Biology subjects

Schwarz, C.

Publications and source records attributed to Schwarz, C..

16 recordsLinked to original sources

bioRxiv2026

Mutualisms as engines for rapid adaptation: Rhizobium evolution facilitates plant drought resistance

Mutualisms play critical roles in organismal stress tolerance; yet environmental stressors may simultaneously alter the evolution of the mutualism itself. Stress may have particularly strong impacts on the evolution of microbial mutualists due to their capacity for rapid genetic change. Here we used a legume-rhizobia mutualism, in which plants exchange carbon for symbiotically fixed nitrogen, to evaluate how mutualisms evolve in response to stressors. We experimentally evolved populations of Rhizobium leguminasarum in a full factorial design, manipulating drought and nitrogen. We quantified genomic changes in Rhizobium populations as well as their quality as partners with their plant host, Trifolium repens. Drought selected for context- dependent stress benefits to the host; drought-adapted Rhizobium strains provided increased benefits to the host under drought, but fewer benefits to the host in well-watered environments. Conversely, nitrogen fertilization selected for decreased Rhizobium partner quality. Comparative genomics indicated that selection on standing structural variants along the symbiotic plasmid may underpin these drought benefits, specifically along genes associated with desiccation tolerance. These results suggest that stress can expand the benefits rhizobia provide to their legume hosts beyond nitrogen fixation, with rapid symbiont evolution an engine in promoting adaptive plant phenotypes. SIGNIFICANCE STATEMENTWhile mutualisms are fundamental to ecosystem functioning, they are often assumed to break down under environmental stress. We showed the opposite can happen. Here, we factorially manipulated drought stress and nitrogen fertilization and experimentally evolved a model legume-rhizobia mutualism, where rhizobial-bacteria trade nitrogen for plant carbon. When droughted, the symbiotic bacteria rapidly evolved new traits that made them better partners under drought, improving plant growth within just a few generations. Evolution occurred mainly on a specialized bacterial plasmid, a mobile piece of DNA distinct from the main genome. By contrast, added nitrogen fertilizer led to decreases in bacterial benefits. These findings suggest that mutualisms are not simply fragile in the face of global change, but can expand mutualistic benefits to buffer partners against stress. CLASSIFICATIONBiological Sciences, Evolution

evolutionary biology↗

bioRxiv2026

petVAE: A Data-Driven Model for Identifying Amyloid PET Subgroups Across the Alzheimer's Disease Continuum

Amyloid-{beta} (A{beta}) PET imaging is a core biomarker and is sufficient for the biological diagnosis of Alzheimers disease (AD). Here, we aimed to identify biologically meaningful subgroups across the continuum of A{beta} accumulation using a data-driven deep learning approach, without imposing predefined thresholds for A{beta} negativity or positivity. We analyzed 3,110 A{beta} PET scans from the Alzheimers Disease Neuroimaging Initiative and Anti-Amyloid Treatment in Asymptomatic Alzheimers Disease studies to develop petVAE, a two-dimensional variational autoencoder. The model accurately reconstructed scans without prior labeling, selection by scanner or region of interest. Latent representations of scans extracted from petVAE were used to visualize and cluster the AD continuum. Clustering yielded four groups: two predominantly A{beta} negative (A{beta}-, A{beta}-+) and two predominantly A{beta} positive (A{beta}+, A{beta}++). All clusters differed in standardized uptake value ratio (p < 1.64x10-) and cerebrospinal fluid (CSF) A{beta} (p < 0.02), demonstrating petVAEs ability to assign scans along the A{beta} continuum. Extreme clusters (A{beta}-, A{beta}++) resembled conventional A{beta} negative and positive groups and differed in cognition, APOE {varepsilon}4 prevalence, A{beta} and tau CSF biomarkers (p < 3x10-). Intermediate clusters (A{beta}-+, A{beta}+) showed higher odds of carrying at least one APOE {varepsilon}4 allele versus A{beta}- (p < 0.03). Participants in A{beta}+ or A{beta}++ clusters exhibited faster progression to AD (A{beta}+ hazard ratio = 2.42, A{beta}++ HR = 9.43; p < 1.17x10-). Thus, petVAE was capable of reconstructing PET scans while extracting latent features that capture the AD continuum and define biologically meaningful subgroups, enabling data-driven characterization of preclinical disease stages.

bioinformatics↗

bioRxiv2025

Defective proviruses cause T cell reprogramming through promoter exaptation in HIV-1 infection

People living with HIV (PLWH) on antiretroviral therapy (ART) accumulate primarily defective proviral sequences in genomes of often clonally expanded CD4+ HIV-1 target cells. The majority of viral-derived DNA is transcriptionally active and preferentially found at distinct genomic loci suggesting a selective process driven by integration site-specific crosstalk between viral and host sequences. Focusing on one of the most prominent selected integration loci, the BTB Domain and CNC Homolog 2 (BACH2) gene, we here show mechanistic insights how CD4+ T cells are functionally reprogrammed via exaptation of provirus-derived regulatory sequences during long-term ART. Using a cellular model of BACH2-integrated proviruses, we find that proviral transcription drives aberrant BACH2 protein levels that escape autoregulatory feedback and impose BACH2-dependent transcriptomic changes. By mimicking these changes in primary CD4+ T lymphocytes, we observe that BACH2 drives reprogramming of cells toward a proliferative, precursor memory-like type. These reprogrammed CD4+ T cells possess traits of immune evasion and cellular survival that are signatures of persistent HIV reservoir cells in PLWH. Inhibition of provirus transcriptional activity can mitigate exaptation, suggesting a strategy to offset HIV-driven differentiation and expansion of CD4+ T cells. Finally, our data suggest that provirus exaptation at a second prominently selected proviral integration gene, the Signal Transducer And Activator of Transcription 5B (STAT5B) gene, drives a contrary, effector-like T cell fate, suggesting a multifaceted impact of exaptation on immune homeostasis. Overall, our data suggest that transcriptionally active proviruses, even if structurally defective, modulate target cells through insertional activation of integration genes, a process which we postulate to contribute to the complex immune modulation and dysregulation experienced by ART-suppressed PLWH.

microbiology↗

bioRxiv2025

Resolving the estrogen paradox in hereditary retinal degeneration: Esr1 activation suppresses Tnf-α signaling as a photoreceptor self-protection mechanism

Retinitis pigmentosa (RP) is an inherited retinal degenerative disorder characterized by progressive photoreceptor loss and irreversible blindness. Increasing evidence implicates neuroinflammation as a contributor to photoreceptor degeneration extending beyond the initial genetic insult. Although estrogen has been reported to exert anti-inflammatory effects in the central nervous system, its role in RP remains controversial, with some studies suggesting a paradoxical exacerbation of retinal pathology. To address this discrepancy, we identify estrogen receptor alpha (Esr1) as a central immunoregulatory hub in RP. Transcriptomic analyses of rd1 and rd10 revealed upregulation of estrogen-responsive and inflammatory pathways, with Esr1 expression markedly elevated during degeneration. TUNEL assays demonstrated that systemic estradiol (E2) exerted divergent effects, protective in rd1 yet deleterious in rd10, whereas selective pharmacological activation of Esr1 with propyl pyrazole triol (PPT) consistently reduced photoreceptor death, preserved dark-adapted ERG responses, and downregulated inflammatory mediators including Tnf-, Cx3cl1/Cx3cr1, Cd68, and Iba1. Mechanistically, Esr1 activation repressed microglial Tnf transcription and disrupted a self-sustaining Cx3cl1/Cx3cr1-Tnf- signaling loop driving microglial recruitment, activation and neurotoxicity in the outer nuclear layer (ONL). Targeted interventions confirmed tumor necrosis factor receptor 1 (Tnfr1) as the principal mediator of Tnf-induced photoreceptor death: selective inhibition with R7050 conferred superior protection compared with broad-spectrum Tnf- inhibitors (etanercept, infliximab). Cx3cr1 blockade likewise suppressed microglial activation and improved visual outcomes. Collectively, our findings establish Esr1 activation as not merely an external intervention but the amplification of an intrinsic self-protective program, positioning Esr1, Tnfr1, and Cx3cr1 as actionable therapeutic targets to suppress neuroinflammation and preserve vision in RP and related retinal disorders.

neuroscience↗

bioRxiv2025

Frontocentral brain networks amplify action-oriented temporal prediction errors

Successful sensorimotor behavior depends on anticipating when a tactile event will occur and translating it into rapid action, yet it remains unclear how action requirements shape temporal prediction in the human cortex. Here, we combined Magnetoencephalography (MEG), multivariate decoding and computational modeling to contrast temporally jittered finger stimulations under passive versus action-oriented conditions. We characterized a distributed frontal sensorimotor network that was linked to fast tactile-motor associations and predicted reaction-time variability. We found that trial-by-trial deviations from expected stimulus timing modulated behavior, with stronger frontocentral prediction-error encoding when an overt response was required. Temporal prediction errors were primarily encoded in a motor rather than sensory reference frame. These results reveal that action demands dynamically amplify temporal error signaling in sensorimotor circuits, in line with predictive coding frameworks postulating that the brain preferentially encodes task-relevant and goal-directed sensory prediction errors.

neuroscience↗

bioRxiv2024

A Method for the Combined Functional Assessment of Photoreceptors and Ganglion Cells in Acute Retinal Explants

Significant progress has been made in studying the individual steps of retinal signaling, yet a comprehensive understanding of the functional interplay between photoreceptors, as input cells, and retinal ganglion cells (RGCs), as output cells, remains elusive. This connection is crucial to fully unravel the retinas computational capabilities and its role in visual processing. To address this gap, this study introduces a novel technique that combines two-photon (2P) autofluorescence microscopy with multi-electrode array (MEA) recordings, enabling simultaneous testing of photoreceptor and RGC function. Unlike traditional methods that target isolated cell classes or structural analysis, this integrated technique provides the basis to investigate input-output relationships within the retinal neural network, offering a deeper understanding of its dynamic activity and adaptability to cellular dropout.

neuroscience↗

bioRxiv2024

Plasmid transmission dynamics and evolution of partner quality in a natural population of Rhizobium leguminosarum

Many bacterial traits important to host-microbe symbiosis are determined by genes carried on extrachromosomal replicons such as plasmids, chromids, and integrative and conjugative elements. Multiple such replicons often coexist within a single cell and, due to horizontal mobility, have patterns of variation and evolutionary histories that are distinct from each other and from the bacterial chromosome. In nitrogen-fixing Rhizobium, genes carried on multiple plasmids make up almost 50% of the genome, are necessary for the formation of symbiosis, and underlie bacterial traits including host plant benefits. Thus the genomics and transmission of plasmids in Rhizobium underlie the ecology and evolution of this important model symbiont. Here we leverage a natural population of clover-associated Rhizobium in which partner quality has declined in response to long-term nitrogen fertilization. We use 62 novel, reference-quality genomes to characterize 257 replicons in the plasmidome and study their genomics and transmission patterns. We find that, of the four most frequent plasmid types, two (types II & III) have more stable size, larger core genomes, and track the chromosomal phylogeny (display more vertical transmission), while others (types I & IV - the symbiosis plasmid, or pSym) vary substantially in size, shared gene content, and have phylogenies consistent with frequent horizontal transmission. We also find differentiation in pSym subtypes driven by long-term nitrogen fertilization. Our results highlight the variation in plasmid transmission dynamics within a single symbiont and implicate plasmid horizontal transmission in the evolution of partner quality. IMPORTANCEUnderstanding how bacterial genes move through natural populations is critical for understanding how bacterial traits evolve. The nitrogen-fixing bacterium Rhizobium leguminosarum lives in symbiosis with plants and is a model for studying how gene transmission from one cell to another on mobile genetic elements called plasmids impacts the evolution of bacteria and plants. Here we characterize the genomes of a natural bacterial population, then use novel approaches to show that mechanisms of plasmid gene transmission varies across multiple plasmid types possessed by R. leguminosarum. We find that changes in plasmid genes are associated with the decline of symbiotic partner quality in strains isolated from environments undergoing long-term fertilization. Together, these results underscore the importance of plasmid evolution in shaping ecosystem processes like nitrogen cycling. Our study provides a framework for probing the plasmid dynamics within natural bacterial populations and how plasmid transmission affects genetic diversity and ecological interactions in bacteria.

genomics↗

bioRxiv2024

Sputum Proteomics reveals unique signatures linked to key outcomes in cystic fibrosis trials.

RationaleLung function (FEV1) and quality of life (QoL) are key outcomes in most interventional clinical trials conducted in people living with cystic fibrosis. However, no robust pre-clinical surrogates for FEV1 and QoL exist. The precise physiological mechanisms leading to treatment-related improvements in these outcomes are incompletely understood. In this post-hoc analysis we explored the relationship between changes in the sputum proteome and these outcomes with the aim of identifying translational biomarkers. MethodsPaired sputum samples collected during the AZTEC-CF study (NCT02894684) pre and post 14 days of antibiotic treatment for an acute pulmonary exacerbation were included. Samples were analysed using in vitro Mesoscale Discovery (MSD) assays and by nano LC-MS/MS. Peptide identification and quantification was performed and the log-fold change for individual proteins and relationships between protein change and changes in FEV1 and QoL were evaluated. ResultsDistinct patterns were found between proteins that correlated with FEV1 and those that correlated with QoL improvements. FEV1 improvement was characterised by increases in bacterially-derived proteins accompanied by decreases in proteins relating to neutrophil degranulation. Conversely, changes in QoL were associated with increases in antiprotease and antioxidant proteins. MSD analysis revealed changes in some neutrophil-associated markers significantly correlated with FEV1 improvements, but no markers significantly correlated with QoL improvements. ConclusionsThese results suggest changes in two key CF clinical trial outcomes (FEV1 and QoL) may be underpinned by different physiological mechanisms. Understanding these divergent mechanisms is vital to fortify optimal clinical trial design in CF and panels of biomarkers may be needed to improve translational confidence.

immunology↗

bioRxiv2024

Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm

O_LIMouse and human pluripotent cells with multipurpose degron alleles establish versatile platforms to dissect cell type-specific functions of the pleiotropic transcription factor OTX2 C_LIO_LIOTX2 controls molecular programs required for anterior-posterior patterning of the developing gut C_LIO_LIOTX2 establishes and maintains chromatin accessibility at distinct distal gene regulatory elements in definitive endoderm C_LIO_LIOTX2 functions as a patterning factor across different germ layers and species C_LI The molecular mechanisms that drive essential developmental patterning events in the mammalian embryo remain poorly understood. To generate a conceptual framework for gene regulatory processes during germ layer specification, we analyzed transcription factor (TF) expression kinetics around gastrulation and during in vitro differentiation. This approach identified Otx2 as a candidate regulator of definitive endoderm (DE), the precursor of all gut-derived tissues. Analysis of multipurpose degron alleles in gastruloid and directed differentiation models revealed that loss of OTX2 before or after DE specification alters the expression of core components and targets of specific cellular signaling pathways, perturbs adhesion and migration programs as well as de-represses regulators of other lineages, resulting in impaired foregut specification. Key targets of OTX2 are conserved in human DE. Mechanistically, OTX2 is required to establish chromatin accessibility at candidate enhancers, which regulate genes critical to establishing an anterior cell identity in the developing gut. Our results provide a working model for the progressive establishment of spatiotemporal cell identity by developmental TFs across germ layers and species, which may facilitate the generation of gut cell types for regenerative medicine applications.

developmental biology↗

bioRxiv2023

Discerning state estimation and sensory gating, two presumptive predictive signals in mouse barrel cortex

The brain is assumed to contain distinctive predictive systems ranging from sensorimotor to cognitive functions. Here we report the successful functional delineation of two different presumptive predictive systems on the neuronal level, state estimation (SE) and sensory gating (SG), which both attenuate sensory flow during movement. Studying neuronal sensorimotor responses throughout the depth of primary somatosensory cortex in mice trained on a whisker reach task, SE appeared as a learned attenuation of tactile signal flow, due to a suppressive predictive signal, precisely at the time of an experimental sensory consequence. In contrast, SG was observable during a much longer interval after onset of the motor command. Both phenomena are internal, presumptively predictive signals, as blockade of the reafference did not affect them. We speculate that SG may be related to cognitive signals monitoring goals of movements, while SE likely is the expression of the classical notion of the reafference principle.

neuroscience↗

bioRxiv2023

ArcheD, a residual neural network for prediction of cerebrospinal fluid amyloid-beta from amyloid PET images

Detection and measurement of amyloid-beta (A{beta}) aggregation in the brain is a key factor for early identification and diagnosis of Alzheimers disease (AD). We aimed to develop a deep learning model to predict A{beta} cerebrospinal fluid (CSF) concentration directly from amyloid PET images, independent of tracers, brain reference regions or preselected regions of interest. We used 1870 A{beta} PET images and CSF measurements to train and validate a convolutional neural network ("ArcheD"). We evaluated the ArcheD performance in relation to episodic memory and the standardized uptake value ratio (SUVR) of cortical A{beta}. We also compared the brain regions relevance for the models CSF prediction within clinical-based and biological-based classifications. ArcheD-predicted A{beta} CSF values correlated strongly with measured A{beta} CSF values (r=0.81; p<0.001) and showed correlations with SUVR and episodic memory measures in all participants except in those with AD. For both clinical and biological classifications, cerebral white matter significantly contributed to CSF prediction (q<0.01), specifically in non-symptomatic and early stages of AD. However, in late-stage disease, brain stem, subcortical areas, cortical lobes, limbic lobe, and basal forebrain made more significant contributions (q<0.01). Considering cortical gray matter separately, the parietal lobe was the strongest predictor of CSF amyloid levels in those with prodromal or early AD, while the temporal lobe played a more crucial role for those with AD. In summary, ArcheD reliably predicted A{beta} CSF concentration from A{beta} PET scans, offering potential clinical utility for A{beta} level determination and early AD detection.

neuroscience↗

bioRxiv2022

Unexpected finding of Fusobacterium varium abundance in cattle rumen: implications for liver abscess interventions

Fusobacterium varium has been generally overlooked in cattle rumen microbiome studies relative to the presumably more abundant, liver abscess-causing Fusobacterium necrophorum. Here, we revisit that conventional wisdom and report greater relative abundance of F. varium than F. necrophorum in both raw rumen samples and in lactate-supplemented enrichments tailored for F. necrophorum growth, despite its consistent inadvertence in past ruminal surveys and putative inability to metabolize lactate. Our observation that F. varium grows under restrictive conditions used to enumerate F. necrophorum suggests that previous estimations were inaccurate and F. varium is an underestimated player within the ruminal community. Exposure to tylosin, the current gold standard among prophylactic liver abscess prevention strategies in cattle, consistently reduced growth of all F. necrophorum strains screened by greater than 67% relative to unexposed controls. In contrast, F. varium strains were completely or highly resistant (0 - 11% reduction in maximum yield). Monensin, an ionophore fed to cattle to improve feed efficiency also had stronger inhibitory activity against F. necrophorum than against F. varium. Finally, preliminary genomic analysis of two F. varium bovine isolates revealed the presence of virulence genes related to those of pathogenic F. varium human isolates associated with active invasion of mammalian cells. ImportanceJudicious antibiotic use is essential to mitigate the spread of antimicrobial resistance. Dogmatic prophylactic use of in-feed tylosin to control cattle liver abscesses hinges on the assumption that F. necrophorum in the rumen is the main etiologic agent. However, our unexpected finding of abundance of F. varium in the rumen and its resistance to antibiotics, in hand with the potential pathogenicity of this species, calls for increased attention to F. varium. Further investigation into F. varium is necessary to better understand bovine liver abscess development and devise higher-precision alternatives to antibiotic treatment.

microbiology↗

bioRxiv2022

Protective role of podocytic IL-15/STAT5 pathway in experimental focal and segmental glomerulosclerosis

During glomerular diseases, podocyte-specific pathways can modulate the intensity of the lesions and prognosis. The therapeutic targeting of these pathways could thus improve the management and prognosis of chronic kidney diseases. The Janus Kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) pathway, classically described in immune cells, has been recently described in intrinsic kidney cells. Here, we show, for the first time, that STAT5 is activated in human podocytes in focal segmental glomerulosclerosis (FSGS). Additionally, Stat5 podocyte-specific inactivation aggravates the functional and structural alterations in a mouse model of FSGS. This could be due, at least in part, to an inhibition of the autophagic flux. Finally, Interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes and its administration alleviates glomerular injury in vivo by maintaining the autophagy flux in podocytes. In conclusion, activating podocytic STAT5 with commercially available IL-15 represents a new therapeutic avenue with the potential for FSGS.

pathology↗

bioRxiv2021

Genetic diversification of persistent Mycobacterium abscessus within Cystic Fibrosis patients

Mycobacterium (M.) abscessus infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on M. abscessus genomic evolvement during chronic lung infection would be beneficial for improving treatment strategies. A longitudinal study enrolling 42 CF patients was performed at a CF center in Berlin, Germany, to elaborate phylogeny and genomic diversification of in-patient M. abscessus. Eleven of the 42 CF patients were infected with M. abscessus. Global human-transmissible M. abscessus cluster strains were isolated from five of these 11 patients. Phylogenetic analysis of 88 genomes from isolates of the 11 patients excluded occurrence of M. abscessus transmission among members of the study group. Genome sequencing and variant analysis of 30 isolates from 11 serial respiratory samples collected over four years from a chronically infected patient demonstrated accumulation of gene mutations. In total, 53 genes exhibiting non-synonymous variations were identified. Enrichment analysis emphasized genes involved in synthesis of glycopeptidolipids, genes from the embABC (arabinosyltransferase) operon, betA (glucose-methanol-choline oxidoreductase) and choD (cholesterol oxidase). Genetic diversity evolved in a variety of virulence- and resistance-associated genes. The strategy of M. abscessus populations in chronic lung infection is not clonal expansion of dominant variants, but to sustain simultaneously a wide range of genetic variants facilitating adaptation of the population to changing living conditions in the lung. Genomic diversification during chronic infection requires increased attention when new control strategies against M. abscessus infections are explored.

genomics↗

bioRxiv2019

HUMANS USE A LOCAL CODE FOR TACTILE PERCEPTION

Humans are classically thought to use either spectral decomposition or averaging to identify vibrotactile signals. These are general purpose global codes that require integration of the signal over long stretches of time. Natural vibrotactile signals, however, likely contain short signature events that can be detected and used for inference of textures, instantaneously, with minimal integration, suggesting a hitherto ignored local code. Here, by employing pulsatile stimuli and a change detection psychophysical task, we studied whether humans make use of local cues. We compared three local cues based on instantaneous skin position and its derivatives, as well as six global cues, calculated as summed powers (with exponents 1,2, and 3) of velocity and acceleration. Deliberate manipulation of pulse width and amplitude (local+global) as well as pulse frequency (global) allowed us to disentangle local from global codes. The results singled out maximum velocity, an instantaneous code, as a likely and dominant coding variable that humans rely on to perform the task. Comparing stimuli containing versus lacking local cues, demonstrated that performances exclusively using global cues are rather poor compared to situations where local ones are available as well. Our results are in line with the notion that humans not only do use local cues but that local cues may even play a dominant role in perception. Our results parallel previous results in rodents, pointing to the possibility that quite similar coding strategies evolved in whisker and finger tactile systems. Significance statementThe brain is believed to select coding symbols in sensory signals that would most efficiently convey functionally relevant information about the world. For instance, the visual system is widely believed to use spatially local features, like edge orientation, to delineate a visual scene. For the tactile system only global, general purpose coding schemes have been discussed so far. Based on the insight that moving contacts, characteristic for active touch, feature short-lived stick-slip events, frictional movements that transfer fair amounts of texture information, one should expect the brain to use a temporally local code, extracting and instantaneously analyzing short snippets of skin movement. Here, we provide the first analytical psychophysical evidence in humans that this indeed is the case.

neuroscience↗

bioRxiv2019

Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

The optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz light pulses led to a reversed sign of BOLD - indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of fMRI to elucidate the brain-wide network activation in response to projection-specific optogenetic stimulation.

neuroscience↗