bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast Learning with Weak Synaptic Plasticity
Authors: Yger Pierre , Stimberg Marcel , Brette Romain 
Published: September 2015

New sensory stimuli can be learned with a single or a few presentations. Similarly, the responses of cortical neurons to a stimulus have been shown to increase reliably after just a few repetitions. Long-term memory is thought to be mediated by synaptic plasticity, butin vitroexperiments in cortical cells typically show very small changes in synaptic strength after a pair of presynaptic and postsynaptic spikes. Thus, it is traditionally thought that fast learning requires stronger synaptic changes, possibly because of neuromodulation. Here we show theoretically that weak synaptic plasticity can, in fact, support fast learning, because of the large number of synapsesNonto a cortical neuron. In the fluctuation-driven regime characteristic of cortical neuronsin vivo, the size of membrane potential fluctuations grows only asN, whereas a single output spike leads to potentiation of a number of synapses proportional toN.Therefore, the relative effect of a single spike on synaptic potentiation grows asN. This leverage effect requires precise spike timing. Thus, the large number of synapses onto cortical neurons allows fast learning with very small synaptic changes.SIGNIFICANCE STATEMENTLong-term memory is thought to rely on the strengthening of coactive synapses. This physiological mechanism is generally considered to be very gradual, and yet new sensory stimuli can be learned with just a few presentations. Here we show theoretically that this apparent paradox can be solved when there is a tight balance between excitatory and inhibitory input. In this case, small synaptic modifications applied to the many synapses onto a given neuron disrupt that balance and produce a large effect even for modifications induced by a single stimulus. This effect makes fast learning possible with small synaptic changes and reconciles physiological and behavioral observations.
Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid Precursor Protein Knock-In Mouse Model of Alzheimer's Disease
Authors: Zhang Hua , Wu Lili , Pchitskaya Ekaterina , Zakharova Olga , Saito Takashi , Saido Takaomi , Bezprozvanny Ilya 
Published: September 2015

Alzheimer's disease (AD) is the most common reason for elderly dementia in the world. We proposed that memory loss in AD is related to destabilization of mushroom postsynaptic spines involved in long-term memory storage. We demonstrated previously that stromal interaction molecule 2 (STIM2)-regulated neuronal store-operated calcium entry (nSOC) in postsynaptic spines play a key role in stability of mushroom spines by maintaining activity of synaptic Ca2+/calmodulin kinase II (CaMKII). Furthermore, we demonstrated previously that the STIM2–nSOC–CaMKII pathway is downregulated in presenilin 1 M146V knock-in (PS1–M146V KI) mouse model of AD, leading to loss of hippocampal mushroom spines in this model. In the present study, we demonstrate that hippocampal mushroom postsynaptic spines are also lost in amyloid precursor protein knock-in (APPKI) mouse model of AD. We demonstrated that loss of mushroom spines occurs as a result of accumulation of extracellular β-amyloid 42 in APPKI culture media. Our results indicate that extracellular Aβ42acts by overactivating mGluR5 receptor in APPKI neurons, leading to elevated Ca2+levels in endoplasmic reticulum, compensatory downregulation of STIM2 expression, impaired synaptic nSOC, and reduced CaMKII activity. Pharmacological inhibition of mGluR5 or overexpression of STIM2 rescued synaptic nSOC and prevented mushroom spine loss in APPKI hippocampal neurons. Our results indicate that downregulation of synaptic STIM2–nSOC–CaMKII pathway causes loss of mushroom synaptic spines in both presenilin and APPKI mouse models of AD. We propose that modulators/activators of this pathway may have a potential therapeutic value for treatment of memory loss in AD.SIGNIFICANCE STATEMENTA direct connection between amyloid-induced synaptic mushroom spine loss and neuronal store-operated calcium entry pathway is shown. These results provide strong support for the calcium hypothesis of neurodegeneration and further validate the synaptic store-operated calcium entry pathway as a potential therapeutic target for Alzheimer's disease.
The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina
Authors: Murphy-Baum Benjamin L. , Taylor W. Rowland 
Published: September 2015

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells.SIGNIFICANCE STATEMENTThe retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene.
Intracortical and Thalamocortical Connections of the Hand and Face Representations in Somatosensory Area 3b of Macaque Monkeys and Effects of Chronic Spinal Cord Injuries
Authors: Chand Prem , Jain Neeraj 
Published: September 2015

Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at cervical levels undergo large-scale reorganization. Reorganization results in expansion of intact chin inputs, which reactivate neurons in the deafferented hand representation in the primary somatosensory cortex (area 3b), ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A likely contributing mechanism for this large-scale plasticity is sprouting of axons across the hand–face border. Here we determined whether such sprouting takes place in area 3b. We first determined the extent of intrinsic corticocortical connectivity between the hand and the face representations in normal area 3b. Small amounts of neuroanatomical tracers were injected in these representations close to the electrophysiologically determined hand–face border. Locations of the labeled neurons were mapped with respect to the detailed electrophysiological somatotopic maps and histologically determined hand–face border revealed in sections of the flattened cortex stained for myelin. Results show that intracortical projections across the hand–face border are few. In monkeys with chronic unilateral lesions of the dorsal columns and expanded chin representation, connections across the hand–face border were not different compared with normal monkeys. Thalamocortical connections from the hand and face representations in the ventroposterior nucleus to area 3b also remained unaltered after injury. The results show that sprouting of intrinsic connections in area 3b or the thalamocortical inputs does not contribute to large-scale cortical plasticity.SIGNIFICANCE STATEMENTLong-term injuries to dorsal spinal cord in adult primates result in large-scale somatotopic reorganization due to which chin inputs expand into the deafferented hand region. Reorganization takes place in multiple cortical areas, and thalamic and medullary nuclei. To what extent this brain reorganization due to dorsal column injuries is related to axonal sprouting is not known. Here we show that reorganization of primary somatosensory area 3b is not accompanied with either an increase in intrinsic cortical connections between the hand and face representations, or any change in thalamocortical inputs to these areas. Axonal sprouting that causes reorganization likely takes place at subthalamic levels.
Bidirectional Modulation of Recognition Memory
Authors: Ho Jonathan W. , Poeta Devon L. , Jacobson Tara K. , Zolnik Timothy A. , Neske Garrett T. , Connors Barry W. , Burwell Rebecca D. 
Published: September 2015

Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30–40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30–40 Hz was not effective in increasing exploration of novel images. Stimulation at 10–15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally.SIGNIFICANCE STATEMENTRecognition of novelty and familiarity are important for learning, memory, and decision making. Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects, but how novelty and familiarity are encoded and transmitted in the brain is not known. Perirhinal neurons respond to novelty and familiarity by changing firing rates, but recent work suggests that brain oscillations may also be important for recognition. In this study, we showed that stimulation of the PER could increase or decrease exploration of novel and familiar images depending on the frequency of stimulation. Our findings suggest that optical stimulation of PER at specific frequencies can predictably alter recognition memory.
Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling
Authors: González Oscar C. , Krishnan Giri P. , Chauvette Sylvain , Timofeev Igor , Sejnowski Terrence , Bazhenov Maxim 
Published: September 2015

Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Ourin vivoexperimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals.SIGNIFICANCE STATEMENTTraumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy.
Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance
Authors: Majaj Najib J. , Hong Ha , Solomon Ethan A. , DiCarlo James J. 
Published: September 2015

To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT (“face patches”) did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates.SIGNIFICANCE STATEMENTWe sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a database of images for evaluating object recognition performance. We used multielectrode arrays to characterize hundreds of neurons in the visual ventral stream of nonhuman primates and measured the object recognition performance of >100 human observers. Remarkably, we found that simple learned weighted sums of firing rates of neurons in monkey inferior temporal (IT) cortex accurately predicted human performance. Although previous work led us to expect that IT would outperform V4, we were surprised by the quantitative precision with which simple IT-based linking hypotheses accounted for human behavior.
Digital diagnostics apparently healthy periodontitis on three-dimensional reconstraction of cone beam computed tomography
Authors: Ронь Галина , Ron' G. , Еловикова Татьяна , Elovicova T. , Уварова Л. , Uvarova L. , Чибисова М. , Chibisova M. 
Published: September 2015

<div style="left: 1039.39px; top: 511.712px; font-size: 20px; font-family: serif; transform: scaleX(1.01448);" data-canvas-width="684.0280000000007">Radiological examination of almost healthy patient on the cone beam computer tomograph for the purpose of determination density levels of maxillofacial area bone concerning density of the teeth roots is conducted. Three-dimensional reconstruction of teeth roots and surrounding tissues was positioned as a dental volume tomography with possibility of densitometry. The level of bone density relative to the density of the central teeth roots of the lower jaw (the buttress of the lower jaw) is an objective criterion of the condition of periodontal tissues, which also allows to compare the obtained data with the numeric criteria for various forms of chronic generalized periodontitis.</div>
Injuries and illnesses among Federal Emergency Management Agency–certified search-and-recovery and search-and-rescue dogs deployed to Oso, Washington, following the March 22, 2014, State Route 530 landslide
Authors: Gordon Lori E. 
Published: September 2015

Abstract
Objective—To establish types and rates of injuries and illnesses among search-and-recovery and search-and-rescue dogs deployed to Oso, Wash, following the March 22, 2014, State Route 530 landslide.
Design—Medical records review and cross-sectional survey.
Animals—25 Federal Emergency Management Agency–certified search dogs.
Procedures—On-site medical records and postdeployment laboratory test results were reviewed and an electronic survey was distributed to handlers within 8 days after demobilization.
Results—Dogs worked a total of 244 search shifts totaling 2,015 hours. Injuries and illnesses were reported in 21 (84%) dogs. Wounds (abrasions, pad wear, paw pad splits, and lacerations) were the most common injury, with an incidence rate of 28.3 wounds/1,000 hours worked. Dehydration was the most common illness, with an incidence rate of 10.4 cases of dehydration/1,000 hours worked. Total incidence rate for all health events was 66.5 events/1,000 hours worked. Two search dogs were removed from search operations for 2 days because of health issues. All others continued search operations while receiving treatment for their medical issues. All health issues were resolved during the deployment or within 2 weeks after demobilization.
Conclusions and Clinical Relevance—Results revealed that search dogs deployed to the Oso, Wash, landslide incurred injuries and illnesses similar to those reported following other disasters (dehydration, wounding, vomiting, and diarrhea) but also incurred medical issues not previously documented (acute caudal myopathy, cutaneous mass ruptures, and fever). The reported medical issues were minor; however, prompt veterinary care helped prevent them from developing into more serious conditions.
Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections
Authors: Jacob Megan E. , Hoppin Jane A. , Steers Nicola , Davis Jennifer L. , Davidson Gigi , Hansen Bernie , Lunn Katharine F. , Murphy K. Marcia , Papich Mark G. 
Published: September 2015

Abstract
Objective—To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections.
Design—Cross-sectional survey.
Sample—71 veterinarians.
Procedures—An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance.
Results—Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns.
Conclusions and Clinical Relevance—Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals.
Survey evidence of members’ willingness to invest in agricultural hybrid cooperatives
Authors: Alho E. 
Published: September 2015

Abstract
Agricultural producer organisations face tight competition in global food and agricultural markets. The opportunities for cooperatives to acquire growth capital are restricted to member contributions, which poses a financial handicap in competition against investor-owned firms. Innovative cooperative structures have emerged as a response to the competitive pressures. For many, gaining access to growth capital from investors has been the reason for departing from the traditional cooperative organisational structure. This study examined whether farmers, as members and owners of agricultural producer cooperatives, are willing to invest in cooperative growth. By using the members of two large Finnish meat producer cooperatives as a sample we were able to utilise the variability in investor-owned firm structures, in which the members have both direct and indirect ownership in two layers of the agricultural producer organisation. A questionnaire study was conducted, including a contingent rating task in which farmers stated the point in the hybrid organisation chain at which they preferred to invest. The results indicated that the majority of farmers were willing to invest and the tendency increased with farm size. The average investment sum is considerable relative to the current capital contribution of an average member. The most preferred form was traditional cooperative capital, while a comparison of investment alternatives suggested that farmers are not yet receptive to new transferable cooperative shares. Retaining control appears important to producers. Farmer commitment erodes when the firm is in financial difficulties. Less member capital is available to save the firm from a cash crisis compared to a scenario of investments improving competitiveness.