Biology subjects

Schoch, S.

Publications and source records attributed to Schoch, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Single-cell profiling reveals tumor grade-dependent immune remodeling in BRAFV600E-driven glioneuronal tumors

BRAFV600E is the key driver variant in epilepsy-associated glioneuronal tumors (GNTs). These tumors often share MAPK/PI3K hyperactivation, a generally benign biological course and rare occurrence of malignant variants. We aimed to characterize the poorly defined immune cell milieu of GNTs with distinct biological behavior. We mapped cellular heterogeneity of the tumor microenvironment (TME) using single-cell transcriptomics on murine models of low-grade (LG-GNT; BRAFV600E/AKTA) and high-grade (HG-GNT; BRAFV600E/AKTA/Trp53KO) tumors, generated via intraventricular in utero electroporation (IUE). Furthermore, ex vivo functional assays with CSF1R-mediated myeloid depletion were utilized to assess the role of identified signaling molecules on tumor viability. We observed a striking, grade-dependent immunological dichotomy: LG-GNT exhibited a permissive niche with prominent surveillance by T cells and pro-inflammatory microglia. In contrast, HG-GNT TME was characterized by a restricted T cell infiltration, massively dominated by myeloid cell infiltrates. Differential gene expression analysis identified Spp1 (osteopontin) as a key mediator of this immunosuppressive HG-GNT TME, exclusively expressed in microglia and border-associated macrophages (BAMs). Crucially, ex vivo functional assays demonstrated that recombinant SPP1 enhances tumor viability through a paracrine mechanism. These findings suggest fundamentally distinct immune activation (a) stimulated by aberrant MAPK/PI3K signaling in LG-GNT, versus (b) malignant tumor feature-driven, e.g. through necrosis in HG-GNT. In the latter, SPP1 signaling creates the immunosuppressive niche. Consequently, while modulating the pro-inflammatory niche may mitigate tumor-related epileptogenicity in LG-GNTs, targeting the SPP1-myeloid axis may restore anti-tumor immunity in HG-GNTs.

neuroscience↗

bioRxiv2025

HIF1α-dependent induction of the T-Type calcium channel CaV3.2 mediates hypoxia-induced neuronal hyperexcitability

Post-stroke epilepsy (PSE) is a leading cause of acquired epilepsy in adults, yet the molecular mechanisms linking post-ischemic hypoxia to neuronal hyperexcitability remain poorly understood. The transcription factor hypoxia-inducible factor 1 (HIF1) is a central mediator of the cellular response to hypoxia and may contribute to epileptogenesis by regulating ion channel expression. Here, we identify the T-type calcium channel CaV3.2 (encoded by Cacna1h) as a direct transcriptional target of HIF1 and demonstrate its role in hypoxia-induced network hyperexcitability. Oxygen-glucose deprivation followed by reoxygenation (OGD/R) induced a persistent increase in neuronal firing rate. In murine and human organotypic brain slices, hypoxia led to a marked increase in HIF1 and Cacna1h expression at both transcript and protein levels. Using neuronal cell lines and primary cortical neurons we show that HIF1 activation through HIF1 overexpression, consistently increases Cacna1h expression. In NS20Y cells, overexpression of a normoxia-stable HIF1 variant increased Cacna1h promoter activity in both fluorescent and dual-luciferase reporter assays. The same effect was observed in primary cortical neurons, where HIF1 overexpression also elevated network activity measured by multielectrode array recordings, replicating the effect of the OGD/R model. Together, these results establish HIF1 as a key transcriptional regulator of CaV3.2 in neurons and reveal a conserved hypoxia-HIF1-CaV3.2 pathway that enhances neuronal excitability. This mechanism may underlie hypoxia-induced network hyperactivity and contribute to the pathogenesis of post-ischemic epileptogenesis, offering a potential molecular target for intervention.

neuroscience↗

bioRxiv2025

Stool Dynamics and the Developing Gut Microbiome During Infancy

The infant gut microbiome is a dynamic ecosystem that plays a crucial role in early development, influences immune system maturation, and overall health. Recent insights reveal that the gut microbiota undergoes changes across the 24-h day, raising the possibility that it may act as "zeitgeber", helping to regulate the hosts sleep-wake organisation. Despite its importance, timing factors influencing microbiome composition are poorly understood, limiting its use as a health predictor. This study investigates the relationship between stool dynamics (interval since last defecation, collection time of the sample), sleep pressure (interval since last sleep), meal timing and the composition of the gut microbiome. Stool samples from 198 healthy infants, aged 3 to 31 months, were analysed to assess microbial diversity, richness evenness, and abundance. Our findings reveal that longer intervals since the last bowel movement are associated with increased microbial diversity, evenness, and richness. Stool timing is associated with shifts in microbial composition, especially in younger infants, indicating that diurnal microbial fluctuations may become more stable as infants mature. We found that longer periods of wakefulness were associated with increased microbial diversity in early infancy, although this effect appeared to diminish with age. Feeding schedules appeared to have a limited effect on the gut microbiome. Longer fasting before sampling showed no significant associations with most microbial parameters, except for a positive association with microbial richness. At the phylum level, results indicate that infant gut microbial composition is influenced by behaviour and physiology. Longer intervals between bowel movements were associated with shifts in bacterial abundance, with Proteobacteria decreasing and Actinobacteria increasing. Stool timing and meal timing also affected microbial diversity: later sampling times showed higher Actinobacteria levels, and longer fasting was associated with reduced Bacteroidetes. Sleep pressure showed a trend effect with Firmicutes displaying a slight decrease in infants who had been awake longer. Our findings underscore the importance of time-based factors on infant gut microbiome composition.

systems biology↗

bioRxiv2025

Rhythms of Early Life: Gut Microbiota Rhythmicity and Circadian Maturation in infants

BackgroundThe human gut microbiota undergoes daily fluctuations, yet its interaction with sleep-wake patterns during infancy remains largely uncharted. This study aims to elucidate the relationship between gut microbiota rhythmicity and the development of sleep patterns in infants over the first year of life. We continuously monitored 162 healthy infants across multiple days at 3, 6, and 12 months of age using ankle actigraphy and 24-hour diaries. The Circadian Function Index (CFI) was computed as a proxy for sleep-wake rhythm maturation. Stool samples were collected to profile gut microbiota taxa composition via 16S rRNA gene amplicon sequencing, and microbial oscillations were assessed through sine and cosine fitting to detect 24-hour patterns. ResultsOur findings revealed that the relative abundance of bacterial taxa exhibited rhythmic patterns, with 26 zOTUs (1.74%) following a sine pattern and 100 zOTUs (6.69%) displaying cosine rhythmicity. Cosine rhythmicity became more pronounced with age, showing strong maturation: 7 zOTUs at 3 months, 2 zOTUs at 6 months, and 86 zOTUs at 12 months. Notably, 105 zOTUs (7.02%) were associated with CFI, demonstrating a significant relationship between gut microbiota rhythms and sleep development. Among these, 27 zOTUs with sine dynamics and 96 zOTUs with cosine dynamics were linked to CFI, with this association strengthening as infants aged. ConclusionsThese results highlight the increasing synchronization between gut microbiota rhythmicity and sleep-wake cycles during infancy, pointing to a critical window for potential health interventions. This novel observation, previously reported in rodents and adults, underscores the role of gut microbiota in early human development, offering new avenues for enhancing developmental outcomes through targeted interventions.

developmental biology↗

bioRxiv2024

DNA methylation is a key determinant of response to targeted and immune checkpoint therapies in metastatic renal cell carcinoma

The response to targeted therapies and immune checkpoint inhibitors for patients suffering from metastatic clear cell renal cell carcinoma (ccRCC) is heterogeneous and currently not predictable in clinic. In this work, a comprehensive integrated study of 700 ccRCCs profiled by DNA methylation and RNA sequencing showed that the hyper-methylated tumors exhibited a worse prognosis, a higher fraction of cycling tumor cells and a lower activity of homeobox transcription factors. To translate the use of DNA methylation information into a clinical setting, we developed a simple model accurately predicting the ccRCC methylation subtypes (AUC-ROCs of 0.91) from two gene expression ratios (IGF2BP3/PCCA, TNNT1/TMEM88). In addition, these methylation subtypes were significantly associated with the therapeutic outcome of patients to anti-PD-1, mTOR inhibitor or tyrosine kinase inhibitor therapies. Overall, our framework for predicting the ccRCC DNA methylation subtypes from targeted gene expression data is easy to translate in clinic and contributes to better personalization of ccRCC therapies.

bioinformatics↗

bioRxiv2024

A fluorescent biosensor for the visualization of agmatine

Agmatine is known to regulate various neurotransmitter systems, yet the underlying molecular mechanisms remain elusive. To visualize agmatine dynamics in cellular networks and thereby unravel its physiological functions, we developed a genetically encoded fluorescent agmatine biosensor (AGMsen) based on the periplasmic putrescine binding protein PotF. We first analyzed the agmatine binding properties of the PotF receptor module based on its crystal structure and introduced mutations into the binding pocket to favor agmatine binding over other biogenic amines. Validation of AGMsen functionality across different cell types, including primary neuronal cultures, demonstrates its ability of real-time agmatine visualization. Thus, the sensor can serve as a valuable tool to advance our understanding of agmatine distribution and dynamics, and shed light on their effect on neuronal functions in vivo.

biochemistry↗

bioRxiv2024

Highly effective verified lucid dream induction using combined cognitive-sensory training and wearable EEG: a multi-centre study

Lucid dreaming occurs when one is aware of dreaming while asleep. While lucid dreaming can occur spontaneously, it remains rare. This multi-center study (Netherlands, Italy, Canada) tested a combined induction approach integrating senses-initiated lucid dreaming (SSILD) with targeted lucidity reactivation in a large sample of participants with varying lucid dreaming experience. Sixty participants (33 F; 26.5 {+/-}6.2 years old) completed two morning naps in the sleep laboratory. Participants received pre-sleep SSILD training paired with visual, auditory, and tactile cues that were then reintroduced in REM sleep, with stimulation and sham conditions counterbalanced. Lucidity and cue perception were verified using intentional eye movements from within the dream (signal-verified lucid dream, SVLD). SVLDs occurred in 31 participants (51.7%) across both naps. Subjective lucidity occurred in 63 naps (52.5%), including 40 SVLDs (33.3%) with no difference between stimulation (38.3%) and sham (28.3%) conditions. However, SVLD duration and number of predefined eye movements were higher with sensory cueing. Cues were perceived within sleep in most cued REM periods (71.1%), sometimes acting as lucidity signals (39.1% of stim SVLDs) and occasionally disrupting sleep (23.7% of cued periods). Overall, our combined cognitive-sensory induction method produced relatively high lucid dreaming rates, even in participants who rarely experience them. While cues were sometimes perceived as lucidity signals and may help prolong lucid episodes, our results do not show clear benefits of REM cueing over SSILD training alone. Further refinement of these methods may support clinical applications and deepen insight into consciousness and sensory processing during sleep.

neuroscience↗

bioRxiv2023

A missense mutation (C667F) in beta-dystroglycan results in reduced dystroglycan protein levels leading to myopathy and destabilization of the blood-brain and blood-retinal barrier protein network

Dystroglycan (DG) is a glycoprotein and extracellular matrix receptor consisting of an -DG and a {beta}-DG subunit encoded by the gene DAG1. A homozygous missense mutation (c.2006G>T), resulting in an amino acid substitution (p.Cys669Phe) in the extracellular domain of {beta}-DG, causes severe Muscle-Eye-Brain disease with multicystic leukodystrophy. To investigate the mechanisms underlying the severe human pathology, we generated a mouse model of this primary dystroglycanopathy. We find that homozygous mutant mice show no obvious abnormalities during development and reach mature adulthood. However, - and {beta}-DG protein levels are significantly downregulated in muscle and brain of homozygous mutant mice. The mutant mice show a form of myopathy with late-onset and not fully penetrant histopathological changes in skeletal muscle and are impaired in their performance on an activity wheel. The brain and eyes of the homozygous mutant mice appear to be structurally normal, but the localization of mutant {beta}-DG is altered in the glial perivascular endfeet (PVE) at the blood-brain- and blood-retina barrier resulting in a perturbed protein composition in the PVE. In conclusion, the mouse model of the C669F {beta}-DG mutation does not seem to recapitulate the severe developmental phenotypes observed in human patients but represents a novel and highly valuable tool to study the impact of {beta}-DG functional changes at the molecular level and to gain insight into the pathogenesis of primary dystroglycanopathies.

pathology↗

bioRxiv2023

Microenvironment of metastatic site reveals key predictors of PD-1 blockade response in renal cell carcinoma

Immune checkpoint blockade (ICB) therapies have improved the overall survival (OS) of many patients with advanced cancers. However, the response rate to ICB varies widely among patients, exposing non-responders to potentially severe immune-related adverse events. The discovery of new biomarkers to identify patients responding to ICB is now a critical need in the clinic. We therefore investigated the tumor microenvironment (TME) of advanced clear cell renal cell carcinoma (ccRCC) samples from primary and metastatic sites to identify molecular and cellular markers of response to ICB. We revealed a significant discrepancy in treatment response between subgroups based on cell fractions inferred from metastatic sites. One of the subgroups was enriched in non-responders and harbored a lower fraction of CD8+ T cells and plasma cells, as well as a decreased expression of immunoglobulin genes. In addition, we developed the Tumor-Immunity Differential (TID) score which combines features from tumor cells and the TME to accurately predict response to anti-PD-1 immunotherapy (AUC-ROC=0.88, log-rank tests for PFS P < 0.0001, OS P = 0.01). Finally, we also defined TID-related genes (YWHAE, CXCR6 and BTF3), among which YWHAE was validated as a robust predictive marker of ICB response in independent cohorts of pre- or on-treatment biopsies of melanoma and lung cancers. Overall, these results provide a rationale to further explore variations in the cell composition of metastatic sites, and underlying gene signatures, to predict patient response to ICB treatments. One Sentence SummaryTumor microenvironment balance of metastasis and associated genes are key predictors of immunotherapy patient response in kidney cancer.

bioinformatics↗

bioRxiv2022

Synaptic vesicle-bound molecular bridges organize sequential vesicle states along parallel pathways

Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, and structural studies of purified systems were essential for our understanding of the function of the individual complexes involved, they cannot combine high structural detail with the unperturbed organization of complexes within cells to resolve how the actions of individual complexes integrate. We employed cryo-electron tomography to simultaneously image multiple presynaptic protein complexes and lipids at molecular resolution in their native composition, conformation and environment. Our results argue that tethers comprising proteins Munc13 and SNAP25 differentially and spatially confine vesicles with single nanometer precision, define vesicle tethering states, and provide molecular mechanisms that guide vesicles towards fusion, which includes molecular priming by conversion to SNARE complex-dependent tethers. These findings present an example of a cellular function performed by an extended molecular assembly comprising multiple, molecularly diverse complexes.

neuroscience↗

bioRxiv2022

Ultrastructural analysis of wildtype and RIM1α knock-out active zones in a large cortical synapse

Rab3A-interacting molecule (RIM) is crucial for fast Ca2+-triggered synaptic vesicle (SV) release in presynaptic active zones (AZ). While loss of RIM1 impairs long-term plasticity at hippocampal giant mossy fiber boutons (MFB), it remains unclear how AZ ultrastructure is altered. We investigated MFB AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1-/- and wild-type mice. In RIM1-/-, AZs are larger with increased synaptic cleft heights and with a three-fold reduced number of tightly docked SVs (0-2nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1-/- is more heterogeneous. Thus, RIM1, beside its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.

neuroscience↗

bioRxiv2021

A versatile CRISPR toolbox to study neurological CaV3.2 channelopathies by promoter-mediated transcription control

Precise genome editing in combination with viral delivery systems provides a valuable tool for neuroscience research. Traditionally, the role of genes in neuronal circuits has been addressed by overexpression or knock-out/knock-down systems. However, those techniques do not manipulate the endogenous loci and therefore have limitations. Those constraints include that many genes exhibit extensive alternative splicing, which can be regulated by neuronal activity. This complexity cannot be easily reproduced by overexpression of one protein variant. The CRISPR activation and interference/inhibition systems (CRISPRa/i) directed to promoter sequences can modulate the expression of selected target genes in a highly specific manner. This strategy could be particularly useful for the overexpression of large proteins and for alternatively spliced genes, e.g. for studying large ion channels known to be affected in ion channelopathies in a variety of neurological diseases. Here, we demonstrate the feasibility of a newly developed CRISPRa/i toolbox to manipulate the promoter activity of the Cacna1h gene. Impaired, function of the low-voltage-activated T-Type calcium channel CaV3.2 is involved in genetic/mutational as well as acquired/transcriptional channelopathies that emerge with epileptic seizures. We show CRISPR-induced activation and inhibition of the Cacna1h locus in NS20Y cells and primary cortical neurons, as well as activation in mouse organotypic slice cultures. In future applications, the system offers the intriguing perspective to study functional effects of gain-of-function or loss-of-function variations in the Cacna1h gene in more detail. A better understanding of CaV3.2 channelopathies might result in a major advancement in the pharmacotherapy of CaV3.2 channelopathy diseases.

neuroscience↗

bioRxiv2021

Heterogeneity and excitability of BRAFV600E-induced tumors is determined by PI3K/mTOR-signaling state and Trp53-loss

BackgroundDevelopmental brain tumors harboring BRAFV600E somatic mutation are diverse. Here, we describe molecular factors that determine BRAFV600E-induced tumor biology and function. MethodsIntraventricular in utero electroporation in combination with the piggyBac transposon system is employed as a tool to generate developmental brain neoplasms. In vivo tumor growth is monitored by using the infrared fluorescent protein (iRFP). Lineage inference is carried out by using the Brainbow transgene. Neural activity from tumor slices is assessed by multielectrode array. RNA sequencing is exploited to analyze the induced neoplasms at the transcriptomic level. ResultsBRAFV600E in murine neural progenitors only in concert with active PI3K/mTOR-signaling through constitutively phosphorylated Akt-kinase (pAkt) elicits benign neoplasms composed of enlarged dysmorphic neurons and neoplastic astroglia recapitulating ganglioglioma (GG). Purely glial tumors partially resembling polymorphous low-grade neuroepithelial tumors of the young (PLNTYs) emerge from BRAFV600E alone. Additional somatic Trp53-loss is sufficient to induce anaplastic GGs (aGGs) with glioneuronal clonality. Functionally, only BRAFV600E/pAkt tumors intrinsically generate substantial neuronal activity and show enhanced relay to adjacent tissue conferring high epilepsy propensity. In contrast, PLNTY- and aGG-models lack significant spike activity, which appears in line with the glial differentiation of the former and a dysfunctional tissue structure combined with reduced neuronal transcript signatures in the latter. ConclusionmTOR-signaling and Trp53-loss critically determine the biological diversity and electrical activity of BRAFV600E-induced tumors. Key pointsO_LIIUE of BRAFV600E and activation of mTOR leads to ganglioglioma (GG)-like tumors, while BRAFV600E alone give rise to PLNTY-like neoplasms. C_LIO_LIAnaplastic GGs depend on the Trp53 deletion in combination to BRAFV600E and PI3K-mTOR signaling cascade. C_LI Importance of the StudyGlioneuronal tumors are challenging with respect to biological behavior and seizure emergence. While BRAFV600E in murine neural precursors induces oligoid tumors, it requires an overactivation of PI3K/mTOR-signaling for the development of hyperexcitable gangliogliomas and additional Trp53-loss for anaplastic transformation.

neuroscience↗

bioRxiv2021

Leaky wiring of the brain: local cluster of coupled synapses and extracellular signal integration

The wiring scheme of neurons is key to the function of the brain. Neurons are structurally wired by synapses and it is a long-held view that most synapses in the CNS are sufficiently isolated to avoid cross-talk to AMPA receptors of neighboring synapses. Here we report in hippocampal brain slices that quantal glutamate release activated optical reporter proteins >1.5 {micro}m distant to the releasing synapse. 2P-glutamate uncaging was used to quantitatively probe glutamate spread in the neuropil. Releasing [~]35000 molecules of glutamate ([~]5 vesicles) at a distance of 500 nm to a spine generated an uncaging EPSC reaching [~]30% of the quantal amplitude at synaptic AMPA-Rs. The same stimulus activated [~]70% of the quantal amplitude at NMDA-Rs and still generated clear current and calcium responses when applied at >= 2 {micro}m remote to the spine. Extracellular spread of glutamate on the sub-micrometer scale appeared cooperative and caused supra-additive activation of AMPA-Rs in a spine. These observations are not predicted by previously used models of glutamate diffusion in the neuropil. An extracellular glutamate scavenger system weakly reduced field potential responses but not the quantal amplitude, indicating that a cross-talk component regularly contributes to synaptic transmission. Our data suggest that slight synaptic crosstalk responses at AMPA receptors of [~]2-4 adjacent synapses may be common (>70 synapses for NMDA receptors). Such broadcasting of synaptic signals to very local neighborhoods could stabilize network learning performance and allow for integration of synaptic activity within the extracellular space.

neuroscience↗

bioRxiv2020

Ste20-like kinase is critical for inhibitory synapse maintenance and its deficiency confers a developmental dendritopathy

The size and structure of the dendritic arbor play important roles in determining how synaptic inputs of neurons are converted to action potential output. The regulatory mechanisms governing the development of dendrites, however, are insufficiently understood. The evolutionary conserved Ste20/Hippo kinase pathway has been proposed to play an important role in regulating the formation and maintenance of dendritic architecture. A key element of this pathway, Ste20-like kinase (SLK), regulates cytoskeletal dynamics in non-neuronal cells and is strongly expressed throughout neuronal development. However, its function in neurons is unknown. We show that during development of mouse cortical neurons, SLK has a surprisingly specific role for proper elaboration of higher, [≥] 3rd, order dendrites. Moreover, we demonstrate that SLK is required to maintain excitation-inhibition balance. Specifically, SLK knockdown caused a selective loss of inhibitory synapses and functional inhibition after postnatal day 15, while excitatory neurotransmission was unaffected. Finally, we show that this mechanism may be relevant for human disease, as dysmorphic neurons within human cortical malformations revealed significant loss of SLK expression. Overall, the present data identify SLK as a key regulator of both dendritic complexity during development and of inhibitory synapse maintenance.

neuroscience↗

bioRxiv2018

Actimetry in infant sleep research: an approach to facilitate comparability

Study ObjectivesOnly standardized objective assessments reliably capture the large variability of sleep behavior in infancy, which is the most pronounced during the human lifespan. This is important for clinical as well as basic research. Actimetry is a cost-efficient method to objectively track infant sleep/wake behavior by assessing limb movements. Nevertheless, the standardization of actimetry-based sleep/wake measures is limited by two factors: the use of different computational approaches and the bias towards measuring only nighttime sleep - neglecting [~]20 % of sleep infants obtain during daytime.\n\nMethodsWe used actimetry in 50 infants for 10 continuous days at ages 3, 6 and 12 mo in a longitudinal approach. We analyzed the infants sleep/wake behaviors applying with two commonly used algorithms: Sadeh and Oakley/Respironics. We compared minute-by-minute agreement and Kappa between the two algorithms, as well as the algorithms with sleep/wake measures from a comprehensive 24-hour, parent-reported diary.\n\nResultsAgreement between uncorrected algorithms was moderate (77 - 84%). By introducing a 6-step adjustment, we increased agreement between algorithms (96 - 97%) and with the diary. This decreased the difference between the two algorithms in e.g. Total Sleep Duration from 4.5 h to 0.2 h.\n\nConclusionsThis computational pipeline enhances comparability between infant actimetry studies and the inclusion of parent-reported diaries allows the integration of daytime sleep. Objectively assessed infant sleep that is comparable across different studies supports the establishment of normative developmental trajectories and clinical cutoffs.

neuroscience↗

bioRxiv2018

Memory trace superimposition impairs recall in a mouse model of AD

Learning and memory processes depend on the hippocampus and are impaired in Alzheimers disease (AD). Active neuronal ensembles form an engram by encoding information during learning. Their reactivation is required for memory recall. However, it remains unresolved whether the engram in CA1 principal neurons is impaired under AD-like conditions. We used two-photon in vivo imaging to visualize the expression of the immediate early gene c-fos within CA1 neurons during contextual fear conditioning and retrieval. Surprisingly, we identified engrams in wild-type mice and in the mouse model of AD indicating intact memory formation. However, under AD-like conditions engrams were superimposed by a high number of newly recruited fosGFP+ neurons during memory recall. This superimposition resembled the network configuration of wild-type mice exposed to a novel context. Artificial superimposition of the memory trace during recall in wild-type mice was sufficient to induce memory impairment. Thus, we propose superimposition of the CA1 memory trace as a mechanism for memory impairment in a mouse model of AD.\n\nHighlightsO_LIDecreased fosGFP expression in direct vicinity to amyloid-{beta} plaques\nC_LIO_LIIntact engram in CA1 of APP/PS1 mice\nC_LIO_LIImpurity of the retrieval network in CA1 is sufficient to impair memory recall\nC_LI\n\nPoll et al. present a novel mechanism for memory impairment in a mouse model of AD. The potential memory trace was found intact in the CA1 region of the hippocampus. However, excessive neuronal activity during retrieval, was superimposing the memory trace in a mouse model of AD.

neuroscience↗

bioRxiv2018

The effect of dream report collection and dream incorporation on memory consolidation during sleep

Waking up during the night to collect dream reports is a commonly used method to study dreams. This method has also been applied in studies on the relationship between dreams and memory consolidation. However, it is unclear if these awakenings influence ongoing memory consolidation processes. Furthermore, only few studies have examined if task incorporation into dreams is related to enhanced performance in the task. Here we compare memory performance in a word-picture association learning task after a night with (up to six awakenings) and without awakenings in 22 young and healthy participants. We then examine if the task is successfully incorporated into the dreams and if this incorporation is related to the task performance the next morning. We show that while the awakenings impair both subjective and objective sleep quality, these awakenings did not impair ongoing memory consolidation during sleep. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. No incorporation occurred in dreams collected only in the morning. Task incorporation into NREM sleep dreams, but not REM sleep dreams showed a relationship with task performance the next morning.\n\nWe conclude that the method of awakenings to collect dream reports is suitable for dream and memory studies, and is even crucial to uncover task incorporations. Furthermore, our study suggests that dreams in NREM rather than REM sleep might be related to processes of memory consolidation during sleep.

neuroscience↗