Single-cell resolution

Savina Cammalleri discusses extending DISCO, a digital microfluidic platform for single-cell omics, to protein analysis. The work uses controlled handling of individual cells and samples to make proteomic measurements more efficient and scalable. The presentation considers how a flexible microfluidic approach can support studies of variation between cells and the molecular processes underlying that variation. Its goal is to broaden the experimental tools available for biological measurements at single-cell resolution. Cammalleri is a doctoral researcher in biomedical engineering at the Univer

The onset of a stimulus, whether sensory or non-sensory, quenches trial-to-trial neural variability. The universality of this phenomenon across brain areas and species implies that it is a fundamental strategy employed by the brain to boost the fidelity of stimulus representation. Multiple network models have attempted to explain this phenomenon via circuit interactions, but a recent alternative theory proposes a much simpler cell-intrinsic mechanism: stimulus onset increases membrane conductance which itself is enough to quench output variability. Although this model can explain all of the ph

Recent technological advances allow us to measure large populations of neurons across multiple brain regions with millisecond precision and over extended periods while monitoring behavior. These data reveal that both behavior and neural dynamics change over minutes and hours, leading to different behavioral states at the level of single trials. However, many of the current methods and models for linking neural activity and behavior rely on trial-averaged data and often focus on one brain region, limiting our ability to causally link multiregional interactions to flexible behaviors that span sh

…assays to record neural activity at single-cell resolution from the dorsal and lateral cortex of freely running mice during behavior. We found that whole-brain single-cell dyna

A fundamental problem in neuroscience is how neuronal activity in the brain generates organized and stable behaviors across multiple timescales. Recent research in many model organisms, e.g. in monkeys, led to the observations that the neuronal encoding of individual actions, such as preparation for and execution of arm movements, is achieved by large neuronal populations but often lies on low-dimensional manifolds. However, it is largely unclear if such manifolds also coordinate higher dimensional activity patterns that correspond to simultaneously executed fine-tuned movements. In order to a

…we established a whole brain single-cell resolution record

…method which achieves simultaneous single-cell resolution imaging of two cortical planes at a maximum axial separation of 800 μm. This constitutes the larg

Understanding brain activity requires large-scale electrophysiology recording with a single-cell resolution. Over the past decades, the number of electrodes allowed for simultaneous recording doubled approximately every 7 years. Large data from high-density electrodes stress every part of the recording system, including data transmission, storage, and processing, and demands high power. Developing an energy-efficient method to compress the data with minimal distortion is necessary.Spikes are the sparse information carrier in the neural network. The proposed method, focused on spikes, consists

…that link distant brain regions at the single-cell resolution. This approach is enabled by MAPseq, a novel experimental methodology which labels cellular projections with viral barcodes. This recontextualizes single-neuron tracing as a problem of sequencing, overcoming the throughput limitations of prior optical techniques and capitalizing on the swift advancement of modern sequencing technology.Current MAPseq-based long range projection motif analysis methods rely on the

The cerebral cortex is one of the brain structures with the highest cell type diversity. Yet the mechanisms underlying this diversity remain elusive. While various parameters such as gene expression and chromatin accessibility can be assessed within these cells, a dimension of variability that has been largely overlooked is isoform diversity. Pax6 is a fundamental transcription factor during development of the nervous system, especially eye and cortical development. It is also a largely studied homeobox gene, but there is limited knowledge about its isoforms and their specific roles. We studie

…of RNA splicing at single cell resolution using synthetic and natural introns. We show that cryptic splice site usage is not that rare than assumed previously, because the results identify consensus

…image neuronal circuits at cellular resolution across the entire adult brain. Thus, any recording is an implicit subsampling of the total activity, be it by local averaging (e.g. mesoscopic calcium imaging, fMRI), local sampling (e.g.multi-photon microscopy), or spatially distributed sparse sampling (e.g. electrode arrays). Understanding the precise relationship between these different sampling strategies has been a major challenge in neuroscience. Importantly, it is unknown how to trade off th

The hippocampus is necessary for the initial encoding and recent storage of memories; under the standard model of systems consolidation, it is thought that the memory trace eventually reorganizes from the hippocampus to a distributed cortical network, with the anterior cingulate cortex playing a central role in remote memory retrieval. However, little is known about the mechanisms responsible for coordinating this process. Additionally, the intermediate memory representations in the brain and the circuits that might gate and select memories for permanent storage remain unknown. To facilitate t

…programs in the rat brain, with single-cell resolution.

…field of view that also maintains single-cell resolution. Application of our system for imaging neuronal activity has been demonstrated on mice, zebrafish and fruit flies. Website: https://github.com/BadenLab/nTCscope