scholarly journals E-Cannula reveals anatomical diversity in sharp-wave ripples as a driver for the recruitment of distinct hippocampal assemblies

2021 ◽  
Author(s):  
Xin Liu ◽  
Satoshi Terada ◽  
Jeonghoon Kim ◽  
Yichen Lu ◽  
Mehrdad Ramezani ◽  
...  
Keyword(s):  
Large Scale ◽  
Critical Role ◽  
Population Level ◽  
Technical Difficulty ◽  
Brain Regions ◽  
Cell Assemblies ◽  
Sharp Wave ◽  
Wave Patterns ◽  
Scale Population

The hippocampus plays a critical role in spatial navigation and episodic memory. However, research on in vivo hippocampal activity dynamics has mostly relied on single modalities such as electrical recordings or optical imaging, with respectively limited spatial and temporal resolution. This technical difficulty greatly impedes multi-level investigations into network state-related changes in cellular activity. To overcome these limitations, we developed the E-Cannula integrating fully transparent graphene microelectrodes with imaging-cannula. The E-Cannula enables the simultaneous electrical recording and two-photon calcium imaging from the exact same population of neurons across an anatomically extended region of the mouse hippocampal CA1 stably across several days. These large-scale simultaneous optical and electrical recordings showed that local hippocampal sharp wave ripples (SWRs) are associated with synchronous calcium events involving large neural populations in CA1. We show that SWRs exhibit spatiotemporal wave patterns along multiple axes in 2D space with different spatial extents (local or global) and temporal propagation modes (stationary or travelling). Notably, distinct SWR wave patterns were associated with, and decoded from, the selective recruitment of orthogonal CA1 cell assemblies. These results suggest that the diversity in the anatomical progression of SWRs may serve as a mechanism for the selective activation of the unique hippocampal cell assemblies extensively implicated in the encoding of distinct memories. Through these results we demonstrate the utility of the E-Cannula as a versatile neurotechnology with the potential for future integration with other optical components such as green lenses, fibers or prisms enabling the multi-modal investigation of cross-time scale population-level neural dynamics across brain regions.

scholarly journals Nonlinear visuoauditory integration in the mouse superior colliculus

2021 ◽  
Author(s):  
Shinya Ito ◽  
Yufei Si ◽  
Alan M. Litke ◽  
David A. Feldheim
Keyword(s):  
Superior Colliculus ◽  
Sensory Integration ◽  
Large Scale ◽  
Temporal Dynamics ◽  
Critical Role ◽  
Sensory Information ◽  
Population Level ◽  
Object Identification ◽  
Response Properties ◽  
The Individual

AbstractSensory information from different modalities is processed in parallel, and then integrated in associative brain areas to improve object identification and the interpretation of sensory experiences. The Superior Colliculus (SC) is a midbrain structure that plays a critical role in integrating visual, auditory, and somatosensory input to assess saliency and promote action. Although the response properties of the individual SC neurons to visuoauditory stimuli have been characterized, little is known about the spatial and temporal dynamics of the integration at the population level. Here we recorded the response properties of SC neurons to spatially restricted visual and auditory stimuli using large-scale electrophysiology. We then created a general, population-level model that explains the spatial, temporal, and intensity requirements of stimuli needed for sensory integration. We found that the mouse SC contains topographically organized visual and auditory neurons that exhibit nonlinear multisensory integration. We show that nonlinear integration depends on properties of auditory but not visual stimuli. We also find that a heuristically derived nonlinear modulation function reveals conditions required for sensory integration that are consistent with previously proposed models of sensory integration such as spatial matching and the principle of inverse effectiveness.

scholarly journals Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus upon infusion of [U-13C6]glucose

2020 ◽  
pp. 0271678X2091053
Author(s):  
Antoine Cherix ◽  
Guillaume Donati ◽  
Blanca Lizarbe ◽  
Bernard Lanz ◽  
Carole Poitry-Yamate ◽  
...  
Keyword(s):  
Critical Role ◽  
Tca Cycle ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Resonance Spectroscopy ◽  
Spectral Fitting ◽  
Mouse Hippocampus ◽  
And Behavior ◽  
Gabaergic Activity

Hippocampus plays a critical role in linking brain energetics and behavior typically associated to stress exposure. In this study, we aimed to simultaneously assess excitatory and inhibitory neuronal metabolism in mouse hippocampus in vivo by applying 18FDG-PET and indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) at 14.1 T upon infusion of uniformly 13C-labeled glucose ([U-13C6]Glc). Improving the spectral fitting by taking into account variable decoupling efficiencies of [U-13C6]Glc and refining the compartmentalized model by including two γ-aminobutyric acid (GABA) pools permit us to evaluate the relative contributions of glutamatergic and GABAergic metabolism to total hippocampal neuroenergetics. We report that GABAergic activity accounts for ∼13% of total neurotransmission (VNT) and ∼27% of total neuronal TCA cycle (VTCA) in mouse hippocampus suggesting a higher VTCA/VNT ratio for inhibitory neurons compared to excitatory neurons. Finally, our results provide new strategies and tools for bringing forward the developments and applications of 13C-MRS in specific brain regions of small animals.

scholarly journals Large-Scale Chronically Implantable Precision Motorized Microdrive Array for Freely Behaving Animals

2008 ◽  
Vol 100 (4) ◽  
pp. 2430-2440 ◽  
Author(s):  
Jun Yamamoto ◽  
Matthew A. Wilson
Keyword(s):  
Single Unit ◽  
Large Scale ◽  
Neural Circuits ◽  
Brain Regions ◽  
Unit Recording ◽  
Chronic Recording ◽  
Large Numbers ◽  
Freely Behaving

Multiple single-unit recording has become one of the most powerful in vivo electro-physiological techniques for studying neural circuits. The demand has been increasing for small and lightweight chronic recording devices that allow fine adjustments to be made over large numbers of electrodes across multiple brain regions. To achieve this, we developed precision motorized microdrive arrays that use a novel motor multiplexing headstage to dramatically reduce wiring while preserving precision of the microdrive control. Versions of the microdrive array were chronically implanted on both rats (21 microdrives) and mice (7 microdrives), and relatively long-term recordings were taken.

scholarly journals Nucleosomes impede Cas9 access to DNA in vivo and in vitro

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Max A Horlbeck ◽  
Lea B Witkowsky ◽  
Benjamin Guglielmi ◽  
Joseph M Replogle ◽  
Luke A Gilbert ◽  
...  
Keyword(s):  
Large Scale ◽  
Nucleosome Occupancy ◽  
Critical Role ◽  
Genetic Screens ◽  
Guide Rnas ◽  
Highly Active ◽  
Bacterial Enzyme ◽  
Eukaryotic Chromatin

The prokaryotic CRISPR (clustered regularly interspaced palindromic repeats)-associated protein, Cas9, has been widely adopted as a tool for editing, imaging, and regulating eukaryotic genomes. However, our understanding of how to select single-guide RNAs (sgRNAs) that mediate efficient Cas9 activity is incomplete, as we lack insight into how chromatin impacts Cas9 targeting. To address this gap, we analyzed large-scale genetic screens performed in human cell lines using either nuclease-active or nuclease-dead Cas9 (dCas9). We observed that highly active sgRNAs for Cas9 and dCas9 were found almost exclusively in regions of low nucleosome occupancy. In vitro experiments demonstrated that nucleosomes in fact directly impede Cas9 binding and cleavage, while chromatin remodeling can restore Cas9 access. Our results reveal a critical role of eukaryotic chromatin in dictating the targeting specificity of this transplanted bacterial enzyme, and provide rules for selecting Cas9 target sites distinct from and complementary to those based on sequence properties.

scholarly journals Reliability of the NIH toolbox cognitive battery in children and adolescents: a 3-year longitudinal examination

2020 ◽  
pp. 1-10
Author(s):  
Brittany K. Taylor ◽  
Michaela R. Frenzel ◽  
Jacob A. Eastman ◽  
Alex I. Wiesman ◽  
Yu-Ping Wang ◽  
...  
Keyword(s):  
Large Scale ◽  
Intraclass Correlation ◽  
Temporal Stability ◽  
Correlation Coefficients ◽  
Population Level ◽  
Clinical Applications ◽  
Intraclass Correlation Coefficients ◽  
Scale Population ◽  
Longitudinal Examination

Abstract Background The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth. Methods The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years. Results Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other. Conclusions Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.

Learnings from Large-Scale, Population-Level Implementation of Parenting Support

2017 ◽  
pp. 419-421
Author(s):  
Trevor G. Mazzucchelli
Keyword(s):  
Large Scale ◽  
Best Practice ◽  
Systems Approach ◽  
Positive Impact ◽  
Population Level ◽  
The United States ◽  
Parenting Support ◽  
Scale Population ◽  
The Many ◽  
Learning Principles

There is considerable evidence supporting the efficacy and effectiveness of parenting interventions based on social learning principles for a range of social, emotional, and health problems, involving different types of families and through a variety of delivery systems. The challenge now is “going to scale” in order to have a positive impact at a population level. This chapter introduces three best practice exemplars that have taken place in the United States, Ireland, and Australia, where a full multilevel systems approach to parenting support has been applied and evaluated. These applications provide important lessons regarding the barriers and facilitators that can influence an initiative’s success and degree of impact. By illustrating how these approaches have involved different populations, behavioral targets, evaluation designs, and means of assessing outcome, they also hint at the many possibilities that are available in future dissemination efforts.

scholarly journals Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

2020 ◽  
Vol 38 (S1) ◽  
pp. 72-90 ◽  
Author(s):  
Niels Nijsingh ◽  
Christian Munthe ◽  
Anna Lindblom ◽  
Christina Åhrén
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Large Scale ◽  
Population Level ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Screening Programs ◽  
Scale Population ◽  
Current Screening

AbstractEffectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention’s effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised.

scholarly journals Nuclear RNA-seq of single neurons reveals molecular signatures of activation

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Benjamin Lacar ◽  
Sara B. Linker ◽  
Baptiste N. Jaeger ◽  
Suguna Rani Krishnaswami ◽  
Jerika J. Barron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Large Scale ◽  
Granule Cells ◽  
Mapk Pathway ◽  
Cell Types ◽  
Brain Regions ◽  
Activation Patterns ◽  
Environment Exposure

Abstract Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos, Arc and Egr1. SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes. In addition, we observe a continuum of activation states, revealing a pseudotemporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs, allowing for novel insights into neuronal activation patterns in vivo.

scholarly journals Refinement of corticospinal neuron activity during skilled motor learning

2021 ◽  
Author(s):  
Najet Serradj ◽  
Francesca Marino ◽  
Yunuen Moreno-López ◽  
Sydney Agger ◽  
Andrew Sloan ◽  
...  
Keyword(s):  
Large Scale ◽  
Primary Motor Cortex ◽  
Corticospinal Tract ◽  
Activity Patterns ◽  
Critical Role ◽  
Network Activity ◽  
Neuron Activity ◽  
Cortical Motor ◽  
Dependent Behavior

AbstractThe learning of motor skills relies on plasticity of the primary motor cortex as task acquisition drives the remodeling of cortical motor networks1,2. Large scale cortical remodeling of evoked motor outputs occurs in response to the learning of skilled, corticospinal-dependent behavior, but not simple, unskilled tasks1. Here we determine the response of corticospinal neurons to both skilled and unskilled motor training and assess the role of corticospinal neuron activity in the execution of the trained behaviors. Using in vivo calcium imaging, we found that refinement of corticospinal activity correlated with the development of skilled, but not unskilled, motor expertise. Animals that failed to learn our skilled task exhibited a limited repertoire of dynamic movements and a corresponding absence of network modulation. Transection of the corticospinal tract and aberrant activation of corticospinal neurons show the necessity for corticospinal network activity patterns in the execution of skilled, but not unskilled, movement. We reveal a critical role for corticospinal network modulation in the learning and execution of skilled motor movements. The integrity of the corticospinal tract is essential to the recovery of voluntary movement after central nervous system injuries and these findings should help to shape translational approaches to motor recovery.

scholarly journals Origin of Slow Spontaneous Resting-State Neuronal Fluctuations in Brain Networks

2017 ◽  
Author(s):  
Giri P. Krishnan ◽  
Oscar C. González ◽  
Maxim Bazhenov
Keyword(s):  
Computational Model ◽  
Resting State ◽  
Large Scale ◽  
Brain Activity ◽  
Brain Regions ◽  
Brain Network ◽  
Ion Concentration ◽  
Brain State ◽  
The Brain

AbstractResting or baseline state low frequency (0.01-0.2 Hz) brain activity has been observed in fMRI, EEG and LFP recordings. These fluctuations were found to be correlated across brain regions, and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (< 0.05 Hz) fluctuations could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra and extracellular K+ and Na+ and intracellular Cl- ions, Na+/K+ exchange pump, and KCC2 co-transporter. In the network model representing resting awake-like brain state, we observed slow fluctuations in the extracellular K+ concentration, Na+/K+ pump activation, firing rate of neurons and local field potentials. Holding K+ concentration constant prevented generation of these fluctuations. The amplitude and peak frequency of this activity were modulated by Na+/K+ pump, AMPA/GABA synaptic currents and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state networks observed in vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are observed as the resting-state fluctuations in fMRI and EEG recordings.

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