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Results for “Neuroscience”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 739 records · Page 41Linked to original sources

bioRxiv2016

Two frequency bands contain the most stimulus-related information in visual cortex

Sensory cortices represent the world through the activity of diversely tuned cells. How the activity of single cells is coordinated within populations and across sensory hierarchies is largely unknown. Cortical oscillations may coordinate local and distributed neuronal groups. Using datasets from intracortical multi-electrode recordings and from large-scale electrocorticography (ECoG) grids, we investigated how visual features could be extracted from the local field potential (LFP) and how this compared with the information available from multi-unit activity (MUA). MUA recorded from macaque V1 contained comparable amounts of information as simultaneously recorded LFP power in two frequency bands, one in the alpha-beta band and the other in the gamma band. ECoG-LFP contained information in the same bands as microelectrode-LFP, even when identifying natural scenes. The fact that information was contained in the same bands in both intracortical and ECoG recordings suggests that oscillatory activity could play similar roles at both spatial scales.

Neuroscience↗

bioRxiv2016

HDAC inhibition protects degenerating cone photoreceptors in vivo

Retinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

Neuroscience↗

bioRxiv2016

Cytokine and Leukocyte Profiling Reveal Pro-Inflammatory and Autoimmune Features in Frontotemporal Dementia Patients

The growing link between systemic environment and brain function opens the possibility that cellular communication and composition in blood are correlated with brain health. We tested this concept in frontotemporal dementia with novel, unbiased tools that measure hundreds of soluble signaling proteins or characterize the vast immune cell repertoire in blood. With these tools we discovered complementary abnormalities indicative of abnormal T cell populations and autoimmunity in frontotemporal dementia.

Neuroscience↗

bioRxiv2016

The hippocampus generalizes across memories that share item and context information

Episodic memory is known to rely on the hippocampus, but how the hippocampus organizes different episodes to permit their subsequent retrieval remains controversial. According to one view, hippocampal coding differentiates between similar events to reduce interference, whereas an alternative view is that the hippocampus assigns similar representations to events that share item and context information. Here, we used multivariate analyses of activity patterns measured with functional magnetic resonance imaging (fMRI) to characterize how the hippocampus distinguishes between memories based on similarity of their item and/or context information. Hippocampal activity patterns discriminated between events that shared either item or context information, but generalized across events that shared similar item-context associations. The current findings provide novel evidence that, whereas the hippocampus can resist mnemonic interference by separating events that generalize along a single attribute dimension, overlapping hippocampal codes may support memory for events with overlapping item-context relations.

Neuroscience↗

bioRxiv2016

Olfactory perception of chemically diverse molecules

Background: Understanding the relationship between a stimulus and how it is perceived reveals fundamental principles about the mechanisms of sensory perception. While this stimulus-percept problem is mostly understood for color vision and tone perception, it is not currently possible to predict how a given molecule smells. While there has been some progress in predicting the pleasantness and intensity of an odor, perceptual data for a larger number of diverse molecules are needed to improve current predictions. Towards this goal, we tested the olfactory perception of 480 structurally and perceptually diverse molecules at two concentrations using a panel of 55 healthy human subjects.\n\nResults: For each stimulus, we collected data on perceived intensity, pleasantness, and familiarity. In addition, subjects were asked to apply 20 semantic odor quality descriptors to these stimuli, and were offered the option to describe the smell in their own words. Using this dataset, we replicated several previous correlations between molecular features of the stimulus and olfactory perception. The number of sulfur atoms in a molecule was highly correlated with the descriptors \"garlic\" \"fish\" \"decayed,\" and large and structurally complex molecules were perceived to be more pleasant. We discovered a number of strong correlations in intensity perception between molecules, which suggests a shared mechanism for perceiving these molecules. We show that familiarity had a strong effect on the ability of subjects to describe a smell. Many subjects used commercial products to describe familiar odors, highlighting the role of prior experience in biasing verbal report of perceived smells. Nonspecific descriptors like \"chemical\" were applied frequently to unfamiliar smells, and unfamiliar odors were generally rated as neither pleasant nor unpleasant.\n\nConclusions: We present a very large psychophysical dataset and use this to correlate molecular features of a stimulus to olfactory percept. Our work reveals robust correlations between molecular features and perceptual qualities, and highlights the dominant role of familiarity and experience in assigning verbal descriptors to smells.

Neuroscience↗

bioRxiv2016

Subcortical source and modulation of the narrowband gamma oscillation in mouse visual cortex

Primary visual cortex (V1) exhibits two types of gamma rhythm: broadband activity in the 30-90 Hz range, and a narrowband oscillation seen in mice at frequencies close to 60 Hz. We investigated the sources of the narrowband gamma oscillation, the factors modulating its strength, and its relationship to broadband gamma activity. Narrowband and broadband gamma power were uncorrelated. Increasing visual contrast had opposite effects on the two rhythms: it increased broadband activity, but suppressed the narrowband oscillation. The narrowband oscillation was strongest in layer 4, and was mediated primarily by excitatory currents entrained by the synchronous, rhythmic firing of neurons in the lateral geniculate nucleus (LGN). The power and peak frequency of the narrowband gamma oscillation increased with light intensity. Silencing the cortex optogenetically did not affect narrowband oscillation in either LGN firing or cortical excitatory currents, suggesting that this oscillation reflects unidirectional flow of signals from thalamus to cortex.\n\nHighlights*Local field potential in mouse primary visual cortex exhibits a pronounced narrowband gamma oscillation close to 60 Hz.\n\n*Narrowband gamma is highest in the thalamorecipient layer 4\n\n*Narrowband gamma increases with light intensity and arousal state, and is suppressed by visual contrast.\n\n*Lateral geniculate nucleus neurons fire synchronously at the narrowband gamma frequency, independent of V1 activity.

Neuroscience↗

bioRxiv2016

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

We have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF RGC types, but also unveiled differences between dorsal and ventral RGCs. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF RGCs exhibited antagonistic behavior, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, responses to light get stronger, and centers become more circular while seeing differences in all of them between RGC types. These findings show that retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour the early development of dorsal retina, and reflecting different roles in vision in the mature animal.

Neuroscience↗

bioRxiv2016

Alpha Phase Dynamics Predict Age-Related Visual Working Memory Decline

Alpha oscillations are modulated in response to visual temporal and spatial cues, However, the neural response to alerting cues is less explored, as is how this response is affected by healthy aging. Using scalp EEG, we examined how visual cortical alpha activity relates to working memory performance. Younger (20-30 years) and older (60-70 years) participants were presented with a visual alerting cue uninformative of the position or size of a lateralized working memory array. Older adults showed longer response times overall, and reduced accuracy when memory load was high. Older adults had less consistent cue-evoked phase resetting than younger adults, which predicted worse performance. Alpha phase prior to memory array presentation predicted response time, but the relationship between phase and response time was weaker in older adults. These results suggest that changes in alpha phase dynamics, especially prior to presentation of task-relevant stimuli, potentially contribute to age-related cognitive decline.

Neuroscience↗

bioRxiv2016

Paradoxical signaling regulates structural plasticity in dendritic spines

Transient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine en{-}largement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling net{-}works and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remod{-}eling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.

Neuroscience↗

bioRxiv2016

Induction of Kanizsa contours requires awareness of the inducing context

It remains unknown to what extent the human visual system interprets information about complex scenes without conscious analysis. Here we used visual masking techniques to assess whether illusory contours (Kanizsa shapes) are perceived when the inducing context creating this illusion does not reach awareness. In the first experiment we tested perception directly by having participants discriminate the orientation of an illusory contour. In the second experiment, we exploited the fact that the presence of an illusory contour enhances performance on a spatial localization task. Moreover, in the latter experiment we also used a different masking method to rule out the effect of stimulus duration. Our results suggest that participants do not perceive illusory contours when they are unaware of the inducing context. This is consistent with theories of a multistage, recurrent process of perceptual integration. Our findings thus challenge some reports, including those from neurophysiological experiments in anaesthetized animals. Furthermore, we discuss the importance to test the presence of the phenomenal percept directly with appropriate methods.

Neuroscience↗

bioRxiv2016

Carbon nanotube electrodes for retinal implants: a study of structural and functional integration over time

The choice of electrode material is of paramount importance in neural prosthetic devices. Electrodes must be biocompatible yet able to sustain repetitive current injections in a highly corrosive environment. We explored the suitability of carbon nanotube (CNT) electrodes to stimulate retinal ganglion cells (RGCs) in a mouse model of outer retinal degeneration. We investigated morphological changes at the bio-hybrid interface and changes in RGC responses to electrical stimulation following prolonged in vitro coupling to CNT electrodes. We observed gradual remodelling of the inner retina to incorporate CNT assemblies. Electrophysiological recordings demonstrate a progressive increase in coupling between RGCs and the CNT electrodes over three days, characterized by a gradual decrease in stimulation thresholds and increase in cellular recruitment. These results provide novel evidence for time-dependent formation of viable bio-hybrids between CNTs and the retina, demonstrating that CNTs are a promising material for inclusion in retinal prosthetic devices.

Neuroscience↗

bioRxiv2016

Subiculum neurons map the current axis of travel

Travel constrained to paths, a common navigational context, demands knowledge of spatial relationships between routes, their components, and their positioning in the larger environment. During traversal of an environment composed of multiple interconnected paths, a subpopulation of subiculum neurons robustly encoded the animals current axis of travel. The firing of these axis-tuned neurons peaked bimodally at head orientations approximately 180 degrees apart. Track rotation experiments revealed that axis encoding carried the spatial reference frame of the larger environment as opposed to the track itself. However, axis-tuned activity of the same subpopulation was largely absent during unconstrained movement about a circular arena. Thus, during navigation in a path-rich environment, subpopulations of subiculum neurons encode the animals current axis of travel relative to environmental boundaries - providing a powerful mechanism for mapping of specific relationships between routes, route components, and the larger environment.

Neuroscience↗

bioRxiv2016

Imaging decision-related neural cascades in the human brain

Perceptual decisions depend on coordinated patterns of neural activity cascading across the brain, running in time from stimulus to response and in space from primary sensory regions to the frontal lobe. Measuring this cascade and how it flows through the brain is key to developing an understanding of how our brains function. However observing, let alone understanding, this cascade, particularly in humans, is challenging. Here, we report a significant methodological advance allowing this observation in humans at unprecedented spatiotemporal resolution. We use a novel encoding model to link simultaneously measured electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) signals to infer the high-resolution spatiotemporal brain dynamics taking place during rapid visual perceptual decision-making. After demonstrating the methodology replicates past results, we show that it uncovers a previously unobserved sequential reactivation of a substantial fraction of the pre-response network whose magnitude correlates with decision confidence. Our results illustrate that a temporally coordinated and spatially distributed neural cascade underlies perceptual decision-making, with our methodology illuminating complex brain dynamics that would otherwise be unobservable using conventional fMRI or EEG separately. We expect this methodology to be useful in observing brain dynamics in a wide range of other mental processes.

Neuroscience↗

bioRxiv2016

Artefactual origin of biphasic cortical spike-LFP correlation

Electrophysiological data acquisition systems introduce various distortions into the signals they record. While such distortions were discussed previously, their effects are often not appreciated. Here I show that the biphasic shape of cortical spike-triggered LFP average (stLFP), reported in multiple studies, is likely an artefact introduced by high-pass filter of the neural data acquisition system when the actual stLFP has a single trough around the zero lag.

Neuroscience↗

bioRxiv2016

Reduced spatial integration in the ventral visual cortex underlies face recognition deficits in developmental prosopagnosia

Developmental prosopagnosia (DP) is characterized by deficits in face recognition without gross brain abnormalities. However, the neural basis of DP is not well understood. We measured population receptive fields (pRFs) in ventral visual cortex of DPs and typical adults to assess the contribution of spatial integration to face processing. While DPs showed typical retinotopic organization of ventral visual cortex and normal pRF sizes in early visual areas, we found significantly reduced pRF sizes in face-selective regions and in intermediate areas hV4 and VO1. Across both typicals and DPs, face recognition ability correlated positively with pRF size in both face-selective regions and VO1, whereby participants with larger pRFs perform better. However, face recognition ability is correlated with both pRF size and ROI volume only in face-selective regions. These findings suggest that smaller pRF sizes in DP may reflect a deficit in spatial integration affecting holistic processing required for face recognition.

Neuroscience↗

bioRxiv2016

CRISPR-Cas9 targeted deletion of the C9orf72 repeat expansion mutation corrects cellular phenotypes in patient-derived iPS cells

The large hexanucleotide (GGGGCC) repeat expansion in the non-coding promoter region of C9orf72 is the leading cause of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Mechanisms underlying neurodegeneration are not clear, and both a C9orf72 loss of function and a gain of toxicity, in the form of RNA foci or dipeptide repeat deposition, are implicated. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-mediated genome editing is an attractive strategy for disease modeling and therapeutic intervention. Here we show that this system can be utilized to completely remove the large repeat expansion mutation within C9orf72 in patient-derived induced pluripotent stem (iPS) cells. Removal of the mutation prevented RNA foci formation and promoter hypermethylation, two phenotypes of the C9orf72 mutation. Interestingly, these changes did not significantly alter C9orf72 expression at the mRNA or protein level. This work provides a proof-of-principle for the use of CRISPR-Cas9-mediated excision of the pathogenic C9orf72 repeat expansion as a therapeutic strategy in FTD/ALS.\n\nOne Sentence SummaryCRISPR-Cas9-mediated excision of the large C9orf72 repeat expansion mutation rescues RNA foci formation and promoter hypermethylation without altering C9orf72 transcript and protein expression.

Neuroscience↗

bioRxiv2016

Dendritic spine taxonomy and shape transition analysis

The common approach in morphological analysis of dendritic spines is to categorize spines into subpopulations based on whether they are stubby, mushroom, thin, or filopodia. Corresponding cellular models of synaptic plasticity, long-term potentiation, and long-term depression associate synaptic strength with either spine enlargement or spine shrinkage. Although a variety of automatic spine segmentation and feature extraction methods were developed recently, no approaches allowing for an automatic and unbiased distinction between dendritic spine subpopulations and detailed computational models of spine behavior exist.\n\nWe propose an automatic and statistically based method for the unsupervised construction of spine shape taxonomy based on arbitrary features. The taxonomy is then utilized in the newly introduced computational model of behavior, which relies on transitions between shapes. Models of different populations are compared using supplied bootstrap-based statistical tests.\n\nWe compared two populations of spines at two time points. The first population was stimulated with long-term potentiation, and the other in the resting state was used as a control. The comparison of shape transition characteristics allowed us to identify differences between population behaviors. Although some extreme changes were observed in the stimulated population, statistically significant differences were found only when whole models were compared. Therefore, we hypothesize that the learning process is related to the subtle changes in the whole ensemble of different dendritic spine structures, but not at the level of single shape classes.\n\nThe source code of our software is freely available for non-commercial use1.

Neuroscience↗

bioRxiv2016

Systematic exploration of unsupervised methods for mapping behavior

To fully understand the mechanisms giving rise to behavior, we need to be able to precisely measure it. When coupled with large behavioral data sets, unsupervised clustering methods offer the potential of unbiased mapping of behavioral spaces. However, unsupervised techniques to map behavioral spaces are in their infancy, and there have been few systematic considerations of all the methodological options. We compared the performance of seven distinct mapping methods in clustering a data set consisting of the x-and y-positions of the six legs of individual flies. Legs were automatically tracked by small pieces of fluorescent dye, while the fly was tethered and walking on an air-suspended ball. We find that there is considerable variation in the performance of these mapping methods, and that better performance is attained when clustering is done in higher dimensional spaces (which are otherwise less preferable because they are hard to visualize). High dimensionality means that some algorithms, including the non-parametric watershed cluster assignment algorithm, cannot be used. We developed an alternative watershed algorithm which can be used in high-dimensional spaces when the probability density estimate can be computed directly. With these tools in hand, we examined the behavioral space of fly leg postural dynamics and locomotion. We find a striking division of behavior into modes involving the fore legs and modes involving the hind legs, with few direct transitions between them. By computing behavioral clusters using the data from all flies simultaneously, we show that this division appears to be common to all flies. We also identify individual-to-individual differences in behavior and behavioral transitions. Lastly, we suggest a computational pipeline that can achieve satisfactory levels of performance without the taxing computational demands of a systematic combinatorial approach.\n\nAbbreviationsGMM: Gaussian mixture model; PCA: principal components analysis; SW: sparse watershed; t-SNE: t-distributed stochastic neighbor embedding

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