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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 84,588 bioRxiv papers from 364,027 authors.

Most downloaded bioRxiv papers, all time

in category neuroscience

14,750 results found. For more information, click each entry to expand.

81: Distinct descending motor cortex pathways and their roles in movement
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Posted to bioRxiv 05 Dec 2017

Distinct descending motor cortex pathways and their roles in movement
4,794 downloads neuroscience

Michael N Economo, Sarada Viswanathan, Bosiljka Tasic, Erhan Bas, Johan Winnubst, Vilas Menon, Lucas Graybuck, Thuc Nghi Nguyen, Lihua Wang, Charles R. Gerfen, Jayaram Chandrashekar, Hongkui Zeng, Loren L. Looger, Karel Svoboda

Activity in motor cortex predicts specific movements, seconds before they are initiated. This preparatory activity has been observed in L5 descending "pyramidal tract" (PT) neurons. A key question is how preparatory activity can be maintained without causing movement, and how preparatory activity is eventually converted to a motor command to trigger appropriate movements. We used single cell transcriptional profiling and axonal reconstructions to identify two types of PT neuron. Both types share projections to multiple targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex. In a delayed-response task, these neurons produced early preparatory activity that persisted until the movement. The second type projects to motor centers in the medulla and produced late preparatory activity and motor commands. These results indicate that two motor cortex output neurons are specialized for distinct roles in motor control.

82: A guide to robust statistical methods in neuroscience
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Posted to bioRxiv 20 Jun 2017

A guide to robust statistical methods in neuroscience
4,785 downloads neuroscience

Rand R. Wilcox, Guillaume A. Rousselet

There is a vast array of new and improved methods for comparing groups and studying associations that offer the potential for substantially increasing power, providing improved control over the probability of a Type I error, and yielding a deeper and more nuanced under- standing of neuroscience data. These new techniques effectively deal with four insights into when and why conventional methods can be unsatisfactory. But for the non-statistician, the vast array of new and improved techniques for comparing groups and studying associations can seem daunting, simply because there are so many new methods that are now available. The paper briefly reviews when and why conventional methods can have relatively low power and yield misleading results. The main goal is to suggest some general guidelines regarding when, how and why certain modern techniques might be used.

83: Microstate EEGlab toolbox: An introductory guide
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Posted to bioRxiv 27 Mar 2018

Microstate EEGlab toolbox: An introductory guide
4,710 downloads neuroscience

Andreas Trier Poulsen, Andreas Pedroni, Nicolas Langer, Lars Kai Hansen

EEG microstate analysis offers a sparse characterisation of the spatio-temporal features of large-scale brain network activity. However, despite the concept of microstates is straight-forward and offers various quantifications of the EEG signal with a relatively clear neurophysiological interpretation, a few important aspects about the currently applied methods are not readily comprehensible. Here we aim to increase the transparency about the methods to facilitate widespread application and reproducibility of EEG microstate analysis by introducing a new EEGlab toolbox for Matlab. EEGlab and the Microstate toolbox are open source, allowing the user to keep track of all details in every analysis step. The toolbox is specifically designed to facilitate the development of new methods. While the toolbox can be controlled with a graphical user interface (GUI), making it easier for newcomers to take their first steps in exploring the possibilities of microstate analysis, the Matlab framework allows advanced users to create scripts to automatise analysis for multiple subjects to avoid tediously repeating steps for every subject. This manuscript provides an overview of the most commonly applied microstate methods as well as a tutorial consisting of a comprehensive walk-through of the analysis of a small, publicly available dataset.

84: Probing variability in a cognitive map using manifold inference from neural dynamics
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Posted to bioRxiv 16 Sep 2018

Probing variability in a cognitive map using manifold inference from neural dynamics
4,693 downloads neuroscience

Ryan J. Low, Sam Lewallen, Dmitriy Aronov, Rhino Nevers, David W. Tank

Hippocampal neurons fire selectively in local behavioral contexts such as the position in an environment or phase of a task, and are thought to form a cognitive map of task-relevant variables. However, their activity varies over repeated behavioral conditions, such as different runs through the same position or repeated trials. Although widely observed across the brain, such variability is not well understood, and could reflect noise or structure, such as the encoding of additional cognitive information. Here, we introduce a conceptual model to explain variability in terms of underlying, population-level structure in single-trial neural activity. To test this model, we developed a novel unsupervised learning algorithm incorporating temporal dynamics, in order to characterize population activity as a trajectory on a nonlinear manifold--a space of possible network states. The manifold's structure captures correlations between neurons and temporal relationships between states, constraints arising from underlying network architecture and inputs. Using measurements of activity over time but no information about exogenous behavioral variables, we recovered hippocampal activity manifolds during spatial and non-spatial cognitive tasks in rats. Manifolds were low dimensional and smoothly encoded task-related variables, but contained an extra dimension reflecting information beyond the measured behavioral variables. Consistent with our model, neurons fired as a function of overall network state, and fluctuations in their activity across trials corresponded to variation in the underlying trajectory on the manifold. In particular, the extra dimension allowed the system to take different trajectories despite repeated behavioral conditions. Furthermore, the trajectory could temporarily decouple from current behavioral conditions and traverse neighboring manifold points corresponding to past, future, or nearby behavioral states. Our results suggest that trial-to-trial variability in the hippocampus is structured, and may reflect the operation of internal cognitive processes. The manifold structure of population activity is well-suited for organizing information to support memory, planning, and reinforcement learning. In general, our approach could find broader use in probing the organization and computational role of circuit dynamics in other brain regions.

85: Spatial organization of the somatosensory cortex revealed by cyclic smFISH
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Posted to bioRxiv 04 Mar 2018

Spatial organization of the somatosensory cortex revealed by cyclic smFISH
4,689 downloads neuroscience

Simone Codeluppi, Lars Borm, Amit Zeisel, Gioele La Manno, Josina A van Lunteren, Camilla I. Svensson, Sten Linnarsson

The global efforts towards the creation of a molecular census of the brain using single-cell transcriptomics is generating a large catalog of molecularly defined cell types lacking spatial information. Thus, new methods are needed to map a large number of cell-specific markers simultaneously on large tissue areas. Here, we developed a cyclic single molecule fluorescence in situ hybridization methodology and defined the cellular organization of the somatosensory cortex using markers identified by single-cell transcriptomics.

86: Machine translation of cortical activity to text with an encoder-decoder framework
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Posted to bioRxiv 22 Jul 2019

Machine translation of cortical activity to text with an encoder-decoder framework
4,679 downloads neuroscience

Joseph G. Makin, David A. Moses, Edward F. Chang

A decade after the first successful attempt to decode speech directly from human brain signals, accuracy and speed remain far below that of natural speech or typing. Here we show how to achieve high accuracy from the electrocorticogram at natural-speech rates, even with few data (on the order of half an hour of spoken speech). Taking a cue from recent advances in machine translation and automatic speech recognition, we train a recurrent neural network to map neural signals directly to word sequences (sentences). In particular, the network first encodes a sentence-length sequence of neural activity into an abstract representation, and then decodes this representation, word by word, into an English sentence. For each participant, training data consist of several spoken repeats of a set of some 30-50 sentences, along with the corresponding neural signals at each of about 250 electrodes distributed over peri-Sylvian speech cortices. Average word error rates across a validation (held-out) sentence set are as low as 7% for some participants, as compared to the previous state of the art of greater than 60%. Finally, we show how to use transfer learning to overcome limitations on data availability: Training certain components of the network under multiple participants' data, while keeping other components (e.g., the first hidden layer) "proprietary," can improve decoding performance--despite very different electrode coverage across participants.

87: Aged blood inhibits hippocampal neurogenesis and activates microglia through VCAM1 at the blood-brain barrier
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Posted to bioRxiv 03 Jan 2018

Aged blood inhibits hippocampal neurogenesis and activates microglia through VCAM1 at the blood-brain barrier
4,664 downloads neuroscience

Hanadie Yousef, Cathrin J Czupalla, Davis Lee, Ashley Burke, Michelle Chen, Judith Zandstra, Elisabeth Berber, Benoit Lehallier, Vidhu Mathur, Ramesh V Nair, Liana Bonanno, Taylor Merkel, Markus Schwaninger, Stephen Quake, Eugene C Butcher, Tony Wyss-Coray

An aged circulatory environment can promote brain dysfunction and we hypothesized that the blood-brain barrier (BBB) mediates at least some of these effects. We observe brain endothelial cells (BECs) in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of Vascular Cell Adhesion Molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions. Concomitantly, the shed, soluble form of VCAM1 is prominently increased in the aged circulation of humans and mice, and aged plasma is sufficient to increase VCAM1 expression in cultured BECs and young mouse hippocampi. Systemic anti-VCAM1 antibody or genetic ablation of VCAM1 in BECs counteracts the detrimental effects of aged plasma on young brains and reverses aging aspects in old mouse brains. Thus, VCAM1 is a negative regulator of adult neurogenesis and inducer of microglial reactivity, establishing VCAM1 and the luminal side of the BBB as possible targets to treat age-related neurodegeneration.

88: Tractography-based connectomes are dominated by false-positive connections
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Posted to bioRxiv 07 Nov 2016

Tractography-based connectomes are dominated by false-positive connections
4,649 downloads neuroscience

Klaus H. Maier-Hein, Peter Neher, Jean-Christophe Houde, Marc-Alexandre Côté, Eleftherios Garyfallidis, Jidan Zhong, Maxime Chamberland, Fang-Cheng Yeh, Ying-Chia Lin, Qing Ji, Wilburn E. Reddick, John O. Glass, David Qixiang Chen, Yuanjing Feng, Chengfeng Gao, Ye Wu, Jieyan Ma, H Renjie, Qiang Li, Carl-Fredrik Westin, Samuel Deslauriers-Gauthier, J. Omar Ocegueda González, Michael Paquette, Samuel St-Jean, Gabriel Girard, François Rheault, Jasmeen Sidhu, Chantal M.W. Tax, Fenghua Guo, Hamed Y. Mesri, Szabolcs Dávid, Martijn Froeling, Anneriet M. Heemskerk, Alexander Leemans, Arnaud Boré, Basile Pinsard, Christophe Bedetti, Matthieu Desrosiers, Simona Brambati, Julien Doyon, Alessia Sarica, Roberta Vasta, Antonio Cerasa, Aldo Quattrone, Jason Yeatman, Ali R. Khan, Wes Hodges, Simon Alexander, David Romascano, Muhamed Barakovic, Anna Auría, Oscar Esteban, Alia Lemkaddem, Jean-Philippe Thiran, H. Ertan Cetingul, Benjamin L. Odry, Boris Mailhe, Mariappan S. Nadar, Fabrizio Pizzagalli, Gautam Prasad, Julio E. Villalon-Reina, Justin Galvis, Paul M. Thompson, Francisco De Santiago Requejo, Pedro Luque Laguna, Luis Miguel Lacerda, Rachel Barrett, Flavio Dell’Acqua, Marco Catani, L Petit, Emmanuel Caruyer, Alessandro Daducci, Tim B Dyrby, Tim Holland-Letz, Claus C. Hilgetag, Bram Stieltjes, Maxime Descoteaux

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

89: A genetically encoded fluorescent sensor for in vivo imaging of GABA
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Posted to bioRxiv 14 May 2018

A genetically encoded fluorescent sensor for in vivo imaging of GABA
4,618 downloads neuroscience

Jonathan S. Marvin, Yoshiteru Shimoda, Vincent Malgoire, Marco Leite, Takashi Kawashima, Thomas P. Jensen, Erika L Knott, Ondrej Novak, Kaspar Podgorski, Nancy J Leidenheimer, Dmitri A. Rusakov, Misha B. Ahrens, Dimitri M Kullmann, Loren L. Looger

Current techniques for monitoring GABA, the primary inhibitory neurotransmitter in vertebrates, cannot follow ephemeral transients in intact neural circuits. We applied the design principles used to create iGluSnFR, a fluorescent reporter of synaptic glutamate, to develop a GABA sensor using a protein derived from a previously unsequenced Pseudomonas fluorescens strain. Structure-guided mutagenesis and library screening led to a usable iGABASnFR (maximum DeltaF/F ~ 2.5, Kd ~ 9 micromolar, good specificity, adequate kinetics). iGABASnFR is genetically encoded, detects single action potential-evoked GABA release events in culture, and produces readily detectable fluorescence increases in vivo in mice and zebrafish. iGABASnFR enabled tracking of: (1) mitochondrial GABA content and its modulation by an anticonvulsant; (2) swimming-evoked GABAergic transmission in zebrafish cerebellum; (3) GABA release events during inter-ictal spikes and seizures in awake mice; and (4) GABAergic tone decreases during isoflurane anesthesia. iGABASnFR will permit high spatiotemporal resolution of GABA signaling in intact preparations.

90: Distributed correlates of visually-guided behavior across the mouse brain
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Posted to bioRxiv 20 Nov 2018

Distributed correlates of visually-guided behavior across the mouse brain
4,608 downloads neuroscience

Nicholas A. Steinmetz, Peter Zatka-Haas, Matteo Carandini, Kenneth D. Harris

Behavior arises from neuronal activity, but it is not known how the active neurons are distributed across brain regions and how their activity unfolds in time. Here, we used high-density Neuropixels probes to record from ~30,000 neurons in mice performing a visual contrast discrimination task. The task activated 60% of the neurons, involving nearly all 42 recorded brain regions, well beyond the regions activated by passive visual stimulation. However, neurons selective for choice (left vs. right) were rare, and found mostly in midbrain, striatum, and frontal cortex. Those in midbrain were typically activated prior to contralateral choices and suppressed prior to ipsilateral choices, consistent with a competitive midbrain circuit for adjudicating the subject's choice. A brain-wide state shift distinguished trials in which visual stimuli led to movement. These results reveal concurrent representations of movement and choice in neurons widely distributed across the brain.

91: The Dreem Headband as an Alternative to Polysomnography for EEG Signal Acquisition and Sleep Staging
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Posted to bioRxiv 10 Jun 2019

The Dreem Headband as an Alternative to Polysomnography for EEG Signal Acquisition and Sleep Staging
4,595 downloads neuroscience

Pierrick J Arnal, Valentin Thorey, Michael E. Ballard, Albert Bou Hernandez, Antoine Guillot, Hugo Jourde, Mason Harris, Mathias Guillard, Pascal Van Beers, Mounir Chennaoui, Fabien Sauvet

Despite the central role of sleep in our lives and the high prevalence of sleep disorders, sleep is still poorly understood. The development of ambulatory technologies capable of monitoring brain activity during sleep longitudinally is critical to advancing sleep science and facilitating the diagnosis of sleep disorders. We introduced the Dreem headband (DH) as an affordable, comfortable, and user-friendly alternative to polysomnography (PSG). The purpose of this study was to assess the signal acquisition of the DH and the performance of its embedded automatic sleep staging algorithms compared to the gold-standard clinical PSG scored by 5 sleep experts. Thirty-one subjects completed an over-night sleep study at a sleep center while wearing both a PSG and the DH simultaneously. We assessed 1) the EEG signal quality between the DH and the PSG, 2) the heart rate, breathing frequency, and respiration rate variability (RRV) agreement between the DH and the PSG, and 3) the performance of the DH's automatic sleep staging according to AASM guidelines vs. PSG sleep experts manual scoring. Results demonstrate a strong correlation between the EEG signals acquired by the DH and those from the PSG, and the signals acquired by the DH enable monitoring of alpha (r= 0.71 ± 0.13), beta (r= 0.71 ± 0.18), delta (r = 0.76 ± 0.14), and theta (r = 0.61 ± 0.12) frequencies during sleep. The mean absolute error for heart rate, breathing frequency and RRV was 1.2 ± 0.5 bpm, 0.3 ± 0.2 cpm and 3.2 ± 0.6%, respectively. Automatic Sleep Staging reached an overall accuracy of 83.5 ± 6.4% (F1 score : 83.8 ± 6.3) for the DH to be compared with an average of 86.4 ± 8.0% (F1 score: 86.3 ± 7.4) for the five sleep experts. These results demonstrate the capacity of the DH to both precisely monitor sleep-related physiological signals and process them accurately into sleep stages. This device paves the way for high-quality, large-scale, longitudinal sleep studies.

92: I TRIED A BUNCH OF THINGS: THE DANGERS OF UNEXPECTED OVERFITTING IN CLASSIFICATION
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Posted to bioRxiv 03 Oct 2016

I TRIED A BUNCH OF THINGS: THE DANGERS OF UNEXPECTED OVERFITTING IN CLASSIFICATION
4,491 downloads neuroscience

Michael Powell, Mahan Hosseini, John Collins, Chloe Callahan-Flintoft, William Jones, Howard Bowman, Brad Wyble

Machine learning is a powerful set of techniques that has enhanced the abilities of neuroscientists to interpret information collected through EEG, fMRI, and MEG data. With these powerful techniques comes the danger of overfitting of hyper-parameters which can render results invalid, and cause a failure to generalize beyond the data set. We refer to this problem as ‘over-hyping’ and show that it is pernicious despite commonly used precautions. In particular, over-hyping occurs when an analysis is run repeatedly with slightly different analysis parameters and one set of results is selected based on the analysis. When this is done, the resulting method is unlikely to generalize to a new dataset, rendering it a partially, or perhaps even completely spurious result that will not be valid outside of the data used in the original analysis. While it is commonly assumed that cross-validation is an effective protection against such spurious results generated through overfitting or overhyping, this is not actually true. In this article, we show that both one-shot and iterative optimization of an analysis are prone to over-hyping, despite the use of cross-validation. We demonstrate that non-generalizable results can be obtained even on non-informative (i.e. random) data by modifying hyper-parameters in seemingly innocuous ways. We recommend a number of techniques for limiting over-hyping, such as lock-boxes, blind analyses, pre-registrations, and nested cross-validation. These techniques, are common in other fields that use machine learning, including computer science and physics. Adopting similar safeguards is critical for ensuring the robustness of machine-learning techniques in the neurosciences.

93: Filter-banks and artificial intelligence in seizure detection using electroencephalograms
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Posted to bioRxiv 03 Feb 2017

Filter-banks and artificial intelligence in seizure detection using electroencephalograms
4,478 downloads neuroscience

M. A. Pinto-Orellana, F. R. Cerqueira

Epilepsy is the most typical neurological disease in the world, and it implies an expensive and specialized diagnosis process based on electroencephalograms and video recordings. We developed a method that only requires the brainwave provided by the difference between two standard-located electrodes. Our proposed technique separates the original signal using a filter array with three different types of filters, and then extracts several features based on information theory and statistical information. In our study, we found that only 10 characteristics, of which the most important are related to higher frequencies, are required to offer an accuracy of 94%, a specificity of 95% and a sensitivity of 87% using C4.5 decision trees.

94: High precision coding in visual cortex
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Posted to bioRxiv 21 Jun 2019

High precision coding in visual cortex
4,470 downloads neuroscience

Carsen Stringer, Michalis Michaelos, Marius Pachitariu

Single neurons in visual cortex provide unreliable measurements of visual features due to their high trial-to-trial variability. It is not known if this “noise” extends its effects over large neural populations to impair the global encoding of stimuli. We recorded simultaneously from ∼20,000 neurons in mouse primary visual cortex (V1) and found that the neural populations had discrimination thresholds of ∼0.34° in an orientation decoding task. These thresholds were nearly 100 times smaller than those reported behaviorally in mice. The discrepancy between neural and behavioral discrimination could not be explained by the types of stimuli we used, by behavioral states or by the sequential nature of perceptual learning tasks. Furthermore, higher-order visual areas lateral to V1 could be decoded equally well. These results imply that the limits of sensory perception in mice are not set by neural noise in sensory cortex, but by the limitations of downstream decoders.

95: Fixed versus mixed RSA: Explaining visual representations by fixed and mixed feature sets from shallow and deep computational models
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Posted to bioRxiv 03 Oct 2014

Fixed versus mixed RSA: Explaining visual representations by fixed and mixed feature sets from shallow and deep computational models
4,424 downloads neuroscience

Seyed-Mahdi Khaligh-Razavi, Linda Henriksson, Kendrick Kay, Nikolaus Kriegeskorte

Studies of the primate visual system have begun to test a wide range of complex computational object-vision models. Realistic models have many parameters, which in practice cannot be fitted using the limited amounts of brain-activity data typically available. Task performance optimization (e.g. using backpropagation to train neural networks) provides major constraints for fitting parameters and discovering nonlinear representational features appropriate for the task (e.g. object classification). Model representations can be compared to brain representations in terms of the representational dissimilarities they predict for an image set. This method, called representational similarity analysis (RSA), enables us to test the representational feature space as is (fixed RSA) or to fit a linear transformation that mixes the nonlinear model features so as to best explain a cortical area's representational space (mixed RSA). Like voxel/population-receptive-field modelling, mixed RSA uses a training set (different stimuli) to fit one weight per model feature and response channel (voxels here), so as to best predict the response profile across images for each response channel. We analysed response patterns elicited by natural images, which were measured with functional magnetic resonance imaging (fMRI). We found that early visual areas were best accounted for by shallow models, such as a Gabor wavelet pyramid (GWP). The GWP model performed similarly with and without mixing, suggesting that the original features already approximated the representational space, obviating the need for mixing. However, a higher ventral-stream visual representation (lateral occipital region) was best explained by the higher layers of a deep convolutional network, and mixing of its feature set was essential for this model to explain the representation. We suspect that mixing was essential because the convolutional network had been trained to discriminate a set of 1000 categories, whose frequencies in the training set did not match their frequencies in natural experience or their behavioural importance. The latter factors might determine the representational prominence of semantic dimensions in higher-level ventral-stream areas. Our results demonstrate the benefits of testing both the specific representational hypothesis expressed by a model's original feature space and the hypothesis space generated by linear transformations of that feature space.

96: Population imaging of neural activity in awake behaving mice in multiple brain regions
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Posted to bioRxiv 23 Apr 2019

Population imaging of neural activity in awake behaving mice in multiple brain regions
4,404 downloads neuroscience

Kiryl D Piatkevich, Seth Bensussen, Hua-an Tseng, Sanaya N. Shroff, Violeta Gisselle Lopez-Huerta, Demian Park, Erica E. Jung, Or A. Shemesh, Christoph Straub, Howard J. Gritton, Michael F. Romano, Emma Costa, Bernardo L. Sabatini, Zhanyan Fu, Edward S. Boyden, Xue Han

A longstanding goal in neuroscience has been to image membrane voltage, with high temporal precision and sensitivity, in awake behaving mammals. Here, we report a genetically encoded voltage indicator, SomArchon, which exhibits millisecond response times and compatibility with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable, by manyfold over previous reagents. SomArchon only requires conventional one-photon microscopy to achieve these high performance characteristics. These improvements enable population analysis of neural activity, both at the subthreshold and spiking levels, in multiple brain regions: cortex, hippocampus, and striatum of awake behaving mice. Using SomArchon, we detect both positive and negative responses of striatal neurons during movement, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examine how the intracellular subthreshold theta oscillations of hippocampal neurons govern spike output, finding that nearby cells can exhibit highly correlated subthreshold activities, even as they generate highly divergent spiking patterns.

97: Real-time spike sorting platform for high-density extracellular probes with ground-truth validation and drift correction
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Posted to bioRxiv 19 Jan 2017

Real-time spike sorting platform for high-density extracellular probes with ground-truth validation and drift correction
4,397 downloads neuroscience

James J. Jun, Catalin C. Mitelut, Chongxi Lai, Sergey L Gratiy, Costas A. Anastassiou, Timothy D Harris

Electrical recordings from a large array of electrodes give us access to neural population activity with single-cell, single-spike resolution. These recordings contain extracellular spikes which must be correctly detected and assigned to individual neurons. Despite numerous spike-sorting techniques developed in the past, a lack of high-quality ground-truth datasets hinders the validation of spike-sorting approaches. Furthermore, existing approaches requiring manual corrections are not scalable for hours of recordings exceeding 100 channels. To address these issues, we built a comprehensive spike-sorting pipeline that performs reliably under noise and probe drift by incorporating covariance-based features and unsupervised clustering based on fast density-peak finding. We validated performance of our workflow using multiple ground-truth datasets that recently became available. Our software scales linearly and processes up to 1000-channel recording in real-time using a single workstation. Accurate, real-time spike sorting from large recording arrays will enable more precise control of closed-loop feedback experiments and brain-computer interfaces.

98: CaImAn: An open source tool for scalable Calcium Imaging data Analysis
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Posted to bioRxiv 05 Jun 2018

CaImAn: An open source tool for scalable Calcium Imaging data Analysis
4,364 downloads neuroscience

Andrea Giovannucci, Johannes Friedrich, Pat Gunn, Jérémie Kalfon, Sue Ann Koay, Jiannis Taxidis, Farzaneh Najafi, Jeffrey L. Gauthier, Pengcheng Zhou, David W. Tank, Dmitri Chklovskii, Eftychios A. Pnevmatikakis

Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. Here we present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good performance on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn, we collected a corpus of ground truth annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons.

99: All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability
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Posted to bioRxiv 13 Mar 2018

All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability
4,327 downloads neuroscience

Yoav Adam, Jeong J Kim, Shan Lou, Yongxin Zhao, Daan Brinks, Hao Wu, Mohammed A. Mostajo-Radji, Simon Kheifets, Vicente Parot, Selmaan Chettih, Katherine J Williams, Samouil L Farhi, Linda Madisen, Christopher D. Harvey, Hongkui Zeng, Paola Arlotta, Robert E. Campbell, Adam E. Cohen

A technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states. Genetically encoded voltage indicators are a promising tool for these purposes, but were so far limited to single-cell recordings with marginal signal to noise ratio (SNR) in vivo. We developed improved near infrared voltage indicators, high speed microscopes and targeted gene expression schemes which enabled recordings of supra- and subthreshold voltage dynamics from multiple neurons simultaneously in mouse hippocampus, in vivo. The reporters revealed sub-cellular details of back-propagating action potentials, correlations in sub-threshold voltage between multiple cells, and changes in dynamics associated with transitions from resting to locomotion. In combination with optogenetic stimulation, the reporters revealed brain state-dependent changes in neuronal excitability, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behavior.

100: Single-cell in situ transcriptomic map of astrocyte cortical layer diversity
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Posted to bioRxiv 03 Oct 2018

Single-cell in situ transcriptomic map of astrocyte cortical layer diversity
4,324 downloads neuroscience

Omer Ali Bayraktar, Theresa Bartels, Damon Polioudakis, Staffan Holmqvist, Lucile Ben Haim, Adam M.H. Young, Kirti Prakash, Alexander Brown, Mercedes F. Paredes, Riki Kawaguchi, John Stockley, Khalida Sabeur, Sandra M. Chang, Eric Huang, Peter Hutchinson, Erik M. Ullian, Daniel H. Geschwind, Giovanni Coppola, David H. Rowitch

During organogenesis, patterns and gradients of gene expression underlie organization and diversified cell specification to generate complex tissue architecture. While the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells are diversified to mimic neuronal laminae or show distinct layering. To determine the molecular architecture of the mammalian cortex, we developed a high- content pipeline that can quantify single-cell gene expression in situ. The Large-area Spatial Transcriptomic (LaST) map confirmed expected cortical neuron layer organization and also revealed a novel neuronal identity signature. Screening 46 candidate genes for astrocyte diversity across the cortex, we identified grey matter superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from neurons. Astrocyte layers formed in early postnatal cortex and mostly persisted in adult mouse and human cortex. Mutations that shifted neuronal post-mitotic identity or organization were sufficient to alter glial layering, indicating an instructive role for neuronal cues. In normal mouse cortex, astrocyte layer patterns showed area diversity between functionally distinct cortical regions. These findings indicate that excitatory neurons and astrocytes cells are organized into distinct lineage-associated laminae, which give rise to higher order neuroglial complexity of cortical architecture.

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