palavras-chave: Franquias. Internacionalização. Estratégia de Marketing.
Redes de inovação: mapeamento de inventores de patentes em uma empresa do setor de cosméticos
Authors: Serrano Bruno Pinto , Gobbo Junior José Alcides
Published: September 2014

Este artigo tem o objetivo de identificar padrões na organização da rede de inovação, através de mapeamentos de redes de inventores de uma empresa de cosméticos, além de identificar formas de promover a capacidade de inovação por meio da interconectividade. A execução da pesquisa foi realizada por meio de métodos de estudo de casos, e, para isso, foram feitos mapeamentos de inventores, com base nos registros de patentes pesquisados previamente, levando-se em consideração o vínculo (interno ou externo) com a empresa de cada inventor e também a quantidade de citações da patente. Foi identificada maior hierarquia nas redes com a presença de colaboradores externos à empresa, bem como um possível maior teor tecnológico, já que a quantidade de citações foi superior às de outras redes. Verifica-se, por fim, que um mapeamento de inventores (apesar de patente não ser o único fator de medida de inovação) pode identificar características importantes para auxiliar uma melhor gestão da inovação. Palavras-chave: Inovação. Redes de Inovação. Análise de Redes.