bioRxiv Subject Collection: Neuroscience's Journal
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Tuesday, October 15th, 2024
| Time |
Event |
| 2:46a |
High-throughput two-photon volumetric brain imaging in freely moving mice
Imaging neural activities across large volumes at subcellular resolution without impeding animal behaviors remains difficult. Here we introduce a high-throughput miniature Bessel-beam two-photon microscope capable of imaging calcium dynamics from neurons and dendrites over a volume of 420 x 420 x 80 m3 during free behavior. We share full description of the microscope and demonstrate calcium imaging of more than 1000 neurons at a time in freely moving mice. | | 2:46a |
Inhibition Resolves Simon Conflict: Evidence from EEG Decoding
The congruency sequence effect (CSE), a hypothesized marker of top-down cognitive control, refers to a reduced congruency effect after incongruent trials compared to congruent trials. Although this effect has been observed across various distractor interference tasks, the nature of the control processes underlying the CSE remains a topic of active debate. It has been suggested that cognitive control may resolve conflicts in information processing either by (a) enhancing the representation of goal information and/or (b) suppressing the representation of distractor information. The present study aimed to identify the conflict resolution processes within the context of the color Simon task by decoding the goal and distracting information from human scalp EEG signals. For the decoding analysis, models were trained separately for color and location attributes corresponding to goal and distractor information. Additionally, decoding accuracy was calculated in different frequency bands: theta (4-8 Hz), alpha (8-12 Hz), low beta (12-20 Hz), and high beta (20-30 Hz). Results showed that decoding accuracy for distractor information was reduced when cognitive control was activated and this pattern was only observed in the high beta-frequency band (20-30 Hz). In contrast, no such difference was observed for target information. These findings suggest that cognitive control regulates Simon conflict by inhibiting distractor representation in the brain, thereby preventing unwanted distraction-driven behaviors. | | 2:46a |
Assembloid model to study loop circuits of the human nervous system
Neural circuits connecting the cerebral cortex, the basal ganglia and the thalamus are fundamental networks for sensorimotor processing and their dysfunction has been consistently implicated in neuropsychiatric disorders. These recursive, loop circuits have been investigated in animal models and by clinical neuroimaging, however, direct functional access to developing human neurons forming these networks has been limited. Here, we use human pluripotent stem cells to reconstruct an in vitro cortico-striatal-thalamic-cortical circuit by creating a four-part loop assembloid. More specifically, we generate regionalized neural organoids that resemble the key elements of the cortico-striatal-thalamic-cortical circuit, and functionally integrate them into loop assembloids using custom 3D-printed biocompatible wells. Volumetric and mesoscale calcium imaging, as well as extracellular recordings from individual parts of these assembloids reveal the emergence of synchronized patterns of neuronal activity. In addition, a multi-step rabies retrograde tracing approach demonstrate the formation of neuronal connectivity across the network in loop assembloids. Lastly, we apply this system to study heterozygous loss of ASH1L gene associated with autism spectrum disorder and Tourette syndrome and discover aberrant synchronized activity in disease model assembloids. Taken together, this human multi-cellular platform will facilitate functional investigations of the cortico-striatal-thalamic-cortical circuit in the context of early human development and in disease conditions. | | 3:15a |
Cataract induction in an arthropod reveals how lens crystallins contribute to the formation of biological glass
Lenses are vital components of eyes, crafted through the precise arrangement of proteins to achieve transparency and focusing power, and placed appropriately within the eye for the retina to receive sharp, focused images. Maintaining these states is challenging due to substantial post-embryonic eye and lens growth. Here, we gain insights into required processes by exploring consequences of silencing Lens3, a key lens protein, during growth in Thermonectus marmoratus sunburst diving beetle larvae. We show that lens3RNAi leads to opaque aggregates reminiscent of vertebrate lens cataracts, causing the projection of degraded images which impact behaviour in low light. Our findings uncover how complex biological lenses are constructed and further support that visual input is inconsequential for coordinated eye growth in this clade. We highlight the utility of this insect as a tractable model system to investigate the aetiology of lens cataracts and refractive errors in a sophisticated camera-type eye. | | 3:50a |
Tau load in select brainstem neurons predicts the severity and nature of balance deficits in the absence of cell death
Patients with tauopathies present with profoundly different clinical symptoms, even within the same disorder. A central hypothesis in the field, well-supported by biomarker studies and post-mortem pathology, is that clinical heterogeneity reflects differential degeneration of vulnerable neuronal populations responsible for specific neurological functions. Recent work has revealed mechanisms underlying susceptibility of particular cell types, but relating tau load to disrupted behavior -- especially before cell death -- requires a targeted circuit-level approach. Here we studied two distinct balance behaviors in larval zebrafish expressing a human 0N/4R-tau allele in select populations of evolutionarily-conserved and well-characterized brainstem vestibular circuits. We observed that human tau load predicted the severity of circuit-specific deficits in posture and navigation in the absence of cell death. Targeting expression to either mid- or hindbrain balance neurons recapitulated particular deficits in posture and navigation. By parametrically linking tau load in specific neurons to early behavioral deficits, our work moves beyond cell type to close the gap between pathological and neurological conceptions of tauopathy. | | 4:49p |
Privacy-Preserving Visualization of Brain Functional Connectivity
Privacy protection is important in visualization due to the risk of leaking personal sensitive information. In this paper, we study the problem of privacy-preserving visualizations using differential privacy, employing biomedical data from neuroimaging as a use case. We investigate several approaches based on perturbing correlation values and characterize their privacy cost and the impact of pre- and post-processing. To obtain a better privacy/visual utility tradeoff, we propose workflows for connectogram and seed-based connectivity visualizations, respectively. These workflows successfully generate visualizations similar to their non-private counterparts. Experiments show that qualitative assessments can be preserved while guaranteeing privacy. These results show that differential privacy is a promising method for protecting sensitive information in data visualization. | | 11:18p |
Most L1CAM is not associated with extracellular vesicles in human biofluids and iPSC-derived neurons
Transmembrane L1 cell adhesion molecule (L1CAM) is widely used as a marker to enrich for neuron-derived extracellular vesicles (EVs), especially in plasma. However, this approach lacks sufficient robust validation. This study aimed to assess whether human biofluids are indeed enriched for EVs, particularly neuron-derived EVs, by L1CAM immunoaffinity, utilizing multiple sources (plasma, CSF, conditioned media from iPSC-derived neurons [iNCM]) and different methods (mass spectrometry [MS], nanoparticle tracking analysis [NTA]). Following a systematic multi-step validation approach, we confirmed isolation of generic EV populations using size-exclusion chromatography (SEC) and polymer-aided precipitation (PPT) - two most commonly applied EV isolation methods - from all sources. Neurofilament light (NfL) was detected in both CSF and blood-derived EVs, indicating their neuronal origin. However, L1CAM immunoprecipitation did not yield enrichment of L1CAM in EV fractions. Instead, it was predominantly found in its free-floating form. Additionally, MS-based proteomic analysis of CSF-derived EVs also did not show L1CAM enrichment. Our study validates EV isolation from diverse biofluid sources by several isolation approaches and confirms that some EV subpopulations in human biofluids are of neuronal origin. Thorough testing across multiple sources by different orthogonal methods, however, does not support L1CAM as a marker to reliably enrich for a specific subpopulation of EVs, particularly of neuronal origin. | | 11:18p |
Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells
Loss of retinal pigment epithelium (RPE) cells in the eye leads to photoreceptor death and vision loss. Cell replacement strategies using RPE derived in vitro from pluripotent stem cells (PSCs) has emerged as a promising therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM- was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation. |
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