scholarly journals Heterogeneous Associative Plasticity in the Auditory Cortex Induced by Fear Learning – Novel Insight Into the Classical Conditioning Paradigm

2021 ◽  
pp. 447-460
Author(s):  
O ZELENKA ◽  
O NOVAK ◽  
A BRUNOVA ◽  
J SYKA
Keyword(s):  
Auditory Cortex ◽  
Single Cell ◽  
Escape Behavior ◽  
Stimulus Frequency ◽  
Fear Learning ◽  
Conditioning Paradigm ◽  
Two Photon ◽  
Simple Expansion ◽  
Insight Into ◽  
Conventional Freezing

We used two-photon calcium imaging with single-cell and cell-type resolution. Fear conditioning induced heterogeneous tuning shifts at single-cell level in the auditory cortex, with shifts both to CS+ frequency and to the control CS- stimulus frequency. We thus extend the view of simple expansion of CS+ tuned regions. Instead of conventional freezing reactions only, we observe selective orienting responses towards the conditioned stimuli. The orienting responses were often followed by escape behavior.

scholarly journals Network dynamics underlying OFF responses in the auditory cortex

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Giulio Bondanelli ◽  
Thomas Deneux ◽  
Brice Bathellier ◽  
Srdjan Ostojic
Keyword(s):  
Auditory Cortex ◽  
Single Cell ◽  
Cell Model ◽  
Network Models ◽  
Population Responses ◽  
Two Photon ◽  
Cortical Areas ◽  
Single Cell Model ◽  
Spatio Temporal ◽  
Low Dimensional

Across sensory systems, complex spatio-temporal patterns of neural activity arise following the onset (ON) and offset (OFF) of stimuli. While ON responses have been widely studied, the mechanisms generating OFF responses in cortical areas have so far not been fully elucidated. We examine here the hypothesis that OFF responses are single-cell signatures of recurrent interactions at the network level. To test this hypothesis, we performed population analyses of two-photon calcium recordings in the auditory cortex of awake mice listening to auditory stimuli, and compared linear single-cell and network models. While the single-cell model explained some prominent features of the data, it could not capture the structure across stimuli and trials. In contrast, the network model accounted for the low-dimensional organisation of population responses and their global structure across stimuli, where distinct stimuli activated mostly orthogonal dimensions in the neural state-space.

scholarly journals Contextual fear learning and memory differ between stress coping styles in zebrafish

2019 ◽  
Author(s):  
Matthew R Baker ◽  
Ryan Y Wong
Keyword(s):  
Learning And Memory ◽  
Coping Style ◽  
Coping Styles ◽  
Fear Learning ◽  
Stress Coping ◽  
Conditioning Paradigm ◽  
Contextual Fear ◽  
Reactive Stress ◽  
Stress Coping Strategies ◽  
Insight Into

AbstractAnimals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individual’s survival. As part of an animal’s stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a natural olfactory alarm cue. Our results show that both proactive and reactive zebrafish learn and remember this fearful association. However, we note significant interaction effects between stress coping style and cognition. Zebrafish with the reactive stress coping style acquired the fear memory at a significantly faster rate than proactive fish. While both stress coping styles showed equal memory recall one day post-training, reactive zebrafish showed significantly stronger recall of the conditioned context relative to proactive fish four days post-training. Through understanding how stress coping strategies promote biases in processing salient information, we gain insight into mechanisms that can constrain adaptive behavioral responses.

scholarly journals Network dynamics underlying OFF responses in the auditory cortex

2019 ◽  
Author(s):  
Giulio Bondanelli ◽  
Thomas Deneux ◽  
Brice Bathellier ◽  
Srdjan Ostojic
Keyword(s):  
Auditory Cortex ◽  
Single Cell ◽  
Network Model ◽  
Network Dynamics ◽  
Population Responses ◽  
Two Photon ◽  
Cortical Areas ◽  
Population Analyses ◽  
Spatio Temporal ◽  
Low Dimensional

AbstractAcross sensory systems, complex spatio-temporal patterns of neural activity arise following the onset (ON) and offset (OFF) of stimuli. While ON responses have been widely studied, the mechanisms generating OFF responses in cortical areas have so far not been fully elucidated. We examine here the hypothesis that OFF responses are single-cell signatures of network dynamics and propose a network model that generates transient OFF responses through recurrent interactions. To test this model, we performed population analyses of two-photon calcium recordings in the auditory cortex of awake mice listening to auditory stimuli. We found that the network model accounts for the low-dimensional organisation of population responses and their global structure across stimuli, where distinct stimuli activate mostly orthogonal dimensions in the neural state-space. In contrast, a single-cell mechanism explains some prominent features of the data, but does not account for the structure across stimuli and trials captured by the network model.

scholarly journals Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vidya C. Sinha ◽  
Amanda L. Rinkenbaugh ◽  
Mingchu Xu ◽  
Xinhui Zhou ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Mouse Model ◽  
Transition State ◽  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Breast Lesions ◽  
Aggressive Tumor ◽  
Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

scholarly journals Single Cell Atlas of Human Dura Reveals Cellular Meningeal Landscape and Insights into Meningioma Immune Response

2021 ◽  
Author(s):  
Anthony Z Wang ◽  
Jay Bowman-Kirigin ◽  
Rupen Desai ◽  
Pujan Patel ◽  
Bhuvic Patel ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Copy Number Variant ◽  
Cell Types ◽  
Cell Receptor ◽  
Immune Microenvironment ◽  
Clinical Models ◽  
Insight Into

Recent investigation of the meninges, specifically the dura layer, has highlighted its importance in CNS immune surveillance beyond a purely structural role. However, most of our understanding of the meninges stems from the use of pre-clinical models rather than human samples. In this study, we use single cell RNA-sequencing to perform the first characterization of both non-tumor-associated human dura and meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, through T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. We also identify a functionally heterogeneous population of non-immune cell types and report copy-number variant heterogeneity within our meningioma samples. Our comprehensive investigation of both the immune and non-immune cell landscapes of human dura and meningioma at a single cell resolution provide new insight into previously uncharacterized roles of human dura.

scholarly journals Panoramic stitching of heterogeneous single-cell transcriptomic data

2018 ◽  
Author(s):  
Brian Hie ◽  
Bryan Bryson ◽  
Bonnie Berger
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Data Sets ◽  
Cell Type ◽  
Data Set ◽  
Wide Range ◽  
Data Set Integration ◽  
Biological Patterns ◽  
Insight Into ◽  
Comprehensive Reference

AbstractResearchers are generating single-cell RNA sequencing (scRNA-seq) profiles of diverse biological systems1–4 and every cell type in the human body.5 Leveraging this data to gain unprecedented insight into biology and disease will require assembling heterogeneous cell populations across multiple experiments, laboratories, and technologies. Although methods for scRNA-seq data integration exist6,7, they often naively merge data sets together even when the data sets have no cell types in common, leading to results that do not correspond to real biological patterns. Here we present Scanorama, inspired by algorithms for panorama stitching, that overcomes the limitations of existing methods to enable accurate, heterogeneous scRNA-seq data set integration. Our strategy identifies and merges the shared cell types among all pairs of data sets and is orders of magnitude faster than existing techniques. We use Scanorama to combine 105,476 cells from 26 diverse scRNA-seq experiments across 9 different technologies into a single comprehensive reference, demonstrating how Scanorama can be used to obtain a more complete picture of cellular function across a wide range of scRNA-seq experiments.

Discovery and Insight into One-photon and Two-photon Excited ACQ-to-AIE Conversion via Positional Isomerization

2021 ◽  
Author(s):  
Xueting Long ◽  
Jieyu Wu ◽  
Sirui Yang ◽  
Ziqi Deng ◽  
Yusen Zheng ◽  
...  
Keyword(s):  
Positional Isomers ◽  
Two Photon ◽  
Positional Isomerization ◽  
Aggregation Behaviors ◽  
Insight Into

Two positional isomers (regioisomers) through changing the substituted position of perylenetetracarboxylic diimide and benzanthrone moieties were designed and synthesized. These two regioisomers exhibit totally different aggregation behaviors. The meta (bay)-substituted...

scholarly journals Single cell analysis of the developing mouse kidney provides deeper insight into marker gene expression and ligand-receptor crosstalk

Development ◽  
2019 ◽  
Vol 146 (12) ◽  
pp. dev178673 ◽  
Author(s):  
Alexander N. Combes ◽  
Belinda Phipson ◽  
Kynan T. Lawlor ◽  
Aude Dorison ◽  
Ralph Patrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Marker Gene ◽  
Mouse Kidney ◽  
Cell Analysis ◽  
Marker Gene Expression ◽  
Receptor Crosstalk ◽  
Insight Into

scholarly journals GENE-45. DISSECTING THE DRIVERS OF ADULT H3K27M-GLIOMAS AT THE SINGLE-CELL LEVEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi107-vi107
Author(s):  
Ilon Liu ◽  
Byron Avihai ◽  
Johannes Gojo ◽  
Keith Ligon ◽  
Thomas Czech ◽  
...  
Keyword(s):  
Single Cell ◽  
Time Window ◽  
Molecular Entity ◽  
Single Cell Level ◽  
Cell Level ◽  
Developmental Context ◽  
Level Data ◽  
Cellular Context ◽  
Insight Into ◽  
Shared Gene

Abstract Diffuse midline gliomas are characterized by a lysine27-to-methionine mutation in histone H3 (H3K27M-glioma) and represent a highly aggressive molecular entity of high-grade gliomas. These mutations have primarily been described in children, but are also increasingly recognized in adults. In pediatric H3K27M-gliomas, the transcriptional architecture and cellular composition have been studied at the single-cell level. Data suggest that these tumors arise through malignant transformation of a glial progenitor during a specific neurodevelopmental time window. On the other hand, little is known about the architecture and cellular context of adult H3K27M-gliomas, and it remains to be elucidated whether they are driven by the same or by distinct oncogenic programs as their pediatric counterparts. Here, we utilize single-cell transcriptomics to characterize the transcriptional landscape of five H3K27M-gliomas from adult patients aged 22 to 56 years (median 33 years). We describe the specific cellular and microenvironmental architecture of the adult tumors, which comprises distinct populations of cancer and normal cells. We contrast our findings to 12 location-matched pediatric H3K27M-tumors from patients aged 2.5 to 15 years (median 8 years) to identify features related to tumorigenesis and developmental context in light of the shared hallmark H3K27M mutation. Our preliminary data indicate shared gene expression programs between adult and pediatric tumors. However, we find significant differences in the composition of the immune compartment as well as less pronounced differentiation programs in the adult tumors. Our findings provide an unprecedented insight into the composition of adult H3K27M-gliomas and advance our understanding of this molecular tumor class.

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