Biology subjects

Cohen, N.

Publications and source records attributed to Cohen, N..

36 records · Page 2Linked to original sources

bioRxiv2021

Spatial expression programs of the intestinal follicle-associated epithelium

The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte anti-microbial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ sub-epithelial telocytes at the FAE top, which are distinct from villus-tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.

cell biology↗

bioRxiv2021

Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation

A conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naive animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animals behavioral state.

neuroscience↗

bioRxiv2020

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial derived cells and cardiomyocytes

Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection, induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung, and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease. Robust activation of IFN or OAS-RNase L is not observed in these cell types, while PKR activation is evident in iAT2 and iCM. In SARS-CoV-2 infected Calu-3 and A549ACE2 lung-derived cell lines, IFN induction remains relatively weak; however activation of OAS-RNase L and PKR is observed. This is in contrast to MERS-CoV, which effectively inhibits IFN signaling as well as OAS-RNase L and PKR pathways, but similar to mutant MERS-CoV lacking innate immune antagonists. Remarkably, both OAS-RNase L and PKR are activated in MAVS knockout A549ACE2 cells, demonstrating that SARS-CoV-2 can induce these host antiviral pathways despite minimal IFN production. Moreover, increased replication and cytopathic effect in RNASEL knockout A549ACE2 cells implicates OAS-RNase L in restricting SARS-CoV-2. Finally, while SARS-CoV-2 fails to antagonize these host defense pathways, which contrasts with other coronaviruses, the IFN signaling response is generally weak. These host-virus interactions may contribute to the unique pathogenesis of SARS-CoV-2. SignificanceSARS-CoV-2 emergence in late 2019 led to the COVID-19 pandemic that has had devastating effects on human health and the economy. Early innate immune responses are essential for protection against virus invasion. While inadequate innate immune responses are associated with severe COVID-19 diseases, understanding of the interaction of SARS-CoV-2 with host antiviral pathways is minimal. We have characterized the innate immune response to SARS-CoV-2 infections in relevant respiratory tract derived cells and cardiomyocytes and found that SARS-CoV-2 activates two antiviral pathways, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR), while inducing minimal levels of interferon. This in contrast to MERS-CoV which inhibits all three pathways. Activation of these pathways may contribute to the distinctive pathogenesis of SARS-CoV-2.

microbiology↗

bioRxiv2020

Structural and Functional Brain-wide Alterations in A350V IQSEC2 Mutant Mice Displaying Autistic-like Behavior

IQSEC2 is an X-linked gene which is associated with autism spectrum disorder (ASD), intellectual disability and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cortex and hippocampus. Moreover, using a data-driven approach we demonstrate that A350V mice present alterations in structure-function relations of the frontal, auditory, and visual networks. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations. Significance StatementSeveral recent studies have characterized the changes in the organization of brain networks in animal models of autism spectrum disorders (ASD). Here we assessed the effect of an A350V missense mutation in the IQSEC2 gene, which is associated with ASD, on brain-wide functional connectivity and its relation to social behavior deficits in A350V mice relative to controls. We found that the A350V IQSEC2 model results in disrupted functional connectivity of the anterior cingulate cortex and the dorsomedial striatum. Critically, disrupted increased corticostriatal functional connectivity is predictive of individual variability in social interaction only in A350V mice implicating this pathway in the pathophysiology of the A350V IQSEC2 mutation.

neuroscience↗

bioRxiv2020

Inhibition underlies fast undulatory locomotion in C. elegans

Inhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contraction of antagonist muscles, whether along the body axis or within and among limbs. In the nematode C. elegans, a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be necessary for backward undulation because mutants that are defective in GABA transmission exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited by wild-type as well as mutant animals in response to harsh touch to the head or tail, but only GABA transmission mutants show slow locomotion after stimulation. Impairment of GABA transmission, either genetically or optogenetically, induces lower undulation frequency and lower translocation speed during crawling and swimming in both directions. The activity patterns of GABAergic motoneurons are different during low and high undulation frequencies. During low undulation frequency, GABAergic VD and DD motoneurons show similar activity patterns, while during high undulation frequency, their activity alternates. The experimental results suggest at least three non-mutually exclusive roles for inhibition that could underlie fast undulatory locomotion in C. elegans, which we tested with computational models: cross-inhibition or disinhibition of body-wall muscles, or inhibitory reset. Significance StatementInhibition serves multiple roles in the generation, maintenance, and modulation of the locomotive program and supports the alternating activation of antagonistic muscles. When the locomotor frequency increases, more inhibition is required. To better understand the role of inhibition in locomotion, we used C. elegans as an animal model, and challenged a prevalent hypothesis that cross-inhibition supports the dorsoventral alternation. We find that inhibition is related to the speed rather than the direction of locomotion and demonstrate that inhibition is unnecessary for muscle alternation during slow undulation in either direction but crucial to sustain rapid dorsoventral alternation. We combined calcium imaging of motoneurons and muscle with computational models to test hypotheses for the role of inhibition in locomotion.

neuroscience↗

bioRxiv2020

Beyond the connectome: A map of a brain architecture derived from whole-brain volumetric reconstructions

Animal nervous system organization is crucial for all body functions and its disruption can manifest in severe cognitive and behavioral impairment. This organization relies on features across scales, from nano-level localization of synapses, through multiplicities of neuronal morphologies and their contribution to circuit organization, to the high level stereotyped connections between different regions of the brain. The sheer complexity of this organ means that to date, we have yet to reconstruct and model the structure of a complete nervous system that is integrated across all these scales. Here, we present a complete structure-function model of the nematode C. elegans main neuropil, the nerve ring, which we derive by integrating the volumetric reconstruction from two animals with corresponding synaptic and gap junctional connectomes. Whereas previously the nerve ring was considered a densely packed tract of axons, we uncover internal organization into 5 functional bundles and show how they spatially constrain and support the synaptic connectome. We find that the C. elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and propose a corresponding reference connectome for the core circuit. Using this reference, we show that the architecture of the C. elegans brain can be viewed as a modular Residual Network that supports sensory computation and integration, sensory-motor convergence, and brain-wide coordination. These findings point to scalable and robust features of brain organization that are likely universal across phyla.

neuroscience↗

bioRxiv2020

Brain-wide structural and functional disruption in mice with oligodendrocyte specific Nf1 deletion is rescued by inhibition of NOS

Neurofibromin gene (NF1) mutation causes Neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice, Nf1 loss in adult oligodendrocyte causes myelin decompaction, and increases oligodendrocyte nitric oxide (NO) levels. Nitric oxide synthase (NOS) inhibitors rescue this pathology. Whether oligodendrocyte pathology is sufficient to affect brainwide structure and account for NF1 imaging findings is unknown. Here, we show that Nf1 gene inactivation in adult oligodendrocytes (Plp-Nf1fl/+ mice) results in a motor coordination deficit. Magnetic resonance imaging in awake mice shows that fractional anisotropy is reduced in Plp-Nf1fl/+ corpus callosum and that interhemispheric functional connectivity in motor cortex is also reduced, consistent with disrupted myelin integrity. Further, NOS-specific inhibition rescued both measures. These results demonstrate that oligodendrocyte defects account for aspects of brain dysfunction in NF1, which can be identified by neuroimaging and ameliorated by NOS inhibition. Significance statementThis study assesses the effects of myelin decompaction on motor behavior and brain-wide structural and functional connectivity, and the effect of nitric oxide synthase (NOS) inhibition by N-nitro-L-arginine methyl ester (L-NAME) on these imaging measures. We report that inducible oligodendrocyte-specific inactivation of the Nf1 gene, which causes myelin decompaction, results in reduced motor coordination. Using diffusion-based MRI we show reduced myelin integrity and using functional MRI we show reduced functional connectivity in awake passive mice. L-NAME administration results in rescue of the pathology at the mesoscopic level using imaging procedures that can be directly applied to humans to study treatment efficacy in clinical trials.

neuroscience↗

bioRxiv2020

Spatio-temporal Proteomic Analysis of Stress Granule disassembly using APEX Reveals Regulation by SUMOylation and links to ALS pathogenesis

Cytoplasmic stress granules (SG) form in response to a variety of cellular stresses by phase-separation of proteins associated with non-translating mRNAs. SG provide insight into the biology of neurodegeneration, including amyotrophic lateral sclerosis (ALS) because they approximate some of the molecular conditions for nucleation of insoluble aggregates in neuropathological inclusions. Whereas much has been learned about SG formation, a major gap remains in understanding the compositional changes SG undergo during normal disassembly and under disease conditions. Here, we address this gap by proteomic dissection of SG temporal disassembly sequence, using multi-bait APEX proximity-proteomics. We discover 109 novel SG-proteins and characterize at proteomic resolution two biophysically distinct SG substructures. We further demonstrate that dozens of additional proteins are recruited to SG specifically during disassembly, indicating that it is a highly regulated process. The involved proteins link SG disassembly, to mitochondrial biology and the cytoskeleton. Parallel analysis with C9ORF72-associated dipeptides, which are found in patients with ALS and frontotemporal dementia, demonstrated compositional changes in SG during the course of disassembly and focused our attention on the roles SUMOylation in SG disassembly. We demonstrate that broad SUMOylation of SG-proteins is required for SG disassembly and is impaired by C9ORF72-associated dipeptides, representing an unexplored potential molecular mechanism of neurodegeneration. Altogether, out study fundamentally increases the knowledge about SG composition in human cells by dissecting the SG spatio-temporal proteomic landscape, provides an in-depth resource for future work on SG function and reveals basic and disease-relevant mechanisms of SG disassembly. HighlightsO_LIMulti bait APEX proximity labelling reveals 109 novel SG proteins and two distinct SG substructures. C_LIO_LIProteomic dissection of SG temporal disassembly under basal conditions and with a model of neurodegeneration. C_LIO_LIDisassembly-engaged proteins (DEPs) include SUMO ligases that are recruited during normal disassembly and dysregulated in ALS-like conditions. C_LIO_LIPervasive SG protein SUMOylation during SG disassembly is impaired by ALS-like conditions. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/830133v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@15899daorg.highwire.dtl.DTLVardef@1dcd399org.highwire.dtl.DTLVardef@c7ef12org.highwire.dtl.DTLVardef@20c096_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2019

Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity

Mortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with worse survival in human breast cancer.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2019

Changes in anterior and posterior hippocampus differentially predict item-space, item-time, and item-item memory improvement

Relational memory requires the hippocampus, but whether distinct hippocampal mechanisms along the anterior-posterior axis are required for different types of relations is debated. We investigated the contribution of structural changes in hippocampal head, body, and tail subregions to the capacity to remember item-space, item-time, and item-item relations. Memory for each relation and volumes of hippocampal subregions were assessed longitudinally in 171 participants across 3 time points (Mage at T1= 9.45 years; Mage at T2= 10.86 years, Mage at T3=12.12 years; comprising 393 behavioral assessments and 362 structural scans). Among older children, volumetric growth in: (a) head and body predicted improvements in item-time memory, (b) head predicted improvements in item-item memory; and (c) right tail predicted improvements in item-space memory. The present research establishes that volumetric changes in hippocampal subregions differentially predict changes in different aspects of relational memory, underscoring a division of labor along the hippocampal anterior-posterior axis.

neuroscience↗

bioRxiv2019

Multiplexed electron microscopy by fluorescent barcoding allows screening for ultrastructural phenotype

Genetic screens performed using high-throughput fluorescent microscopes have generated large datasets that have contributed many insights into cell biology. However, such approaches typically cannot tackle questions requiring knowledge of ultrastructure below the resolution limit of fluorescent microscopy. Electron microscopy (EM) is not subject to this resolution limit, generating detailed images of cellular ultrastructure, but requires time consuming preparation of individual samples, limiting its throughput. Here we overcome this obstacle and describe a robust method for screening by high-throughput electron microscopy. Our approach uses combinations of fluorophores as barcodes to mark the genotype of each cell in mixed populations, and correlative light and electron microscopy to read the fluorescent barcode of each cell before it is imaged by electron microscopy. Coupled with an easy-to-use software workflow for correlation, segmentation and computer image analysis, our method allows to extract and analyze multiple cell populations from each EM sample preparation. We demonstrate the method on several organelles with samples that each contain up to 15 different yeast variants. The methodology is not restricted to yeast, can be scaled to higher-throughput, and can be utilized in multiple ways to enable electron microscopy to become a powerful screening methodology.

cell biology↗

bioRxiv2018

Volumetric reconstruction of main Caenorhabditis elegans neuropil at two different time points

Detailed knowledge of both synaptic connectivity and the spatial proximity of neurons is crucial for understanding wiring specificity in the nervous system. Here, we volumetrically reconstructed the C. elegans nerve ring from legacy serial-sectioned electron micrographs at two distinct time points: the L4 and young adult. The new volumetric reconstructions provide detailed spatial and morphological information of neural processes in the nerve ring. Our analysis suggests that the nerve ring exhibits three levels of wiring specificity: spatial, synaptic and subcellular. Neuron classes innervate well defined neighborhoods and aggregate functionally similar synapses to support distinct computational pathways. Connectivity fractions vary based on neuron class and synapse type. We find that the variability in process placement accounts for less than 20% of the variability in synaptic connectivity and models based only on spatial information cannot account for the reproducibility of synaptic connections among homologous neurons. This suggests that additional, non-spatial factors also contribute to synaptic and subcellular specificity. With this in mind, we conjecture that a spatially constrained, genetic model could provide sufficient synaptic specificity. Using a model of cell-specific combinatorial genetic expression, we show that additional specificity, such as sub-cellular domains or alternative splicing, would be required to reproduce the wiring specificity in the nerve ring.

developmental biology↗

bioRxiv2018

LINGO3 interacts with Trefoil factor 2 to enforce mucosal barrier integrity and drive tissue repair during colitis

Mucosal epithelia are constantly exposed to damaging stimuli from mechanical, chemical, or biologic entities, and depend on rapid repair mechanisms to maintain tissue homeostasis and immunological quiescence. The reparative cytokine Trefoil factor 2 (TFF2) serves to enforce mucosal barrier integrity, but whether TFF2 receptor(s) exist is controversial. Herein, we demonstrate leucine rich repeat and immunoglobulin like domain containing nogo receptor interacting protein 3 (LINGO3) is a necessary transmembrane component for TFF2-mediated ERK signaling, proliferation, and recovery of trans-epithelial resistance of primary epithelia during wound healing. Human respiratory and intestinal epithelia express LINGO3 and mice lacking Lingo3 have impaired intestinal barrier function and fail to recover from DSS-induced colitis. Compared to wild-type controls, LINGO3 deficiency impairs both crypt regeneration and expression of the intestinal stem cell marker Lgr5. Importantly, Lingo3-/- mice display a phenotype similar to that previously reported for Tff2 deficiency, with increased paracellular permeability, and significant accumulation of mucosal CD4+ TH1 cells expressing IFN{gamma}+ TNF+ even under steady-state conditions. Combined, these data reveal a previously unrecognized role for LINGO3 as a putative TFF2 receptor that regulates mucosal barrier integrity and GI inflammation.\n\nSignificanceIntestinal epithelial cells (IEC) are necessary for maintenance of homeostasis, resistance to infectious organisms, and overall organismal health. When injured the IEC and the underlying stroma and progenitor cell pool undergo restitutive and regenerative processes driven by the reparative cytokine Trefoil factor 2 (TFF2). This report identifies a novel receptor component for TFF2 signaling expressed on both human and mouse epithelial cells that is necessary for barrier integrity at the steady state and during colitic disease. The discovery of a novel TFF2-LINGO3 axis sheds new light on the processes controlling tissue repair, restitution, and regeneration at the mucosal interface.

cell biology↗

bioRxiv2018

Intrinsic and Extrinsic Modulation of C. elegans Locomotion

Animal locomotion describes the coordinated self-propelled movement of a body, subject to the combined effects of internal muscle forcing and external forces. Here we use an integrated neuromechanical computational model to study the combined effects of neural modulation, mechanical modulation and modulation of the external environments on undulatory forward locomotion in the nematode C. elegans. In particular we use a proprioceptively driven neural control circuit to consider the effects of proprioception, body elasticity and environmental drag on the waveform, frequency and speed of undulations. We find qualitative differences in the frequency-wavelength relationship obtained under extrinsic modulation of the environmental fluid or body elasticity versus intrinsic modulation due to changes in the sensorimotor control. We consider possible targets of modulation by the worm and implications of our results for our understanding of the neural control of locomotion in this system.

neuroscience↗

bioRxiv2018

Neuromechanical phase lag predicts material and neural control properties in Caenorhabditis elegans

In all animals, the successful orchestration of motor programs hinges on appropriate coupling between components of the system, from neural circuit dynamics, through muscles and body properties to the physical environment. We study this coupling in undulatory locomotion, with a view to better understanding the relative roles of central and reflex-driven control. We ask how the coupling between neural control and body mechanics is affected by sensory inputs during undulatory locomotion in C. elegans. To address this question, we use a biomechanical simulation framework, within which we separately model feed forward and feedback controlled undulations. We characterize neuromechanical phase lag and locomotion speed using body stiffness as a control parameter. We show that sensory entrainment can suppress neuromechanical phase lag, that would otherwise emerge under centrally generated feed forward control.

neuroscience↗

bioRxiv2018

Spacing of Cue-approach Training Leads to Better Maintenance of Behavioral Change

The maintenance of behavioral change over the long term is essential to achieve public health goals such as combatting obesity and drug use. Previous work by our group has demonstrated a reliable shift in preferences for appetitive foods following a novel non-reinforced training paradigm. In the current studies, we tested whether distributing training trials over two consecutive days would affect preferences immediately after training as well as over time at a one-month follow-up. In four studies, three different designs and an additional pre-registered replication of one sample, we found that spacing of cue-approach training induced a shift in food choice preferences over one month. The spacing and massing schedule employed governed the long-term changes in choice behavior. Applying spacing strategies to training paradigms that target automatic processes could prove a useful tool for the long-term maintenance of health improvement goals with the development of real-world behavioral change paradigms that incorporate distributed practice principles.

animal behavior and cognition↗

bioRxiv2017

Prestimulus Activity in the Cingulo-Opercular Network Predicts Memory for Naturalistic Episodic Experience

Human memory is strongly influenced by brain states occurring before an event, yet we know little about the underlying mechanisms. We found that activity in the cingulo-opercular network (including bilateral anterior insula and anterior prefrontal cortex) seconds before an event begins can predict whether this event will subsequently be remembered. We then tested how activity in the cingulo-opercular network shapes memory performance. Our findings indicate that prestimulus cingulo-opercular activity affects memory performance by opposingly modulating subsequent activity in two sets of regions previously linked to encoding and retrieval of episodic information. Specifically, higher prestimulus cingulo-opercular activity was associated with a subsequent increase in activity in temporal regions previously linked to encoding and with a subsequent reduction in activity within a set of regions thought to play a role in retrieval and self-referential processing. Together, these findings suggest that prestimulus attentional states modulate memory for real-life events by enhancing encoding and possibly by dampening interference from competing memory substrates.

neuroscience↗

bioRxiv2017

Identification Of Cellular-Activity Dynamics Across Large Tissue Volumes In The Mammalian Brain

Tracking the coordinated activity of cellular events through volumes of intact tissue is a major challenge in biology that has inspired significant technological innovation. Yet scanless measurement of the high-speed activity of individual neurons across three dimensions in scattering mammalian tissue remains an open problem. Here we develop and validate a computational imaging approach (SWIFT) that integrates high-dimensional, structured statistics with light field microscopy to allow the synchronous acquisition of single-neuron resolution activity throughout intact tissue volumes as fast as a camera can capture images (currently up to 100 Hz at full camera resolution), attaining rates needed to keep pace with emerging fast calcium and voltage sensors. We demonstrate that this large field-of-view, single-snapshot volume acquisition method--which requires only a simple and inexpensive modification to a standard fluorescence microscope--enables scanless capture of coordinated activity patterns throughout mammalian neural volumes. Further, the volumetric nature of SWIFT also allows fast in vivo imaging, motion correction, and cell identification throughout curved subcortical structures like the dorsal hippocampus, where cellular-resolution dynamics spanning hippocampal subfields can be simultaneously observed during a virtual context learning task in a behaving animal. SWIFTs ability to rapidly and easily record from volumes of many cells across layers opens the door to widespread identification of dynamical motifs and timing dependencies among coordinated cell assemblies during adaptive, modulated, or maladaptive physiological processes in neural systems.

neuroscience↗