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in category neuroscience

18,148 results found. For more information, click each entry to expand.

21: SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia
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Posted 18 Jul 2020

SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia
12,109 downloads bioRxiv neuroscience

Aubin Moutal, Laurent F. Martin, Lisa Boinon, Kimberly Gomez, Dongzhi Ran, Yuan Zhou, Harrison J. Stratton, Song Cai, Shizhen Luo, Kerry Beth Gonzalez, Samantha Perez-Miller, Amol Patwardhan, Mohab M. Ibrahim, Rajesh Khanna

Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2’s Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) – a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A–triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A ‘silencing’ of pain via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals. ### Competing Interest Statement R. Khanna is the co-founder of Regulonix LLC, a company developing non-opioids drugs for chronic pain. In addition, R. Khanna has patents US10287334 and US10441586 issued to Regulonix LLC. The other authors declare no competing financial interests. * ACE2 : Angiotensin converting enzyme 2 AUC : area under the curve CaV2.2 : N-type voltage-gated calcium channel COVID-19 : coronavirus disease 2019 DRG : dorsal root ganglia MEA : multi-well microelectrode array NaV1.7 : voltage-gated sodium channel isoform 7 NRP-1 : Neuropilin-1 PWTs : paw withdrawal thresholds SARS-CoV-2 : Severe acute respiratory syndrome coronavirus 2 sEPSCs : spontaneous excitatory postsynaptic currents SNI : spared nerve injury VEGF-A : vascular endothelial growth factor-A

22: Spontaneous behaviors drive multidimensional, brain-wide population activity
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Posted 22 Apr 2018

Spontaneous behaviors drive multidimensional, brain-wide population activity
11,853 downloads bioRxiv neuroscience

Carsen Stringer, Marius Pachitariu, Nicholas A. Steinmetz, Charu Bai Reddy, Matteo Carandini, Kenneth D. Harris

Cortical responses to sensory stimuli are highly variable, and sensory cortex exhibits intricate spontaneous activity even without external sensory input. Cortical variability and spontaneous activity have been variously proposed to represent random noise, recall of prior experience, or encoding of ongoing behavioral and cognitive variables. Here, by recording over 10,000 neurons in mouse visual cortex, we show that spontaneous activity reliably encodes a high-dimensional latent state, which is partially related to the ongoing behavior of the mouse and is represented not just in visual cortex but across the forebrain. Sensory inputs do not interrupt this ongoing signal, but add onto it a representation of visual stimuli in orthogonal dimensions. Thus, visual cortical population activity, despite its apparently noisy structure, reliably encodes an orthogonal fusion of sensory and multidimensional behavioral information.

23: A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality
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Posted 25 Nov 2017

A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality
11,376 downloads bioRxiv neuroscience

Tanya L. Daigle, Linda Madisen, Travis A. Hage, Matthew T. Valley, Ulf Knoblich, Rylan S. Larsen, Marc M Takeno, Lawrence Huang, Hong Gu, Rachael Larsen, Maya Mills, Alice Bosma-Moody, La’Akea Siverts, Miranda Walker, Lucas T Graybuck, Zizhen Yao, Olivia Fong, Emma Garren, Garreck Lenz, Mariya Chavarha, Julie Pendergraft, James Harrington, Karla E. Hirokawa, Julie A. Harris, Medea McGraw, Douglas R. Ollerenshaw, Kimberly A. Smith, Christopher A. Baker, Jonathan T Ting, Susan M. Sunkin, Jerome Lecoq, Michael Z. Lin, Edward S. Boyden, Gabe Murphy, Nuno da Costa, Jack Waters, Lu Li, Bosiljka Tasic, Hongkui Zeng

Modern genetic approaches are powerful in providing access to diverse types of neurons within the mammalian brain and greatly facilitating the study of their function. We here report a large set of driver and reporter transgenic mouse lines, including 23 new driver lines targeting a variety of cortical and subcortical cell populations and 26 new reporter lines expressing an array of molecular tools. In particular, we describe the TIGRE2.0 transgenic platform and introduce Cre-dependent reporter lines that enable optical physiology, optogenetics, and sparse labeling of genetically-defined cell populations. TIGRE2.0 reporters broke the barrier in transgene expression level of single-copy targeted-insertion transgenesis in a wide range of neuronal types, along with additional advantage of a simplified breeding strategy compared to our first-generation TIGRE lines. These novel transgenic lines greatly expand the repertoire of high-precision genetic tools available to effectively identify, monitor, and manipulate distinct cell types in the mouse brain.

24: A Connectome of the Adult Drosophila Central Brain
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Posted 21 Jan 2020

A Connectome of the Adult Drosophila Central Brain
11,064 downloads bioRxiv neuroscience

C. Shan Xu, Michał Januszewski, Zhiyuan Lu, Shin-ya Takemura, Kenneth J. Hayworth, Gary Huang, Kazunori Shinomiya, Jeremy Maitin-Shepard, David Ackerman, Stuart Berg, Tim Blakely, John Bogovic, Jody Clements, Tom Dolafi, Philip M. Hubbard, Dagmar Kainmueller, William T. Katz, Takashi Kawase, Khaled A. Khairy, Laramie Leavitt, Peter H. Li, Larry Lindsey, Nicole L. Neubarth, Donald J. Olbris, Hideo Otsuna, Eric T. Troutman, Lowell Umayam, Ting Zhao, Masayoshi Ito, Jens Goldammer, Tanya Wolff, Robert Svirskas, Philipp Schlegel, Erika R. Neace, Christopher J. Knecht, Chelsea X. Alvarado, Dennis A. Bailey, Samantha Ballinger, Jolanta A Borycz, Brandon S. Canino, Natasha Cheatham, Michael Cook, Marisa Dreher, Octave Duclos, Bryon Eubanks, Kelli Fairbanks, Samantha Finley, Nora Forknall, Audrey Francis, Gary Patrick Hopkins, Emily M. Joyce, SungJin Kim, Nicole A. Kirk, Julie Kovalyak, Shirley A. Lauchie, Alanna Lohff, Charli Maldonado, Emily A. Manley, Sari McLin, Caroline Mooney, Miatta Ndama, Omotara Ogundeyi, Nneoma Okeoma, Christopher Ordish, Nicholas Padilla, Christopher Patrick, Tyler Paterson, Elliott E. Phillips, Emily M. Phillips, Neha Rampally, Caitlin Ribeiro, Madelaine K Robertson, Jon Thomson Rymer, Sean M. Ryan, Megan Sammons, Anne K. Scott, Ashley L. Scott, Aya Shinomiya, Claire Smith, Kelsey Smith, Natalie L. Smith, Margaret A. Sobeski, Alia Suleiman, Jackie Swift, Satoko Takemura, Iris Talebi, Dorota Tarnogorska, Emily Tenshaw, Temour Tokhi, John J. Walsh, Tansy Yang, Jane Anne Horne, Feng Li, Ruchi Parekh, Patricia K. Rivlin, Vivek Jayaraman, Kei Ito, Stephan Saalfeld, Reed George, Ian A. Meinertzhagen, Gerald M. Rubin, Harald F. Hess, Louis Scheffer, Viren Jain, Stephen M. Plaza

The neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions. Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain.

25: Bright and photostable chemigenetic indicators for extended in vivo voltage imaging
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Posted 06 Oct 2018

Bright and photostable chemigenetic indicators for extended in vivo voltage imaging
10,881 downloads bioRxiv neuroscience

Ahmed S. Abdelfattah, Takashi Kawashima, Amrita Singh, Ondrej Novak, Hui Liu, Yichun Shuai, Yi-Chieh Huang, Jonathan B. Grimm, Ronak Patel, Johannes Friedrich, Brett D. Mensh, Liam Paninski, John J Macklin, Kaspar Podgorski, Bei-Jung Lin, Tsai-Wen Chen, Glenn C. Turner, Zhe Liu, Minoru Koyama, Karel Svoboda, Misha B. Ahrens, Luke D. Lavis, Eric R. Schreiter

Imaging changes in membrane potential using genetically encoded fluorescent voltage indicators (GEVIs) has great potential for monitoring neuronal activity with high spatial and temporal resolution. Brightness and photostability of fluorescent proteins and rhodopsins have limited the utility of existing GEVIs. We engineered a novel GEVI, Voltron, that utilizes bright and photostable synthetic dyes instead of protein-based fluorophores, extending the combined duration of imaging and number of neurons imaged simultaneously by more than tenfold relative to existing GEVIs. We used Voltron for in vivo voltage imaging in mice, zebrafish, and fruit flies. In mouse cortex, Voltron allowed single-trial recording of spikes and subthreshold voltage signals from dozens of neurons simultaneously, over 15 minutes of continuous imaging. In larval zebrafish, Voltron enabled the precise correlation of spike timing with behavior.

26: Kilosort: realtime spike-sorting for extracellular electrophysiology with hundreds of channels
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Posted 30 Jun 2016

Kilosort: realtime spike-sorting for extracellular electrophysiology with hundreds of channels
10,817 downloads bioRxiv neuroscience

Marius Pachitariu, Nicholas Steinmetz, Shabnam Kadir, Matteo Carandini, Harris Kenneth D.

Advances in silicon probe technology mean that in vivo electrophysiological recordings from hundreds of channels will soon become commonplace. To interpret these recordings we need fast, scalable and accurate methods for spike sorting, whose output requires minimal time for manual curation. Here we introduce Kilosort, a spike sorting framework that meets these criteria, and show that it allows rapid and accurate sorting of large-scale in vivo data. Kilosort models the recorded voltage as a sum of template waveforms triggered on the spike times, allowing overlapping spikes to be identified and resolved. Rapid processing is achieved thanks to a novel low-dimensional approximation for the spatiotemporal distribution of each template, and to batch-based optimization on GPUs. A novel post-clustering merging step based on the continuity of the templates substantially reduces the requirement for subsequent manual curation operations. We compare Kilosort to an established algorithm on data obtained from 384-channel electrodes, and show superior performance, at much reduced processing times. Data from 384-channel electrode arrays can be processed in approximately realtime. Kilosort is an important step towards fully automated spike sorting of multichannel electrode recordings, and is freely available github.com/cortex-lab/Kilosort.

27: The "sewing machine" for minimally invasive neural recording
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Posted 14 Mar 2019

The "sewing machine" for minimally invasive neural recording
10,591 downloads bioRxiv neuroscience

Timothy L Hanson, Camilo A Diaz-Botia, Viktor Kharazia, Michel M Maharbiz, Philip N Sabes

We present a system for scalable and customizable recording and stimulation of neural activity. In large animals and humans, the current benchmark for high spatial and temporal resolution neural interfaces are fixed arrays of wire or silicon electrodes inserted into the parenchyma of the brain. However, probes that are large and stiff enough to penetrate the brain have been shown to cause acute and chronic damage and inflammation, which limits their longevity, stability, and yield. One approach to this problem is to separate the requirements of the insertion device, which should to be as stiff as possible, with the implanted device, which should be as small and flexible as possible. Here, we demonstrate the feasibility and scalability of this approach with a system incorporating fine and flexible thin-film polymer probes, a fine and stiff insertion needle, and a robotic insertion machine. Together the system permits rapid and precise implantation of probes, each individually targeted to avoid observable vasculature and to attain diverse anatomical targets. As an initial demonstration of this system, we implanted arrays of electrodes in rat somatosensory cortex, recorded extracellular action potentials from them, and obtained histological images of the tissue response. This approach points the way toward a new generation of scaleable, stable, and safe neural interfaces, both for the basic scientific study of brain function and for clinical applications.

28: Widespread and targeted gene expression by systemic AAV vectors: Production, purification, and administration
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Posted 11 Jan 2018

Widespread and targeted gene expression by systemic AAV vectors: Production, purification, and administration
10,579 downloads bioRxiv neuroscience

Rosemary C Challis, Sripriya Ravindra Kumar, Ken Y Chan, Collin Challis, Min J Jang, Pradeep S Rajendran, John D Tompkins, Kalyanam Shivkumar, Benjamin E. Deverman, Viviana Gradinaru

We recently developed novel AAV capsids for efficient and noninvasive gene transfer across the central and peripheral nervous systems. In this protocol, we describe how to produce and systemically administer AAV-PHP viruses to label and/or genetically manipulate cells in the mouse nervous system and organs including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans eight days, excluding the time required to assess gene expression, and can be readily adopted by laboratories with standard molecular and cell culture capabilities. We provide guidelines for experimental design and choosing the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing.

29: Automated Reconstruction of a Serial-Section EM Drosophila Brain with Flood-Filling Networks and Local Realignment
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Posted 11 Apr 2019

Automated Reconstruction of a Serial-Section EM Drosophila Brain with Flood-Filling Networks and Local Realignment
9,946 downloads bioRxiv neuroscience

Peter H. Li, Larry F. Lindsey, Michał Januszewski, Zhihao Zheng, Alexander Shakeel Bates, István Taisz, Mike Tyka, Matthew Nichols, Feng Li, Eric Perlman, Jeremy Maitin-Shepard, Tim Blakely, Laramie Leavitt, Gregory S.X.E. Jefferis, Davi Bock, Viren Jain

Reconstruction of neural circuitry at single-synapse resolution is a key target for improving understanding of the nervous system in health and disease. Serial section transmission electron microscopy (ssTEM) is among the most prolific imaging methods employed in pursuit of such reconstructions. We demonstrate how Flood-Filling Networks (FFNs) can be used to computationally segment a forty-teravoxel whole-brain Drosophila ssTEM volume. To compensate for data irregularities and imperfect global alignment, FFNs were combined with procedures that locally re-align serial sections and dynamically adjust image content. The proposed approach produced a largely merger-free segmentation of the entire ssTEM Drosophila brain, which we make freely available. As compared to manual tracing using an efficient skeletonization strategy, the segmentation enabled circuit reconstruction and analysis workflows that were an order of magnitude faster. ### Competing Interest Statement The authors have declared no competing interest.

30: Molecular architecture of the mouse nervous system
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Posted 05 Apr 2018

Molecular architecture of the mouse nervous system
9,913 downloads bioRxiv neuroscience

Amit Zeisel, Hannah Hochgerner, Peter Lönnerberg, Anna Johnsson, Fatima Memic, Job van der Zwan, Martin Häring, Emelie Braun, Lars E. Borm, Gioele La Manno, Simone Codeluppi, Alessandro Furlan, N. G. Skene, Kenneth D. Harris, Jens Hjerling-Leffler, Ernest Arenas, Patrik Ernfors, Ulrika Marklund, Sten Linnarsson

The mammalian nervous system executes complex behaviors controlled by specialised, precisely positioned and interacting cell types. Here, we used RNA sequencing of half a million single cells to create a detailed census of cell types in the mouse nervous system. We mapped cell types spatially and derived a hierarchical, data-driven taxonomy. Neurons were the most diverse, and were grouped by developmental anatomical units, and by the expression of neurotransmitters and neuropeptides. Neuronal diversity was driven by genes encoding cell identity, synaptic connectivity, neurotransmission and membrane conductance. We discovered several distinct, regionally restricted, astrocytes types, which obeyed developmental boundaries and correlated with the spatial distribution of key glutamate and glycine neurotransmitters. In contrast, oligodendrocytes showed a loss of regional identity, followed by a secondary diversi cation. The resource presented here lays a solid foundation for understanding the molecular architecture of the mammalian nervous system, and enables genetic manipulation of specific cell types.

31: A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain
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Posted 10 Apr 2018

A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain
9,820 downloads bioRxiv neuroscience

Arpiar Saunders, Evan Z. Macosko, Alec Wysoker, Melissa Goldman, Fenna Krienen, Heather de Rivera, Elizabeth Bien, Matthew Baum, Shuyu Wang, Aleks Goeva, James Nemesh, Nolan Kamitaki, Sara Brumbaugh, David Kulp, Steven A McCarroll

The mammalian brain is composed of diverse, specialized cell populations, few of which we fully understand. To more systematically ascertain and learn from cellular specializations in the brain, we used Drop-seq to perform single-cell RNA sequencing of 690,000 cells sampled from nine regions of the adult mouse brain: frontal and posterior cortex (156,000 and 99,000 cells, respectively), hippocampus (113,000), thalamus (89,000), cerebellum (26,000), and all of the basal ganglia - the striatum (77,000), globus pallidus externus/nucleus basalis (66,000), entopeduncular/subthalamic nuclei (19,000), and the substantia nigra/ventral tegmental area (44,000). We developed computational approaches to distinguish biological from technical signals in single-cell data, then identified 565 transcriptionally distinct groups of cells, which we annotate and present through interactive online software we developed for visualizing and re-analyzing these data (DropViz). Comparison of cell classes and types across regions revealed features of brain organization. These included a neuronal gene-expression module for synthesizing axonal and presynaptic components; widely shared patterns in the combinatorial co-deployment of voltage-gated ion channels by diverse neuronal populations; functional distinctions among cells of the brain vasculature; and specialization of glutamatergic neurons across cortical regions to a degree not observed in other neuronal or non-neuronal populations. We describe systematic neuronal classifications for two complex, understudied regions of the basal ganglia, the globus pallidus externus and substantia nigra reticulata. In the striatum, where neuron types have been intensely researched, our data reveal a previously undescribed population of striatal spiny projection neurons (SPNs) comprising 4% of SPNs. The adult mouse brain cell atlas can serve as a reference for analyses of development, disease, and evolution.

32: Nested oscillatory dynamics in cortical organoids model early human brain network development
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Posted 29 Jun 2018

Nested oscillatory dynamics in cortical organoids model early human brain network development
9,524 downloads bioRxiv neuroscience

Cleber A. Trujillo, Richard D. Gao, Priscilla D. Negraes, Isaac A. Chaim, Alain Domissy, Matthieu Vandenberghe, Anna Devor, Gene W Yeo, Bradley Voytek, Alysson R. Muotri

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we analyzed cortical organoids that spontaneously developed periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our model provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.

33: A computational toolbox and step-by-step tutorial for the analysis of neuronal population dynamics in calcium imaging data
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Posted 28 Jan 2017

A computational toolbox and step-by-step tutorial for the analysis of neuronal population dynamics in calcium imaging data
9,155 downloads bioRxiv neuroscience

Sebastián A. Romano, Verónica Pérez-Schuster, Adrien Jouary, Alessia Candeo, Jonathan Boulanger-Weill, Germán Sumbre

The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a tutorial for the use of a comprehensive computational toolbox for the analysis of neuronal population activity imaging. It consists of tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. They are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets, and provide a case study to explain its implementation.

34: High-dimensional geometry of population responses in visual cortex
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Posted 22 Jul 2018

High-dimensional geometry of population responses in visual cortex
9,129 downloads bioRxiv neuroscience

Carsen Stringer, Marius Pachitariu, Nicholas A. Steinmetz, Matteo Carandini, Kenneth D. Harris

A neuronal population encodes information most efficiently when its activity is uncorrelated and high-dimensional, and most robustly when its activity is correlated and lower-dimensional. Here, we analyzed the correlation structure of natural image coding, in large visual cortical populations recorded from awake mice. Evoked population activity was high dimensional, with correlations obeying an unexpected power-law: the n-th principal component variance scaled as 1/n. This was not inherited from the 1/f spectrum of natural images, because it persisted after stimulus whitening. We proved mathematically that the variance spectrum must decay at least this fast if a population code is smooth, i.e. if small changes in input cannot dominate population activity. The theory also predicts larger power-law exponents for lower-dimensional stimulus ensembles, which we validated experimentally. These results suggest that coding smoothness represents a fundamental constraint governing correlations in neural population codes.

35: Enhancer viruses and a transgenic platform for combinatorial cell subclass-specific labeling
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Posted 20 Jan 2019

Enhancer viruses and a transgenic platform for combinatorial cell subclass-specific labeling
8,961 downloads bioRxiv neuroscience

Lucas T Graybuck, Tanya L. Daigle, Adriana E. Sedeño-Cortés, Miranda Walker, Brian E. Kalmbach, Garreck H. Lenz, Thuc Nghi Nguyen, Emma Garren, Tae Kyung Kim, La’ Akea Siverts, Jacqueline L. Bendrick, Thomas Zhou, Marty Mortrud, Shenqin Yao, Ali Cetin, Rachael Larsen, Luke Esposito, Bryan Gore, Eric Szelenyi, Elyse Morin, John K. Mich, Nick Dee, Jeff Goldy, Kimberly A. Smith, Zizhen Yao, Viviana Gradinaru, Susan M. Sunkin, Ed Lein, Boaz P. Levi, Jonathan T Ting, Hongkui Zeng, Bosiljka Tasic

The rapid pace of cell type identification by new single-cell analysis methods has not been met with efficient experimental access to the newly discovered types. To enable flexible and efficient access to specific neural populations in the mouse cortex, we collected chromatin accessibility data from individual cells and clustered the single-cell data to identify enhancers specific for cell classes and subclasses. When cloned into adeno-associated viruses (AAVs) and delivered to the brain by retro-orbital injections, these enhancers drive transgene expression in specific cell subclasses in the cortex. We characterize several enhancer viruses in detail to show that they result in labeling of different projection neuron subclasses in mouse cortex, and that one of them can be used to label the homologous projection neuron subclass in human cortical slices. To enable the combinatorial labeling of more than one cell type by enhancer viruses, we developed a three-color Cre-, Flp- and Nigri- recombinase dependent reporter mouse line, Ai213. The delivery of three enhancer viruses driving these recombinases via a single retroorbital injection into a single Ai213 transgenic mouse results in labeling of three different neuronal classes/subclasses in the same brain tissue. This approach combines unprecedented flexibility with specificity for investigation of cell types in the mouse brain and beyond. ### Competing Interest Statement The authors have declared no competing interest.

36: A better way to define and describe Morlet wavelets for time-frequency analysis
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Posted 21 Aug 2018

A better way to define and describe Morlet wavelets for time-frequency analysis
8,954 downloads bioRxiv neuroscience

Mike X Cohen

Morlet wavelets are frequently used for time-frequency analysis of non-stationary time series data, such as neuroelectrical signals recorded from the brain. The crucial parameter of Morlet wavelets is the width of the Gaussian that tapers the sine wave. This width parameter controls the trade-off between temporal precision and frequency precision. It is typically defined as the "number of cycles," but this parameter is opaque, and often leads to uncertainty and suboptimal analysis choices, as well as being difficult to interpret and evaluate. The purpose of this paper is to present alternative formulations of Morlet wavelets in time and in frequency that allow parameterizing the wavelets directly in terms of the desired temporal and spectral smoothing (as full-width at half-maximum). This formulation provides clarity on an important data analysis parameter, and should facilitate proper analyses, reporting, and interpretation of results. MATLAB code is provided.

37: Distinguishing between parallel and serial processing in visual attention from neurobiological data
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Posted 02 Aug 2018

Distinguishing between parallel and serial processing in visual attention from neurobiological data
8,775 downloads bioRxiv neuroscience

Kang Li, Mikiko Kadohisa, Makoto Kusunoki, John Duncan, Claus Bundesen, Susanne Ditlevsen

Serial and parallel processing in visual search have been long debated in psychology but the processing mechanism remains an open issue. Serial processing allows only one object at a time to be processed, whereas parallel processing assumes that various objects are processed simultaneously. Here we present novel neural models for the two types of processing mechanisms based on analysis of simultaneously recorded spike trains using electrophysiological data from prefrontal cortex of rhesus monkeys while processing task-relevant visual displays. We combine mathematical models describing neuronal attention and point process models for spike trains. The same model can explain both serial and parallel processing by adopting different parameter regimes. We present statistical methods to distinguish between serial and parallel processing based on both maximum likelihood estimates and decoding analysis of the attention when two stimuli are presented simultaneously. Results show that both processing mechanisms are in play for the simultaneously recorded neurons, but neurons tend to follow parallel processing in the beginning after the onset of the stimulus pair, whereas they tend to serial processing later on. This could be explained by parallel processing being related to sensory bottom-up signals or feedforward processing, which typically occur in the beginning after stimulus onset, whereas top-down signals related to cognitive modulatory influences guiding attentional effects in recurrent feedback connections occur after a small delay, and is related to serial processing, where all processing capacities are being directed towards the attended object.

38: Modern machine learning outperforms GLMs at predicting spikes
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Posted 24 Feb 2017

Modern machine learning outperforms GLMs at predicting spikes
8,738 downloads bioRxiv neuroscience

Ari S. Benjamin, Hugo L. Fernandes, Tucker Tomlinson, Pavan Ramkumar, Chris VerSteeg, Raeed Chowdhury, Lee Miller, Konrad P Kording

Neuroscience has long focused on finding encoding models that effectively ask "what predicts neural spiking?" and generalized linear models (GLMs) are a typical approach. It is often unknown how much of explainable neural activity is captured, or missed, when fitting a GLM. Here we compared the predictive performance of GLMs to three leading machine learning methods: feedforward neural networks, gradient boosted trees (using XGBoost), and stacked ensembles that combine the predictions of several methods. We predicted spike counts in macaque motor (M1) and somatosensory (S1) cortices from standard representations of reaching kinematics, and in rat hippocampal cells from open field location and orientation. In general, the modern methods (particularly XGBoost and the ensemble) produced more accurate spike predictions and were less sensitive to the preprocessing of features. This discrepancy in performance suggests that standard feature sets may often relate to neural activity in a nonlinear manner not captured by GLMs. Encoding models built with machine learning techniques, which can be largely automated, more accurately predict spikes and can offer meaningful benchmarks for simpler models.

39: A neural algorithm for a fundamental computing problem
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Posted 25 Aug 2017

A neural algorithm for a fundamental computing problem
8,687 downloads bioRxiv neuroscience

Sanjoy Dasgupta, Charles F Stevens, Saket Navlakha

Similarity search, such as identifying similar images in a database or similar documents on the Web, is a fundamental computing problem faced by many large-scale information retrieval systems. We discovered that the fly's olfactory circuit solves this problem using a novel variant of a traditional computer science algorithm (called locality-sensitive hashing). The fly's circuit assigns similar neural activity patterns to similar input stimuli (odors), so that behaviors learned from one odor can be applied when a similar odor is experienced. The fly's algorithm, however, uses three new computational ingredients that depart from traditional approaches. We show that these ingredients can be translated to improve the performance of similarity search compared to traditional algorithms when evaluated on several benchmark datasets. Overall, this perspective helps illuminate the logic supporting an important sensory function (olfaction), and it provides a conceptually new algorithm for solving a fundamental computational problem.

40: Parameterizing neural power spectra
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Posted 11 Apr 2018

Parameterizing neural power spectra
8,565 downloads bioRxiv neuroscience

Matar Haller, Thomas Donoghue, Erik Peterson, Paroma Varma, Priyadarshini Sebastian, Richard D. Gao, Torben Noto, Robert T Knight, Avgusta Shestyuk, Bradley Voytek

Electrophysiological signals across species and recording scales exhibit both periodic and aperiodic features. Periodic oscillations have been widely studied and linked to numerous physiological, cognitive, behavioral, and disease states, while the aperiodic "background" 1/f component of neural power spectra has received far less attention. Most analyses of oscillations are conducted on a priori, canonically-defined frequency bands without consideration of the underlying aperiodic structure, or verification that a periodic signal even exists in addition to the aperiodic signal. This is problematic, as recent evidence shows that the aperiodic signal is dynamic, changing with age, task demands, and cognitive state. It has also been linked to the relative excitation/inhibition of the underlying neuronal population. This means that standard analytic approaches easily conflate changes in the periodic and aperiodic signals with one another because the aperiodic parameters--along with oscillation center frequency, power, and bandwidth--are all dynamic in physiologically meaningful, but likely different, ways. In order to overcome the limitations of traditional narrowband analyses and to reduce the potentially deleterious effects of conflating these features, we introduce a novel algorithm for automatic parameterization of neural power spectral densities (PSDs) as a combination of the aperiodic signal and putative periodic oscillations. Notably, this algorithm requires no a priori specification of band limits and accounts for potentially-overlapping oscillations while minimizing the degree to which they are confounded with one another. This algorithm is amenable to large-scale data exploration and analysis, providing researchers with a tool to quickly and accurately parameterize neural power spectra.

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