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Meyer, A. F.

Publications and source records attributed to Meyer, A. F..

7 recordsLinked to original sources

COLLEMBOT: AI-Based Counting of Collembola for OECD 232 Tests

Ecotoxicological tests with soil organisms, such as the collembolan Folsomia candida, are essential for assessing chemical risks in terrestrial ecosystems. However, the current Organization for Economic Co-operation and Development (OECD) 232 reproduction tests rely on manual counting of juvenile and adult Collembola, a process that is costly, labor-intensive, time-consuming and prone to operator bias. These limitations restrict data availability and hinder robust risk assessments. We therefore developed COLLEMBOT, an automated counting tool based on a YOLOv11 convolutional neural network, designed to integrate seamlessly into OECD workflows without protocol modifications. The model was trained on high-resolution images (n = 3207) from multiple laboratories and validated using 22 independent datasets (n = 1704 images) from Amsterdam (Netherlands), Basel (Switzerland), Bayreuth (Germany), Coimbra (Portugal) and Aarhus (Denmark). Datasets consisted of relevant standard soils (OECD artificial soils with 2.5%, 5% and 10% sphagnum peat; LUFA 2.2) and the springtail Folsomia candida. Automated counts showed strong agreement with manual counts (R{superscript 2} = 0.88-0.99). Dose-response curves derived from automated and manual counts strongly overlapped and effect concentrations (EC and EC) differed minimally (Median %{Delta} 6.2 {+/-} 23 and EC10 - EC90 R2 [≥] 0.977), remaining within acceptable limits for regulatory risk assessment and confirming reliability. Time efficiency improved significantly: a test with [~]300 images and up to 1,500 individuals per image was processed in less than 3 hours, compared to [~]137 hours needed for manual counting, a reduction of approximately 97%. By reducing labor and improving reproducibility, COLLEMBOT enables broader hazard data generation for collembolans, supporting science-based chemical risk assessment. The code and workflow are publicly available to facilitate adoption and community-driven development. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/697653v1_ufig1.gif" ALT="Figure 1"> View larger version (131K): org.highwire.dtl.DTLVardef@1d3ddc5org.highwire.dtl.DTLVardef@84c90aorg.highwire.dtl.DTLVardef@1aaf06aorg.highwire.dtl.DTLVardef@18ddfcd_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Pathogenic bacteria secrete protein effectors to hijack host machinery and remodel their infectious niche. Rickettsia spp. are obligate intracellular bacteria that can cause life- threatening disease, but their absolute dependence on the host cell environment has impeded discovery of rickettsial effectors and their host targets. We implemented bioorthogonal non-canonical amino acid tagging (BONCAT) during R. parkeri infection to selectively label, isolate, and identify secreted effectors. As the first use of BONCAT in an obligate intracellular bacterium, our screen more than doubles the number of experimentally validated effectors for R. parkeri. The novel secreted rickettsial factors (Srfs) we identified include Rickettsia-specific proteins of unknown function that localize to the host cytoplasm, mitochondria, and ER. We further show that one such effector, SrfD, interacts with the host Sec61 translocon. Altogether, our work uncovers a diverse set of previously uncharacterized rickettsial effectors and lays the foundation for a deeper exploration of the host-pathogen interface.

microbiology↗

Contextual modulation is a stable feature of the neural code in auditory cortex of awake mice

The perceptual salience of a sound depends on the acoustic context in which it appears, and can vary on a timescale of milliseconds. At the level of single neurons in the auditory cortex, spectrotemporal tuning for particular sounds is shaped by a similarly fast and systematic nonlinear sensitivity to acoustic context. Does this neuronal context sensitivity "drift" over time in awake animals, or is it a stable feature of sound representation in the auditory cortex? We used chronically implanted tetrode arrays in awake mice to measure the electrophysiological responses of auditory cortical neurons to spectrotemporally complex, rapidly varying sounds across many days. For each neuron in each recording session, we applied the nonlinear-linear "context model" to estimate both a principal (spectrotemporal) receptive [fi]eld and a "contextual gain [fi]eld" describing the neurons nonlinear sensitivity to acoustic context. We then quanti[fi]ed the stability of these [fi]elds within and across days, using spike waveforms to match neurons recorded in multiple sessions. Contextual gain [fi]elds of auditory cortical neurons in awake mice were remarkably stable across many days of recording, and comparable in stability to principal receptive [fi]elds. Interestingly, there were small but signi[fi]cant effects of changes in locomotion or pupil size on the ability of the context model to [fi]t temporal fluctuations in the neuronal response. We conclude that both spectrotemporal tuning and nonlinear sensitivity to acoustic context are stable features of neuronal sound representation in the awake auditory cortex, which can be modulated by behavioral state.

neuroscience↗

The Hybrid Drive: a chronic implant device combining tetrode arrays with silicon probes for layer-resolved ensemble electrophysiology in freely moving mice

Understanding the function of brain cortices requires simultaneous investigation at multiple spatial and temporal scales and to link neural activity to an animals behavior. A major challenge is to measure within- and across-layer information in actively behaving animals, in particular in mice that have become a major species in neuroscience due to an extensive genetic toolkit. Here we describe the Hybrid Drive, a new chronic implant for mice that combines tetrode arrays to record within-layer information with silicon probes to simultaneously measure across-layer information. The design of our device combines up to 14 tetrodes and 2 silicon probes, that can be arranged in custom arrays to generate unique areas-specific (and multi-area) layouts. We show that large numbers of neurons and layer-resolved local field potentials can be recorded from the same brain region across weeks without loss in electrophysiological signal quality. The drives lightweight structure ({approx} 3.5 g) leaves animal behavior largely unchanged during a variety of experimental paradigms. We demonstrate how the data collected with the Hybrid Drive allow state-of-the-art analysis in a series of experiments linking the spiking activity of CA1 pyramidal layer neurons to the oscillatory activity across hippocampal layers. Our new device fits a gap in the existing technology and increases the range and precision of questions that can be addressed about neural computations in freely behaving mice.

neuroscience↗

Two distinct types of eye-head coupling in freely moving mice

Animals actively interact with their environment to gather sensory information. There is conflicting evidence about how mice use vision to sample their environment. During head restraint, mice make rapid eye movements strongly coupled between the eyes, similar to conjugate saccadic eye movements in humans. However, when mice are free to move their heads, eye movement patterns are more complex and often non-conjugate, with the eyes moving in opposite directions. Here, we combined eye tracking with head motion measurements in freely moving mice and found that both observations can be explained by the existence of two distinct types of coupling between eye and head movements. The first type comprised non-conjugate eye movements which systematically compensated for changes in head tilt to maintain approximately the same visual field relative to the horizontal ground plane. The second type of eye movements were conjugate and coupled to head yaw rotation to produce a "saccade and fixate" gaze pattern. During head initiated saccades, the eyes moved together in the same direction as the head, but during subsequent fixation moved in the opposite direction to the head to compensate for head rotation. This "saccade and fixate" pattern is similar to that seen in humans who use eye movements (with or without head movement) to rapidly shift gaze but in mice relies on combined eye and head movements. Indeed, the two types of eye movements very rarely occurred in the absence of head movements. Even in head-restrained mice, eye movements were invariably associated with attempted head motion. Both types of eye-head coupling were seen in freely moving mice during social interactions and a visually-guided object tracking task. Our results reveal that mice use a combination of head and eye movements to sample their environment and highlight the similarities and differences between eye movements in mice and humans. HighlightsO_LITracking of eyes and head in freely moving mice reveals two types of eye-head coupling C_LIO_LIEye/head tilt coupling aligns gaze to horizontal plane C_LIO_LIRotational eye and head coupling produces a "saccade and fixate" gaze pattern with head leading the eye C_LIO_LIBoth types of eye-head coupling are maintained during visually-guided behaviors C_LIO_LIEye movements in head-restrained mice are related to attempted head movements C_LI

animal behavior and cognition↗

Hearing loss promotes schizophrenia-relevant brain and behavioral abnormalities in a mouse model of human 22q11.2 Deletion Syndrome

Hearing loss has been implicated as a risk factor for schizophrenia, but it is not known whether this association arises from common etiology, top-down influences (e.g., social isolation), bottom-up neurobiological mechanisms, or combinations of these factors. Patients with 22q11.2 Deletion Syndrome (22q11.2DS) have a 25-30% risk of developing schizophrenia, and also suffer frequent hearing loss. Here, we used the Df1/+ mouse model of 22q11.2DS to investigate the relationship between hearing loss and susceptibility to schizophrenia-relevant brain and behavioral abnormalities. Df1/+ mice have a multi-gene deletion analogous to the chromosomal microdeletion that causes human 22q11.2DS, and like human 22q11.2DS patients exhibit high rates of hearing loss arising primarily from susceptibility to middle ear inflammation. We found that hearing loss in Df1/+ mice affected schizophrenia-relevant endophenotypes, including electrophysiological measures of central auditory gain and behavioral measures of auditory sensorimotor gating. Moreover, PV+ inhibitory interneurons, another marker for schizophrenia pathology, were significantly reduced in density in auditory cortex but not secondary motor cortex of Df1/+ mice with hearing loss. These results reveal bottom-up neurobiological mechanisms through which peripheral hearing loss arising from the 22q11.2 deletion may promote the emergence of schizophrenia-relevant auditory brain and behavioral abnormalities, and also suggest a link between conductive hearing loss and reduced PV+ interneuron density in the auditory cortex. SIGNIFICANCE STATEMENTHearing loss is a known risk factor for schizophrenia. Deletion of chromosomal locus 22q11.2 is associated with both schizophrenia and hearing loss in humans. In the Df1/+ mouse model of human 22q11.2 Deletion Syndrome, we find that hearing loss shapes measures that are considered schizophrenia-relevant endophenotypes, such as central auditory gain and auditory sensorimotor gating. Moreover, we report a reduction in density of PV+ inhibitory interneurons in the auditory cortex, but not secondary motor cortex, of Df1/+ mice with hearing loss. These results suggest mechanisms through which hearing loss associated with the 22q11.2 deletion may promote emergence of schizophrenia-relevant auditory brain and behavioral abnormalities and indicate that conductive hearing loss may influence PV+ interneuron density in the auditory cortex.

neuroscience↗

An ultralight head-mounted camera system integrates detailed behavioral monitoring with multichannel electrophysiology in freely moving mice

Breakthroughs in understanding the neural basis of natural behavior require neural recording and intervention to be paired with high-fidelity multimodal behavioral monitoring. An extensive genetic toolkit for neural circuit dissection, and well-developed neural recording technology, make the mouse a powerful model organism for systems neuroscience. However, methods for high-bandwidth acquisition of behavioral signals in mice remain limited to fixed-position cameras and other off-animal devices, complicating the monitoring of animals freely engaged in natural behaviors. Here, we report the development of an ultralight head-mounted camera system combined with head-movement sensors to simultaneously monitor eye position, pupil dilation, whisking, and pinna movements along with head motion in unrestrained, freely behaving mice. The power of the combined technology is demonstrated by observations linking eye position to head orientation; whisking to non-tactile stimulation; and, in electrophysiological experiments, visual cortical activity to volitional head movements.

neuroscience↗