Biology subjects

Wells, M. J.

Publications and source records attributed to Wells, M. J..

8 recordsLinked to original sources

bioRxiv2024

Interactive data exploration websites for large-scale electrophysiology

Methodological advances in neuroscience have enabled the collection of massive datasets which demand innovative approaches for scientific communication. Existing platforms for data storage lack intuitive tools for data exploration, limiting our ability to interact effectively with these brain-wide datasets. We introduce two public websites: (Data and Atlas) developed for the International Brain Laboratory which provide access to millions of behavioral trials and hundreds of thousands of individual neurons. These interfaces allow users to discover both the raw and processed brain-wide data released by the IBL at the scale of the whole brain, individual sessions, trials, and neurons. By hosting these data interfaces as websites they are available cross-platform with no installation. By releasing each sites code as a modular open-source framework, other researchers can easily develop their own web interfaces and explore their own data. As neuroscience datasets continue to expand, customizable web interfaces offer a glimpse into a future of streamlined data exploration and act as blueprints for future tools.

neuroscience↗

bioRxiv2023

Incorporation of collagen into Pseudomonas aeruginosa and Staphylococcus aureus biofilms impedes phagocytosis by neutrophils

Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances (EPS) and other components such as proteins. Matrix components can be produced by the microorganisms themselves but can also originate from the environment and then be incorporated into the biofilm. For example, we and our collaborators have recently shown that collagen, a host-produced protein that is abundant in many different infection sites, can be taken up into the matrices of Pseudomonas aeruginosa biofilms, altering biofilm mechanics. In an infection, the biofilm matrix protects bacteria from clearance by the immune system, and some of that protection likely arises from the mechanical properties of the biofilm. P. aeruginosa, Staphylococcus aureus, and Burkholderia pseudomallei are human pathogens notable for forming biofilms in vitro and in vivo in tissues rich in collagen such as lung and skin. Here, we show that the incorporation of Type I collagen into P. aeruginosa, S. aureus, and B. pseudomallei biofilms significantly enhances biofilm elasticity and hinders phagocytosis of biofilm bacteria by human neutrophils. Additionally, enzymatic degradation of collagen using collagenase reverses these effects, increasing biofilm susceptibility to neutrophils. Our findings suggest that host materials play significant roles in stabilizing biofilms and may present promising targets for therapeutic interventions.

microbiology↗

bioRxiv2023

Structure-preserving fixation allows Scanning Electron Microscopy to reveal biofilm microstructure and interactions with immune cells

Pseudomonas aeruginosa is a pathogen that forms robust biofilms which are commonly associated with chronic infections and cannot be successfully cleared by the immune system. Neutrophils, the most common white blood cells, target infections with pathogen-killing mechanisms that are rendered largely ineffective by the protective physicochemical structure of a biofilm. Visualization of the complex interactions between immune cells and biofilms will advance understanding of how biofilms evade the immune system and could aid in developing treatment methods that promote immune clearance with minimal harm to the host. Scanning electron microscopy (SEM) distinguishes itself as a powerful, high-resolution tool for obtaining strikingly clear and detailed topographical images. However, taking full advantage of SEMs potential for high-resolution imaging requires that the fixation process simultaneously preserve both intricate biofilm architecture and the morphologies and structural signatures characterizing neutrophils responses at an infection site. Standard aldehyde-based fixation techniques result in significant loss of biofilm matrix material and morphologies of responding immune cells, thereby obscuring the details of immune interactions with the biofilm matrix. Here we show an improved fixation technique using the cationic dye alcian blue to preserve and visualize neutrophil interactions with the three-dimensional architecture of P. aeruginosa biofilms.

microbiology↗

bioRxiv2023

Physiological concentrations of calcium interact with alginate and extracellular DNA in the matrices of Pseudomonas aeruginosa biofilms to impede phagocytosis by neutrophils

Biofilms are communities of interacting microbes embedded in a matrix of polymer, protein, and other materials. Biofilms develop distinct mechanical characteristics that depend on their predominant matrix components. These matrix components may be produced by microbes themselves or, for infections in vivo, incorporated from the host environment. Pseudomonas aeruginosa is a human pathogen that forms robust biofilms that extensively tolerate antibiotics and effectively evade clearance by the immune system. Two of the important bacterial-produced polymers in the matrices of P. aeruginosa biofilms are alginate and extracellular DNA (eDNA), both of which are anionic and therefore have the potential to interact electrostatically with cations. Many physiological sites of infection contain significant concentrations of the calcium ion (Ca2+). In this study we investigate the structural and mechanical impacts of Ca2+ supplementation in alginate-dominated biofilms grown in vitro and we evaluate the impact of targeted enzyme treatments on clearance by immune cells. We use multiple particle tracking microrheology to evaluate the changes in biofilm viscoelasticity caused by treatment with alginate lyase and/or DNAse I. For biofilms grown without Ca2+, we correlate a decrease in relative elasticity with increased phagocytic success. However, we find that growth with Ca2+ supplementation disrupts this correlation except in the case where both enzymes are applied. This suggests that the calcium cation may be impacting the microstructure of the biofilm in non-trivial ways. Indeed, confocal laser scanning fluorescence microscopy and scanning electron microscopy reveal unique Ca2+-dependent eDNA and alginate microstructures. Our results suggest that the presence of Ca2+ drives the formation of structurally and compositionally discrete microdomains within the biofilm through electrostatic interactions with the anionic matrix components eDNA and alginate. Further, we observe that these structures serve a protective function as the dissolution of both components is required to render biofilm bacteria vulnerable to phagocytosis by neutrophils. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/563605v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@126dc6aorg.highwire.dtl.DTLVardef@50dab8org.highwire.dtl.DTLVardef@477fd6org.highwire.dtl.DTLVardef@19e8e8_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2021

The role of frontal cortex in multisensory decisions

To make accurate perceptual decisions, the brain often combines information across sensory modalities. For instance, localizing objects by integrating their image and sound. However, the cortical substrates underlying this audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. Scanning optogenetic inactivation demonstrated that inactivating frontal cortex impaired choices based on either sensory modality. Recordings from >10,000 neurons indicated that after task learning, activity in frontal area MOs (secondary motor cortex) encodes an additive combination of visual and auditory signals, consistent with the mices behavioral strategy. An accumulator model applied to these sensory representations reproduced both the observed choices and reaction times. These results indicate that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator.

neuroscience↗

bioRxiv2019

RIGBOX: AN OPEN-SOURCE TOOLBOX FOR PROBING NEURONS AND BEHAVIOR

Setting up an experiment in behavioral neuroscience is a complex process that is often managed with ad hoc solutions. To streamline this process we developed Rigbox, a high-performance, open-source software toolbox that facilitates a modular approach to designing experiments (github.com/cortex-lab/Rigbox). Rigbox simplifies hardware I/O, synchronizes data streams from multiple sources, communicates with remote databases, and implements visual and auditory stimuli presentation. Its main submodule, Signals, allows intuitive programming of behavioral tasks. Here we illustrate its function with two interactive examples: a human psychophysics experiment, and the game of Pong. We give an overview of the other packages in Rigbox, provide benchmarks, and conclude with a discussion on the extensibility of the software and comparisons with similar toolboxes. Rigbox runs in MATLAB, with Java components to handle network communication, and a C library to boost performance.

neuroscience↗

bioRxiv2019

Modulation of visual cortex by hippocampal signals

Neurons in primary visual cortex (V1) are influenced by the animals position in the environment and encode positions that correlate with those encoded by hippocampus (CA1). Might V1s encoding of spatial positions be inherited from hippocampal regions? If so, it should depend on non-visual factors that affect the encoding of position in hippocampus, such as the physical distance traveled and the phase of theta oscillations. We recorded V1 and CA1 neurons while mice ran through a virtual corridor and confirmed these predictions. Spatial representations in V1 and CA1 were correlated even in the absence of visual cues. Moreover, similar to CA1 place cells, the spatial responses of V1 neurons were influenced by the physical distance traveled and the phase of hippocampal theta oscillations. These results reveal a modulation of cortical sensory processing by non-sensory estimates of position that might originate in hippocampal regions.

neuroscience↗

bioRxiv2018

Dopaminergic and frontal signals for decisions guided by sensory evidence and reward value

Making efficient decisions requires combining present sensory evidence with previous reward values, and learning from the resulting outcome. To establish the underlying neural processes, we trained mice in a task that probed such decisions. Mouse choices conformed to a reinforcement learning model that estimates predicted value (reward value times sensory confidence) and prediction error (outcome minus predicted value). Predicted value was encoded in the pre-outcome activity of prelimbic frontal neurons and midbrain dopamine neurons. Prediction error was encoded in the post-outcome activity of dopamine neurons, which reflected not only reward value but also sensory confidence. Manipulations of these signals spared ongoing choices but profoundly affected subsequent learning. Learning depended on the pre-outcome activity of prelimbic neurons, but not dopamine neurons. Learning also depended on the post-outcome activity of dopamine neurons, but not prelimbic neurons. These results reveal the distinct roles of frontal and dopamine neurons in learning under uncertainty.

neuroscience↗