Biology subjects

Schmid, M. C.

Publications and source records attributed to Schmid, M. C..

8 recordsLinked to original sources

bioRxiv2025

Effect of fluid control on the affective state of laboratory macaques

Fluid control protocols are widely used in neuroscience to motivate laboratory macaques to engage with behavioural tasks. Despite strong evidence that the physiology of the animals is not compromised by such protocols, fluid control remains controversial due to its potential impact on the psychological well-being of the animals. To address this concern, we investigated the effect of fluid control on the affective state of 23 socially-housed adult macaques (10 females) engaged in neuroscience experiments. The protocol involved up to five consecutive days of fluid control per week, followed by a minimum of two days with unrestricted fluid access. The affective state of the animals was primarily assessed by quantifying the frequency of pharmacologically-validated behavioural indicators of high-arousal negative affect (self-scratching, body shaking, self-grooming). The analysis was subsequently extended to validated behavioural indicators of low-arousal negative affect (Inactive not alert) and other behaviours suspected of indicate high-arousal negative affect but lacking proper validation (pacing, yawning). In total, 700 hours of video footage spanning up to seven years of intermittent fluid control per animal were analysed. Despite this extensive dataset, the study found no significant impact of fluid control on average, or any evidence of habituation or sensitization over the years on any of the affective state indicators. Additional results indicate that these null results are not due to a lack of sensitivity, supporting the view that fluid control, as implemented in this study, does not have an adverse impact on the psychological well-being of laboratory macaques. We argue that macaque welfare will be best served by focusing future refinement on other procedures.

animal behavior and cognition↗

bioRxiv2021

Stimulus dependence of theta rhythmic activity in primate V1 and its potential relevance for visual perception

Theta-band (3-8 Hz) neural oscillations are integral to sensory processing and active exploration. Traditionally associated with higher-order areas such as hippocampus and prefrontal cortex, recent studies identified theta rhythmic modulations in the primary visual cortex (V1) of mice during locomotion, suggesting sensory processing functions. Here, we demonstrate that careful optimization of visual stimulus size and contrast can induce robust theta oscillations in macaque V1. During visual detection, monkeys reaction times fluctuated rhythmically at the theta frequency of V1 neural activity, with detection performance correlated to the theta phase. These findings suggest that induced theta oscillations may reflect an intrinsic temporal filtering mechanism of V1 neurons, highlighting the importance of early sensory cortical dynamics in shaping perceptual timing.

neuroscience↗

bioRxiv2021

Optogenetic stimulation of primate V1 reveals local laminar and large-scale cortical networks related to perceptual phosphenes

Developing optogenetics in non-human primates (NHPs) is essential for translating its successful implementation in rodents to clinical applications in humans. However, information about how optogenetics influences the primate cortex remains limited. Here, we evaluate how optogenetic stimulation of the primate primary visual cortex (V1) affects local and large-scale network activation concerned with visual perception. To this end we injected an optogenetic construct (AAV9-hSyn-ChR2-eYFP) into the V1 cortex of four macaque monkeys (macaca mulatta) and measured the effects of optogenetic V1 stimulation using functional magnetic resonance imaging (fMRI), laminar electrophysiology, and behavioural assessment. In three macaques, blood-oxygen-dependent (BOLD) fMRI activity could be reliably elicited with optogenetic stimulation in V1 and several connected extrastriate brain areas, including V2/V3, motion-sensitive area MT and the frontal-eye-fields (FEF), in particular when pulsed stimulation at 40 Hz was applied. BOLD modulation was associated with consistent neural spiking activity measured in V1 of two macaques. More detailed analysis revealed strongest neuronal activation in layer 4B and infragranular layers, which tightly reflected the histological expression pattern of the optogenetic construct in V1. Driving this visual network proved sufficient to elicit a visual percept ( phosphene) in one macaque during a perceptual choice task. Taken together, our findings reveal the laminar and large-cortical activation pattern related to visual phosphene generation and emphasize the need for further improving optogenetic methods in NHPs as a step towards applications in humans.

neuroscience↗

bioRxiv2021

Dynamic reconfiguration of macaque brain networks during free-viewing of natural scenes

Natural vision involves the activation of a wide range of higher-level regions processing objects, motion, faces and actions. Here, we pursue a data-driven approach to explore how higher-level visual processes relate to the underlying structural and functional connectivity. Using a free-viewing paradigm in four awake rhesus macaque monkeys, we investigate how different visual scenes change functional connectivity. Additionally, we explore how such functional connectivity, as measured through fMRI, is related to the structural connectivity, as measured through diffusion weighted imaging. At first, we evaluate the consistency of the elicited free-viewing pattern using standard analytical techniques. We also evaluate the underlying structural connectivity via diffusion data by tracking white matter bundle projections from the visual cortex. We then reconstruct free-viewing and structural networks and quantify their properties. Centrality measures over the entire fMRI time-series revealed a consistent functional network engaged during free-viewing that included widespread hub regions across frontal (FEF, 46v), parietal (LIP, Tpt), and occipitotemporal cortex (MT, V4 and TE) among others. Interestingly, a small number of highly-weighted and long-length inter-hemispheric connections indicated the presence of long-range integrative properties during free-viewing. We hypothesized that during free-viewing, networks had the capacity to change their local and distal connections depending on the on-going changes in visual scenes. To capture these network dynamics, we depart from the static modular architecture of the structural networks and demonstrate that hubs in free-viewing networks reorganize according to the presence of objects, motion, and faces in the movie scenes indicating poly-functional properties. Lastly, we compare each NHP subject network and observe high consistency between individuals across the same network type with closer correspondence between structural networks (e.g., diffusion based and those partially assembled from tract-tracing). In summary, our network analyses revealed ongoing changes in large-scale functional organization present during free-viewing in the macaque monkey and highlight the advantages of multi-contrast imaging in awake monkeys for investigating dynamical processes in visual cognition. To further promote the use of naturalistic free-viewing paradigms and increase the development of macaque neuroimaging resources, we share our datasets in the PRIME-DE consortium.

neuroscience↗

bioRxiv2020

Stimulus-specific plasticity of macaque V1 spike rates and gamma

When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here we show in awake macaque area V1 that both, repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects showed some persistence on the timescale of minutes. Further, gamma increases were specific to the presented stimulus location. Importantly, repetition effects on gamma and on firing rates generalized to natural images. These findings suggest that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters, both for generating efficient stimulus responses and possibly for memory formation.

neuroscience↗

bioRxiv2019

Blockade of stromal Gas6 alters cancer cell plasticity, activates NK cells and inhibits pancreatic cancer metastasis.

Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers due to its aggressive and metastatic nature. PDA is characterized by a rich tumor stroma with abundant macrophages, fibroblasts and collagen deposition that can represent up to 90% of the tumor mass. Activation of the tyrosine kinase receptor AXL and expression of its ligand growth arrest-specific protein 6 (Gas6) correlate with a poor prognosis and increased metastasis in pancreatic cancer patients. Gas6 is a multifunctional protein that can be secreted by several cell types and regulates multiple processes, including cancer cell plasticity, angiogenesis and immune cell functions. However, the role of Gas6 in pancreatic cancer metastasis has not been fully investigated. In these studies we find that, in pancreatic tumors, Gas6 is mainly produced by tumor associated macrophages (TAMs) and cancer associated fibroblasts (CAFs) and that pharmacological blockade of Gas6 partially reverses epithelial-to-mesenchymal transition (EMT) of tumor cells and supports NK cell activation, thereby inhibiting pancreatic cancer metastasis. Our data suggest that Gas6 simultaneously acts on both the tumor cells and the NK cells to support pancreatic cancer metastasis. This study supports the rationale for targeting Gas6 in pancreatic cancer and use NK cells as a potential biomarker for response to anti-Gas6 therapy.

cancer biology↗

bioRxiv2018

Resolving the individual contribution of key microbial populations to enhanced biological phosphorus removal with Raman-FISH

Enhanced biological phosphorus removal (EBPR) is a globally important biotechnological process and relies on the massive accumulation of phosphate within special microorganisms. Candidatus Accumulibacter conform to classical physiology model for polyphosphate accumulating organisms and are widely believed to be the most important player for the process in full-scale EBPR systems. However, it was impossible till now to quantify the contribution of specific microbial clades to EBPR. In this study, we have developed a new tool to directly link the identity of microbial cells to the absolute quantification of intracellular poly-P and other polymers under in situ conditions, and applied it to eight full-scale EBPR plants. Besides Ca. Accumulibacter, members of the genus Tetrasphaera were found to be important microbes for P accumulation, and in six plants they were the most important. As these Tetrasphaera cells did not exhibit the classical phenotype of poly-P accumulating microbes, our entire understanding of the microbiology of the EBPR process has to be revised. Furthermore, our new single-cell approach can now also be applied to quantify storage polymer dynamics in individual populations in situ in other ecosystems and might become a valuable tool for many environmental microbiologists.

ecology↗

bioRxiv2018

Rhythmic neural spiking and attentional samplingarising from cortical receptive field interactions

Growing evidence suggests that distributed spatial attention may invoke theta (3-9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is however not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields elicits rhythmic multi-unit activity (MUA) at 3-6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RT) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at at theta frequencies. These findings suggest that theta-rhythmic neuronal activity arises from competitive receptive field interactions and that this rhythm may subserve attentional sampling.\n\nHighlightsO_LICenter-surround interactions induce theta-rhythmic MUA of visual cortex neurons\nC_LIO_LIThe MUA rhythm does not depend on small fixational eye movements\nC_LIO_LIReaction time fluctuations lock to the neuronal rhythm under distributed attention\nC_LI

neuroscience↗