Biology subjects

Brosch, M.

Publications and source records attributed to Brosch, M..

8 recordsLinked to original sources

bioRxiv2026

Miniscope Zero: a fully wireless, single-cell-resolution miniature microscope for imaging neural dynamics in freely behaving animals

Imaging neural fluorescence dynamics during unconstrained behavior remains a major challenge in neuroscience. Head-mounted miniature one-photon microscopes enable in vivo recordings from freely behaving animals. Still, their power and data requirements typically necessitate tethers or heavy batteries, which constrain experiments and may introduce behavioral artifacts. We present Miniscope Zero, a fully wireless miniature microscope platform combining quasistatic cavity resonance (QSCR) wireless power transfer with a high-bandwidth optical data link. The system delivers >500 mW of receiver power across a 2,500 cm2 behavioral arena and streams imaging data at 8 Mbps, supporting real-time data acquisition. Miniscope Zero provides a typical field of view of 600 m x 600 m and a 2.6-fold higher light-collection efficiency than the UCLA Miniscope v4. We demonstrate wireless CA1 GCaMP6f recordings during open-field navigation, enclosed-maze exploration, simultaneous multi-animal imaging, and extended three-dimensional behavior, enabling long-duration cellular-resolution imaging without tether-induced constraints.

neuroscience↗

bioRxiv2026

Safety of Subdural Direct Current Stimulation: A Histological Study in the Ovine Brain

BackgroundDirect current (DC) stimulation can modulate neuronal activity in ways that differ from pulsatile stimulation, but its intracranial use has been limited by concerns about tissue injury at the electrode/tissue interface. Quantitative safety limits for DC delivered through metal electrodes directly to the brain remain poorly defined. ObjectiveTo estimate histological safety boundaries for DC stimulation delivered through metal electrodes in a large-brain gyrencephalic animal model. MethodsCathodal DC stimulation was applied to the exposed cortical surface of ten anesthetized sheep using platinum-iridium disc electrodes typically used in clinical applications (surface area [≤] 4.15 mm2). Currents of 5 to 1000 {micro}A were delivered for 10 to 15 minutes at 36 cortical sites. Stimulation dose was quantified as charge density. Brains were removed shortly after stimulation and examined histologically for tissue damage, including necrosis, inflammation, gliosis, and demyelination. Lesion volumes were quantified and related to charge density. ResultsNo lesions were observed at sites where no current or a low charge density (0.7 mC/mm2) was delivered. With stimulation, lesion probability and volume increased with charge density, although variability was substantial. Lesions occurred in 3 of 18 sites at lower charge densities (1.4 to 10 mC/mm2) and in 5 of 9 sites at higher charge densities (14.4 to 144.4 mC/mm2). Linear regression of lesion volume against charge density yielded an estimated zero-lesion intercept of 2.3 mC/mm2, whereas alternative nonlinear models predicted thresholds up to 8.7 mC/mm2. ConclusionThese findings suggest that it may be possible to apply cathodal DC stimulation directly to the cortical surface through metal electrodes without detectable histological damage when current intensity, duration, and electrode size are appropriately constrained. These findings provide quantitative guidance for the safe application of DC directly to neural tissue in experimental and translational neuromodulation studies.

neuroscience↗

bioRxiv2026

Linking working memory maintenance and readout in monkey sensory and prefrontal cortex

Despite extensive research, the neural implementation of working memory, from information maintenance to readout that guides behavior, remains elusive. We provide direct evidence that neurons in auditory and prefrontal cortices of monkeys maintain tone-specific information via persistent changes in spiking during the memory delay. Crucially, during the subsequent readout phase, these same memory neurons transition to reflect the monkeys behavioral decisions, demonstrating a direct role in translating maintained information into action. The functional necessity of this neuronal implementation is confirmed by causal perturbations that impaired working memory performance. Notably, memory neurons could only be identified by comparing delay periods between tasks with different memory demands, rather than the typical approach of contrasting delay and baseline periods within a single task. These findings challenge previous efforts to localize working memory neurons and necessitate a fundamental reassessment of working memory mechanisms, reshaping both conceptual and methodological frameworks for future research.

neuroscience↗

bioRxiv2024

Hemispheric difference of adaptation lifetime in human auditory cortex measured with MEG

Adaptation is the attenuation of a neuronal response when a stimulus is repeatedly presented. The phenomenon has been linked to sensory memory, but its exact neuronal mechanisms are under debate. One defining feature of adaptation is its lifetime, that is, the timespan over which the attenuating effect of previous stimulation persists. This can be revealed by varying the stimulus-onset interval (SOI) of the repeated stimulus. As SOI is increased, the peak amplitude of the response grows before saturating at large SOIs. The rate of this growth can be quantified and used as an estimate of adaptation lifetime. Here, we studied whether adaptation lifetime varies across the left and the right auditory cortex of the human brain. Event-related fields of whole-head magnetoencephalograms (MEG) were measured in 14 subjects during binaural presentation of pure tone stimuli. To make statistical inferences on the single-subject level, additional event-related fields were generated by resampling the original single-trial data via bootstrapping. For each hemisphere and SOI, the peak amplitude of the N1m response was then derived from both original and bootstrap-based data sets. Finally, the N1m peak amplitudes we used for deriving subject-and hemisphere-specific estimates of adaptation lifetime. Comparing subject-specific adaptation lifetime across hemispheres, we found a significant difference, with longer adaptation lifetimes in the left than in the right auditory cortex (p = 0.004). This difference might have a functional relevance in the context of temporal binding of auditory stimuli, leading to larger integration time windows in the left than in the right hemisphere.

neuroscience↗

bioRxiv2021

Cell atlas of the regenerating human liver after portal vein embolization

The liver has the remarkable capacity to regenerate. In the clinic, this capacity can be induced by portal vein embolization (PVE), which redirects portal blood flow resulting in liver hypertrophy in locations with increased blood supply, and atrophy of embolized segments. Here we apply single-cell and single-nucleus transcriptomics on healthy, hypertrophied, and atrophied patient-derived liver samples to explore cell states in the liver during regeneration. We first establish an atlas of cell subtypes from the healthy human liver using fresh and frozen tissues, and then compare post-PVE samples with their reference counterparts. We find that PVE alters portal-central zonation of hepatocytes and endothelial cells. Embolization upregulates expression programs associated with development, cellular adhesion and inflammation across cell types. Analysis of interlineage crosstalk revealed key roles for immune cells in modulating regenerating tissue responses. Altogether, our data provides a rich resource for understanding homeostatic mechanisms arising during human liver regeneration and degeneration.

genomics↗

bioRxiv2020

TetrODrive: An open-source microdrive for combined electrophysiology and optophysiology

ObjectiveIn tetrode recordings, the cell types of the recorded units are difficult to determine based on electrophysiological characteristics alone. Optotagging, the use of optogenetic stimulation at the tip of electrodes to elicit spikes from genetically identified cells, is a method to overcome this challenge. However, recording from many different cells requires advancing electrodes and light sources slowly through the brain with a microdrive. Existing designs suffer from a number of drawbacks, such as limited stability and precision, high cost, complex assembly, or excessive size and weight. ApproachWe designed TetrODrive as a microdrive that can be 3D printed on an inexpensive desktop resin printer and has minimal parts, assembly time, and cost. The microdrive can be assembled in 15 minutes and the price for all materials, including the 3D printer, is lower than a single commercial microdrive. To maximize recording stability, we mechanically decoupled the drive mechanism from the electrical and optical connectors. Main resultsThe developed microdrive is small and light enough to be carried effortlessly by a mouse. It provides high signal-to-noise ratio recordings from optotagged units, even across recording sessions. Owing to its moveable optical fiber, our microdrive can also be used for fiber photometry. We evaluated our microdrive by recording single units and calcium signals in the ventral tegmental area (VTA) of mice and confirmed cell identity via optotagging. Thereby we found units not following the classical reward prediction error model. SignificanceTetrODrive is a tiny, lightweight, and affordable microdrive for optophysiology in mice. Its open design, price, and built-in characteristics can significantly expand the use of microdrives in mice.

neuroscience↗

bioRxiv2020

UFMylation regulates translational homeostasis and cell cycle progression

UFMylation, the posttranslational modification of proteins with ubiquitin fold modifier 1 (UFM1) is essential for metazoan life and is associated with multiple human diseases. Although UFMylation has been linked to endoplasmic reticulum (ER) stress, its biological functions and relevant cellular targets beyond the ER are obscure. Here, we show that UFMylation directly controls translation and cell division in a manner otherwise known for cellular homeostasis-sensing pathways such as mTOR. By combining cell cycle analyses, mass spectrometry and ribosome profiling we demonstrate that UFMylation is required for eIF4F translation initiation complex assembly and recruitment of the ribosome. Interference with UFMylation shuts down global translation, which is sensed by cyclin D1 and halts the cell cycle independently of integrated stress response signalling. Our findings establish UFMylation as a key regulator of translation and uncover a pathway that couples translational homeostasis to cell cycle progression via a ubiquitin-like modification.

cell biology↗

bioRxiv2019

Electrochemical Roughening and Carbon Nanotube Coating of Tetrodes for Chronic Single-Unit Recording

Recording from single neurons in the brain for long periods of time has been a central goal in both basic neuroscience and translational neurology, in order to understand mechanisms underlying brain processes such as learning and to understand the pathogenesis of neurodynamic disease states 1. Recent advances in materials engineering, digital signal acquisition, and analysis algorithms have brought us closer to achieving this goal, and the possibility has gathered much public attention 2,3. However, it remains a challenge to record from the same units for weeks to months. Here, we record many high-quality tetrode neuronal signals reliably over long periods of time in both deep and superficial areas of the brain. We achieve this by combining electrochemical roughening and carbon nanotube coating of a flexible platinum/iridium substrate, with materials, packaging, and insertion optimized to minimize tip movement with brain pulsation. This \"Magdeburger\" probe enables recordings with long-term signal stability and high signal-to-noise ratio at a reasonable cost in both rodent brains and in substantially larger primate brains. Robust tetrode tracking of identified neurons over longer time periods, in multiple independently targeted areas of the brain, will allow fundamental advances in the study of cognitive learning, aging, and pathogenesis, and opens new possibilities for brain interfaces in humans.

bioengineering↗