Biology subjects

Bennett, C.

Publications and source records attributed to Bennett, C..

26 records · Page 2Linked to original sources

bioRxiv2021

Backward masking in mice requires visual cortex

Visual masking is used to infer the timescale of conscious perception in humans; yet the underlying circuit mechanisms are not understood. Here we describe a two-alternative choice backward masking task in mice and humans, in which the location of a briefly presented grating is effectively masked within a 50 ms window after stimulus onset. Importantly, human subjects reported reduced perceptual visibility during masking that closely corresponded with behavior deficits. In mice, optogenetic silencing of visual cortex reduces performance over a similar time course as masking. However, response rates and accuracy do not match masking, demonstrating that cortical silencing and masking are distinct phenomena. Spiking responses recorded in primary visual cortex (V1) are consistent with masked behavior when quantified over long, but not short, time windows, indicating masking involves further downstream processing. Behavioral performance can be quantitatively recapitulated by a dual accumulator model constrained by V1 activity. The model and the animals performance for the earliest decisions imply that the initial spike arriving from the periphery can trigger a correct response, but subsequent V1 spikes, evoked by the mask, degrade performance for longer decisions. To test the necessity of visual cortex for backward masking, we optogenetically silenced mask-evoked cortical activity which fully restored discrimination of target location. Together, these results demonstrate that mice, like humans, are susceptible to backward visual masking and that visual cortex has a crucial role in this process.

neuroscience↗

bioRxiv2021

TReNCo: Topologically associating domain (TAD) aware regulatory network construction

There has long been a desire to understand, describe, and model gene regulatory networks controlling numerous biologically meaningful processes like differentiation. Despite many notable improvements to models over the years, many models do not accurately capture subtle biological and chemical characteristics of the cell such as high-order chromatin domains of the chromosomes. Topologically Associated Domains (TAD) are one of these genomic regions that are enriched for contacts within themselves. Here we present TAD-aware Regulatory Network Construction or TReNCo, a memory-lean method utilizing epigenetic marks of enhancer and promoter activity, and gene expression to create context-specific transcription factor-gene regulatory networks. TReNCo utilizes common assays, ChIP-seq, RNA-seq, and TAD boundaries as a hard cutoff, instead of distance based, to efficiently create context-specific TF-gene regulatory networks. We used TReNCo to define the enhancer landscape and identify transcription factors (TFs) that drive the cardiac development of the mouse. Our results show that we are able to build specialized adjacency regulatory network graphs containing biologically relevant connections and time dependent dynamics.

bioinformatics↗

bioRxiv2021

SeqWho: Reliable, rapid determination of sequence file identity using k-mer frequencies

With the vast improvements in sequencing technologies and increased number of protocols, sequencing is finding more applications to answer complex biological problems. Thus, the amount of publicly available sequencing data has tremendously increased in repositories such as SRA, EGA, and ENCODE. With any large online database, there is a critical need to accurately document study metadata, such as the source protocol and organism. In some cases, this metadata may not be systematically verified by the hosting sites and may result in a negative influence on future studies. Here we present SeqWho, a program designed to heuristically assess the quality of sequencing files and reliably classify the organism and protocol type. This is done in an alignment-free algorithm that leverages a Random Forest classifier to learn from native biases in k-mer frequencies and repeat sequence identities between different sequencing technologies and species. Here, we show that our method can accurately and rapidly distinguish between human and mouse, nine different sequencing technologies, and both together, 98.32%, 97.86%, and 96.38% of the time in high confidence calls respectively. This demonstrates that SeqWho is a powerful method for reliably checking the identity of the sequencing files used in any pipeline and illustrates the programs ability to leverage k-mer biases.

bioinformatics↗

bioRxiv2020

HISAT-3N: a rapid and accurate three-nucleotide sequence aligner

Nucleotide conversion sequencing technologies such as bisulfite-seq and SLAM-seq are powerful tools to explore the intricacies of cellular processes. In this paper, we describe HISAT-3N (hierarchical indexing for spliced alignment of transcripts - 3 nucleotides), which rapidly and accurately aligns sequences consisting of nucleotide conversions by leveraging powerful hierarchical index and repeat index algorithms originally developed for the HISAT software. Tests on real and simulated data sets demonstrate that HISAT-3N is over 7 times faster, has greater alignment accuracy, and has smaller memory requirements than other modern systems. Taken together HISAT-3N is the ideal aligner for use with converted sequence technologies.

bioinformatics↗

bioRxiv2020

Dietary folic acid deficiency impacts hippocampal morphology and cortical acetylcholine metabolism in adult male and female mice

ObjectiveOne-carbon metabolism is a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. There are sex differences in hepatic one-carbon metabolism. However, it is unclear whether there are sex differences in dietary deficiencies of one-carbon metabolism in the brain. The aim of this study was to investigate if sex modulates the effects of dietary folic acid deficiency in brain tissue using a mouse model. MethodsMale and female C57Bl/6J mice were placed on a folic acid deficient (FD) or control diet (CD) at six weeks of age. Mice were maintained on these diets for six months, after which animals were euthanized and brain tissue and serum were collected for analysis. Serum folate levels were measured. In brain tissue, hippocampal volume and morphology including Cornu Ammonis 1 and 3 (CA1; CA3), and dentate gyrus thickness were measured. Apoptosis within the hippocampus was assessed using active caspase-3 immunofluorescence staining. Additionally, cortical acetylcholine metabolism was measured in brain tissue using immunofluorescence staining of acetylcholinesterase (AChE), or choline acetyltransferase (ChAT), and neuronal nuclei (NeuN). ResultsMale and female FD mice had reduced serum levels of folate. Both males and females maintained on a FD showed a decrease in the thickness of the hippocampal CA1-CA3 region. Interestingly, there was a sex difference in the levels of active caspase-3 within the CA3 region of the hippocampus. In cortical tissue, there were increased levels of neuronal ChAT and reduced levels of AChE in FD females and male mice. ConclusionsThe results indicated that FD impacts hippocampal morphology and cortical neuronal acetylcholine metabolism. The data from our study indicate that there was only one sex difference and that was in hippocampal apoptosis. Our study provides little evidence that sex modulates the effects of dietary folate deficiency on hippocampal morphology and cortical neuronal acetylcholine metabolism.

neuroscience↗

bioRxiv2019

A survey of spiking activity reveals a functional hierarchy of mouse corticothalamic visual areas

The mammalian visual system, from retina to neocortex, has been extensively studied at both anatomical and functional levels. Anatomy indicates the cortico-thalamic system is hierarchical, but characterization of cellular-level functional interactions across multiple levels of this hierarchy is lacking, partially due to the challenge of simultaneously recording activity across numerous regions. Here, we describe a large, open dataset (part of the Allen Brain Observatory) that surveys spiking from units in six cortical and two thalamic regions responding to a battery of visual stimuli. Using spike cross-correlation analysis, we find that inter-area functional connectivity mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. Classical functional measures of hierarchy, including visual response latency, receptive field size, phase-locking to a drifting grating stimulus, and autocorrelation timescale are all correlated with the anatomical hierarchy. Moreover, recordings during a visual task support the behavioral relevance of hierarchical processing. Overall, this dataset and the hierarchy we describe provide a foundation for understanding coding and dynamics in the mouse cortico-thalamic visual system.

neuroscience↗

bioRxiv2018

Distinct higher-order thalamic circuits channel parallel streams of visual information in mice

Higher-order thalamic nuclei, such as the visual pulvinar, play essential roles in cortical function by connecting functionally-related cortical and subcortical brain regions. Yet a coherent framework describing pulvinar function remains elusive due to its anatomical complexity and involvement in diverse cognitive processes. Here we combined large-scale anatomical circuit mapping with high-density electrophysiological recordings to dissect a homolog of pulvinar in mice, the lateral posterior nucleus (LP). We define three broad LP subregions based on correspondence between input/output connectivity and functional properties. These subregions form corticothalamic loops biased towards ventral or dorsal stream cortical areas and contain separate representations of visual space. To reveal which input sources drive LP activity, we silenced visual cortex or superior colliculus and found they drive visual tuning properties in separate LP subregions. Thus, by specifying the driving input sources, functional properties, and downstream targets of LP circuits, our data provide a roadmap for understanding the mechanisms of higher-order thalamic function in vision.

neuroscience↗

bioRxiv2018

High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification

Different neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morpho-electric properties of neurons measured on spatially dense electrode arrays might be useful for distinguishing neuron types. Here we used Neuropixels probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multi-channel compared to single-channel waveforms. In visual cortex, waveform clustering identified the canonical regular spiking (RS) and fast spiking (FS) classes, but also uncovered a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spikes from high-density probes aids neuron identification and can reveal dendritic backpropagation.

neuroscience↗