bluuebunny/crossref_metadata_2025 huggingface dataset:
Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification
Authors: Yoo Sangjin , Mittelstein David R. , Hurt Robert , Lacroix Jerome , Shapiro Mikhail G.
Published: May 2020

Ultrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, the biomolecular and cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for the use of this technology in research and potential clinical applications. Here, we show that focused ultrasound excites neurons through a primarily mechanical mechanism mediated by specific calcium-selective mechanosensitive ion channels. The activation of these channels results in a gradual build-up of calcium, which is amplified by calcium- and voltage-gated channels, generating a burst firing response. Cavitation, temperature changes, large-scale deformation, and synaptic transmission are not required for this excitation to occur. Pharmacological and genetic inhibition of specific ion channels leads to reduced responses to ultrasound, while over-expressing these channels results in stronger ultrasonic stimulation. These findings provide a critical missing explanation for the effect of ultrasound on neurons and facilitate the further development of ultrasonic neuromodulation and sonogenetics as unique tools for neuroscience research.
Microbial diversity of the glass spongeVazella pourtalesiiin response to anthropogenic activities
Authors: Busch Kathrin , Beazley Lindsay , Kenchington Ellen , Whoriskey Frederick , Slaby Beate , Hentschel Ute
Published: May 2020

Establishment of adequate conservation areas represents a challenging but crucial task in the conservation of genetic diversity and biological variability. Anthropogenic pressures on marine ecosystems and organisms are steadily increasing. Whether and to what extent these pressures influence marine genetic biodiversity is only starting to be revealed. Using 16S rRNA gene amplicon sequencing, we analysed the microbial community structure of 33 individuals of the habitat-forming glass spongeVazella pourtalesii, as well as reference seawater, sediment, and biofilm samples. We assessed how two anthropogenic impacts, i.e. habitat destruction by trawling and artificial substrate provision (moorings made of composite plastic), correspond within situ V. pourtalesiimicrobiome variability. In addition, we evaluated the role of two bottom fishery closures in preserving sponge-associated microbial diversity on the Scotian Shelf, Canada. Our results illustrate thatV. pourtalesiisponges collected from pristine sites within fishery closures contained distinct and taxonomically largely novel microbial communities. At the trawled site we recorded significant quantitative differences in distinct microbial phyla, such as a reduction in Nitrospinae in sponges and environmental references. Individuals ofV. pourtalesiigrowing on the mooring were significantly enriched in Bacteroidetes, Verrucomicrobia and Cyanobacteria in comparison to sponge individuals growing on the natural seabed. Due to a concomitant enrichment of these taxa in the mooring biofilm, we propose that biofilms on artificial substrates may ‘prime’ sponge-associated microbial communities when small sponges settle on such substrates. These observations likely have relevant management implications when considering the increase of artificial substrates in the marine environment, e.g., marine litter, off-shore wind parks, and petroleum platforms.
Portable Take-Home System Enables Proportional Control and High-Resolution Data Logging with a Multi-Degree-of-Freedom Bionic Arm
Authors: Brinton Mark , Barcikowski Elliott , Davis Tyler , Paskett Michael , George Jacob , Clark Gregory
Published: May 2020

This paper describes a portable, prosthetic control system for at-home use of an advanced bionic arm. The system uses a modified Kalman filter to provide 6 degree-of-freedom, real-time, proportional control. We describe (a) how the system trains motor control algorithms for use with an advanced bionic arm, and (b) the system’s ability to record an unprecedented and comprehensive dataset of EMG, hand positions and force sensor values. Intact participants and a transradial amputee used the system to perform activities-of-daily-living, including bi-manual tasks, in the lab and at home. This technology enables at-home dexterous bionic arm use, and provides a high-temporal resolution description of daily use—essential information to determine clinical relevance and improve future research for advanced bionic arms.
Dismantling and rebuilding the trisulfide cofactor demonstrates its essential role in human sulfide quinone oxidoreductase
Authors: Landry Aaron P. , Moon Sojin , Bonanata Jenner , Cho Uhn Soo , Coitiño E. Laura , Banerjee Ruma
Published: May 2020

Sulfide quinone oxidoreductase (SQR) catalyzes the first step in sulfide clearance, coupling H2S oxidation to coenzyme Q reduction. Recent structures of human SQR revealed a sulfur atom bridging the SQR active site cysteines in a trisulfide configuration. Here, we assessed the importance of this cofactor using kinetic, crystallographic and computational modeling approaches. Cyanolysis of SQR proceeds via formation of an intense charge transfer complex that subsequently decays to eliminate thiocyanate. Cyanolysis leads to reversible loss of SQR activity, which is restored in the presence of sulfide. We captured a crystallographic intermediate in SQR that provides clues as to how the oxidized state of the cysteines is preserved. Computational modeling and MD simulations revealed an ~105-fold rate enhancement for nucleophilic addition of sulfide into the trisulfide versus a disulfide cofactor. The cysteine trisulfide in SQR is thus critical for activity and provides a significant catalytic advantage over a cysteine disulfide.
The role of the hypothalamus in cortical arousal and sleep homeostasis
Authors: Yamagata Tomoko , Kahn Martin C. , Šabanović Merima , Guillaumin Mathilde C.C. , van der Vinne Vincent , Huang Yi-Ge , McKillop Laura E. , Jagannath Aarti , Peirson Stuart N. , Mann Edward O. , Foster Russell G. , Vyazovskiy Vladyslav V.
Published: May 2020

Sleep and wakefulness are not simple homogenous all-or-none states, but instead are characterized by rich dynamics of brain activity across many temporal and spatial scales. Rapid global state transitions between waking and sleeping are believed to be controlled by hypothalamic circuits, but the contribution of the hypothalamus to within-state changes of sleep and wake “intensity” remains largely unexplored. Here we show that stimulation of inhibitory neurons in the preoptic hypothalamus does not merely trigger awakening from sleep, but the resulting awake state is also characterized by increased cortical activity. This activation is associated with a faster build-up of sleep pressure, proportional to the arousal level. These findings show that hypothalamic systems thought to exclusively control global state switching, also regulate within-state “intensity”, which we propose as a key intrinsic variable in shaping the architecture of sleep/wake states across the 24h day.
Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress
Authors: Santana Jose M. Santiago , Vega-Torres Julio David , Ontiveros Angel Perla , Lee Jeong Bin , Torres Yaria Arroyo , Gonzalez Alondra Y. Cruz , Aponte Boria Esther , Zabala Ortiz Deisha , Carmona Carolina Alvarez , Figueroa Johnny D.
Published: May 2020

Background

There is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid diet-induced obesity and stress-induced anxiety to neuroinflammation and oxidative stress.

Methods

Thirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3) Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE). Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearson’s correlation procedures.

Results

We found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185%), catalase protein (215%), and glutathione reductase (GSR) enzymatic activity (418%) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety.

Conclusions

Together, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations.

Highlights

Predatory odor stress heightens footshock reactivity and anxiety-like behaviors in Lewis rats.

WD intake increases glutathione reductase activity in plasma.

WD intake and PS exposure acted synergistically to increase the brain protein levels of catalase and the glial fibrillary acidic protein.

The protein levels and activities of some redox/neuroinflammatory biomarkers are closely associated with behavioral proxies related to fear and anxiety in rats.
Coxsackievirus B3 Infection Early in Pregnancy Induces Congenital Heart Defects Through Suppression of Fetal Cardiomyocyte Proliferation
Authors: Sharma Vipul , Goessling Lisa S. , Brar Anoop K. , Joshi Chetanchandra S. , Mysorekar Indira U. , Eghtesady Pirooz
Published: May 2020

Aims

Coxsackievirus B (CVB), the most common cause of viral myocarditis, targets cardiomyocytes through Coxsackie and Adenovirus Receptor, which is highly expressed in the fetal heart. We hypothesized CVB3, a well-recognized culprit for viral myocarditis, can precipitate congenital heart defects (CHD), when fetal infection occurs during critical window of gestation.

Methods & Results

We infected C57Bl/6 pregnant mice with CVB3 during serial time points in early gestation (E5, E7, E9 and E11). We used different viral titers to examine possible dose- response relationship and assessed viral loads in various fetal organs as well as kinetics of virus passage into the fetus during gestation. Provided viral exposure occurred between E7-E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling non-compaction (23.5%), and double outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers, severity and incidence of CHD, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of CHD. We examined signaling pathways in CVB3-exposed hearts using RNAseq, KEGG enrichment analysis and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor β1 and extracellular matrix proteins were the most highly enriched in CVB3-infected fetuses with VSD (log fold change >1.9, P<0.02). Moreover, cardiomyocyte proliferation was 50% lower in fetuses with VSD compared with uninfected controls.

Conclusion

Prenatal CVB3 infection can induce CHD, provided the infection occurs during a critical window. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for the majority of observed phenotypes.

GRAPHICAL ABSTRACT
Time course of alterations in adult spinal motoneuron properties in the SOD1(G93A) mouse model of ALS
Authors: Huh Seoan , Heckman Charles J. , Manuel Marin
Published: May 2020

Although ALS is an adult-onset neurodegenerative disease, motoneuron electrical properties are already altered during embryonic development. Motoneurons must therefore exhibit a remarkable capacity for homeostatic regulation to maintain a normal motor output for most of the life of the patient. In the present paper, we demonstrate how maintaining homeostasis could come at a very high cost. We studied the excitability of spinal motoneurons from young adult SOD1(G93A) mice to end-stage. Initially homeostasis is highly successful in maintaining their overall excitability. This initial success, however, is achieved by pushing some cells far above the normal range of passive and active conductances. As the disease progresses, both passive and active conductances shrink below normal values in the surviving cells. This shrinkage may thus promote survival, implying the previously large values contribute to degeneration. These results support the hypothesis that motoneuronal homeostasis may be “hyper-vigilant” in ALS and a source of accumulating stress.

Significance Statement

During ALS, motoneurons exhibit a remarkable ability to maintain a normal motor output despite continuous alterations of their electrophysiological properties, up to the point when overt symptoms become apparent. We show that this homeostatic process can sometimes push motoneurons beyond the normal range, which may be causing long-lasting harm.
Deep learning for automated analysis of fish abundance: the benefits of training across multiple habitats
Authors: Ditria Ellen , Sievers Michael , Lopez-Marcano Sebastian , Jinks Eric L. , Connolly Rod M.
Published: May 2020

Environmental monitoring guides conservation, and is thus particularly important for coastal aquatic habitats, which are heavily impacted by human activities. Underwater cameras and unmanned devices monitor aquatic wildlife, but manual processing of footage is a significant bottleneck to rapid data processing and dissemination of results. Deep learning has emerged as a solution, but its ability to accurately detect animals across habitat types and locations is largely untested for coastal environments. Here, we produce three deep learning models using an object detection framework to detect an ecologically important fish, luderick (Girella tricuspidata). Two were trained on footage from single habitats (seagrass or reef), and one on footage from both habitats. All models were subjected to tests from both habitat types. Models performed well on test data from the same habitat type (object detection measure: mAP50: 91.7 and 86.9% performance for seagrass and reef, respectively), but poorly on test sets from a different habitat type (73.3 and 58.4%, respectively). The model trained on a combination of both habitats produced the highest object detection results for both tests (92.4 and 87.8%, respectively). Performance in terms of the ability for models to correctly estimate the ecological metric, MaxN, showed similar patterns. The findings demonstrate that deep learning models extract ecologically useful information from video footage accurately and consistently, and can perform across habitat types when trained on footage from the variety of habitat types.
The Cognitive Mechanisms That Drive Social Belief Updates During Adolescence
Authors: Ma I. , Westhoff B. , van Duijvenvoorde A.C.K.
Published: May 2020

Adolescence is a key life phase for developing well-adjusted social behaviour. Belief updates about the trustworthiness of peers are essential during adolescence as social reorientation emerges and peer relationships intensify. This study maps the age-related changes of those belief updates during adolescence (n= 157, 10-24 years). We used computational modelling and an information sampling paradigm to reveal that three cognitive mechanisms contribute to age-related changes in those belief updates: prior beliefs, prior uncertainty, and uncertainty tolerance. The age-related changes in these three cognitive mechanisms result in increasingly adaptive belief updates from early to mid-adolescence when it comes to beliefs about trustworthiness. Our findings shed light on age-related changes in adaptive learning about others during adolescence.
Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate Major Depressive from Generalized Anxiety Disorder
Authors: Xu Xiaolei , Dai Jing , Chen Yuanshu , Liu Congcong , Xin Fei , Zhou Xinqi , Zhou Feng , Stamatakis Emmanuel A , Yao Shuxia , Luo Lizhu , Huang Yulan , Wang Jinyu , Zou Zhili , Vatansever Deniz , Kendrick Keith M , Zhou Bo , Becker Benjamin
Published: May 2020

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. The present study combined categorial and dimensional disorder models with a fully data-driven intrinsic network level analysis (Intrinsic Connectivity Contrast, ICC) to resting state fMRI data acquired in 108 partn = 35 and n = 38 unmedicated patients with first-episode GAD, MDD respectively and n=35 healthy controls). Convergent evidence from categorical and dimensional analyses revealed MDD-specific decreased whole-brain connectivity profiles of the medial prefrontal and dorsolateral prefrontal cortex while GAD was specifically characterized by decreased whole-brain connectivity profiles of the putamen and decreased communication of this region with the amygdala. Together, findings from the present data-driven analysis suggest that intrinsic communication of frontal regions engaged in executive functions and emotion regulation represent depression-specific neurofunctional markers and treatment targets whereas dysregulated intrinsic communication of the striato-amygdala system engaged in reinforcement-based and emotional learning processes represent GAD-specific markers and a promising treatment target.
Transcriptional and epigenetic characterization of early striosomes identifies Foxf2 and Olig2 as factors required for development of striatal compartmentation and neuronal phenotypic differentiation
Authors: Cirnaru Maria-Daniela , Song Sicheng , Tshilenge Kizito-Tshitoko , Corwin Chuhyon , Mleczko Justyna , Aguirre Carlos Galicia , Benlhabib Houda , Bendl Jaroslav , Apontes Pasha , Fullard John F. , Muncunill Jordi Creus , Reyah Azadeh , Nik Ali M. , Carlsson Peter , Roussos Panos , Mooney Sean D. , Ellerby Lisa M. , Ehrlich Michelle E.
Published: May 2020

The basal ganglia, best known for processing information required for multiple aspects of movement, is also part of a network which regulates reward and cognition. The major output nucleus of the basal ganglia is the striatum, and its functions are dependent on neuronal compartmentation, including striosomes and matrix, which are selectively affected in disease. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), all of which share basic molecular signatures but are subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating terminal neuronal differentiation following migration are largely unidentified. We performed RNA- and ATAC-seq on sorted murine striosome and matrix cells at postnatal day 3. Focusing on the striosomal compartment, we validated the localization and role of transcription factors and their regulator(s), previously not known to be associated with striatal development, includingIrx1, Foxf2, Olig2andStat1/2. In addition, we validated the enhancer function of a striosome-specific open chromatin region located 15Kb downstream of theOlig2gene. These data and data bases provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation and thus provide new approaches to establishing MSN subtypes from human iPSCs for disease modeling and drug discovery.
Purifying selection on noncoding deletions of human regulatory elements detected using their cellular pleiotropy
Authors: Radke David W. , Sul Jae Hoon , Balick Daniel J. , Akle Sebastian ,   Alzheimer’s Disease Neuroimaging Initiative, Green Robert C. , Sunyaev Shamil R.
Published: May 2020

Genomic deletions provide a powerful loss-of-function model in non-coding regions to assess the role of purifying selection on human noncoding genetic variation. Regulatory element function is char-acterized by non-uniform tissue/cell-type activity, necessarily linking the study of fitness consequences from regulatory variants to their corresponding cellular activity. We used deletions from the 1000 Genomes Project (1000GP) and a callset we generated from genomes of participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in order to examine whether purifying selection preserves noncoding sites of chromatin accessibility (DHS), histone modification (enhancer, transcribed, polycomb-repressed, heterochromatin), and topologically associated domain loops (TAD-loops). To examine this in a cellular activity-aware manner, we developed a statistical method, Pleiotropy Ratio Score (PlyRS), which calculates a correlation-adjusted count of “cellular pleiotropy” for each noncoding base-pair by analyzing shared regulatory annotations across tissues/cell-types. Comparing real deletion PlyRS values to simulations in a length-matched framework and using genomic covariates in analyses, we found that purifying selection acts to preserve both DHS and enhancer sites, as evident by both depletion of deletions overlapping these annotations and a shift in the allele frequency spectrum of overlapping deletions towards rare alleles. However, we did not find evidence of purifying selection for transcribed, polycomb-repressed, or heterochromatin sites. Additionally, we found evidence that purifying selection is acting on TAD-loop boundary integrity by preserving co-localized CTCF binding sites. Notably, at regions of DHS, enhancer, and CTCF within TAD-loop boundaries we found evidence that both sites of tissue/cell-type-specific activity and sites of cellularly pleiotropic activity are preserved by selection.

Significance Statement

We used natural genomic deletions as a loss-of-function model to assess the role of purifying selection in preserving human noncoding regulatory sites. We examined this in a cellular activity-aware manner through development of a statistical method, Pleiotropy Ratio Score (PlyRS), which calculates an adjusted count of “cellular pleiotropy” for each noncoding basepair by analyzing correlations from shared regulatory annotations across tissues/cell-types. By comparing real deletion PlyRS values to simulations, we found that purifying selection acts to preserve both DHS and enhancer sites and TAD-loop boundary integrity by preserving co-localized CTCF binding sites. Notably, we found evidence at these regulatory regions that both sites of tissue/cell-type-specific activity and sites of cellularly pleiotropic activity are preserved by selection.
Color constancy based on the geometry of color distribution
Authors: Morimoto Takuma , Kusuyama Takahiro , Fukuda Kazuho , Uchikawa Keiji
Published: May 2020

A white surface appears white under different lighting environments. This ability is referred to color constancy. The physical inputs to our visual system are dictated by the interplay between lights and surfaces, and thus for the surface color to be stably perceived, the illuminant influence needs to be discounted. To reveal our strategy to infer the illuminant color, we conducted three psychophysical experiments designed to test optimal color hypothesis: we internalize the physical color gamut under a particular illuminant and apply the prior to estimate the illuminant color. In each experiment, we presented 61 hexagons arranged without spatial gaps, where the surrounding 60 hexagons were set to have a specific shape in their color distribution. We asked participants to adjust the color of a center test field so that it appears a full-white surface placed under a test illuminant. Results and computational modeling suggested that although our proposed model is limited in accounting for estimation of illuminant intensity by human observers, it agrees fairly well with the estimates of illuminant chromaticity in most tested conditions. The accuracy of estimation generally outperformed other tested conventional color constancy models. These results support the hypothesis that our visual system can utilize the geometry of scene color distribution to achieve color constancy.
Central amygdala mineralocorticoid receptors modulate alcohol self-administration
Authors: Makhijani Viren H. , Irukulapati Preethi , Van Voorhies Kalynn , Fortino Brayden , Besheer Joyce
Published: May 2020

The mineralocorticoid receptor (MR) is an emerging target in the field of alcohol research. The MR is a steroid receptor in the same family as the glucocorticoid receptor, with which it shares the ligand corticosterone in addition to the MR selective ligand aldosterone. Recent studies have shown correlations between central amygdala (CeA) MR expression and alcohol drinking in rats and macaques, as well as correlations between aldosterone and alcohol craving in individuals with alcohol use disorder (AUD). Additionally, our previous work demonstrated that systemic treatment with the MR antagonist spironolactone reduced alcohol self-administration and response persistence in both male and female rats. This study examined if reductions in self-administration following MR antagonist treatment were related to dysregulation of MR-mediated corticosterone negative feedback. Female rats treated with spironolactone (50 mg/kg; IP) showed increased plasma corticosterone following self-administration which correlated with reduced alcohol self-administration. Next, local microinjection of the MR-selective antagonist eplerenone was used to identify the brain-regional locus of MR action on alcohol self-administration. Eplerenone infusion produced dose-dependent reductions in alcohol self-administration in the CeA, but had no effect in the dorsal hippocampus. Finally, to assay the functional role of CeA MR expression in alcohol self-administration, CeA MR was knocked down by antisense oligonucleotide (ASO) infusion prior to alcohol self-administration. Rats showed a transient reduction in alcohol self-administration 1 day after ASO infusion. Together these studies demonstrate a functional role of CeA MR in modulating alcohol self-administration and make a case for studying MR antagonists as a novel treatment for AUD.
Genome analysis of the fatal tapewormSparganum proliferumunravels the cryptic lifecycle and mechanisms underlying the aberrant larval proliferation
Authors: Kikuchi Taisei , Dayi Mehmet , Hunt Vicky L. , Toyoda Atsushi , Maeda Yasunobu , Kondo Yoko , de Noya Belkisyole Alarcon , Noya Oscar , Kojima Somei , Kuramochi Toshiaki , Maruyama Haruhiko
Published: May 2020

Background

The cryptic parasiteSparganum proliferumproliferates in humans and invades tissues and organs. Only scattered cases have been reported, butS. proliferuminfection is always fatal. However, theS. proliferumphylogeny and lifecycle are still an enigma.

Results

To investigate the phylogenetic relationships betweenS. proliferumand other cestode species, and to examine the underlying mechanisms of pathogenicity, we sequenced the entireS. proliferumgenome. Additionally,S. proliferumplerocercoid larvae transcriptome analyses were performed to identify genes involved in asexual reproduction in the host. The genome sequences confirmed that theS. proliferumgenetic sequence is distinct from that of the closely relatedSpirometra erinaceieuropaei. Moreover, nonordinal extracellular matrix coordination allows for asexual reproduction in the host and loss of sexual maturity inS. proliferumis related to its fatal pathogenicity in humans.

Conclusions

The high-quality reference genome sequences generated should prove valuable for future studies of pseudophyllidean tapeworm biology and parasitism.
Dopamine responses reveal efficient coding of cognitive variables
Authors: Motiwala Asma , Soares Sofia , Atallah Bassam V. , Paton Joseph J. , Machens Christian K.
Published: May 2020

Reward expectations based on internal knowledge of the external environment are a core component of adaptive behavior. However, internal knowledge may be inaccurate or incomplete due to errors in sensory measurements. Some features of the environment may also be encoded inaccurately to minimise representational costs associated with their processing. We investigate how reward expectations are affected by differences in internal representations by studying rodents’ behaviour and dopaminergic activity while they make time based decisions. Several possible representations allow a reinforcement learning agent to model animals’ choices during the task. However, only a small subset of highly compressed representations simultaneously reproduce, both, animals’ behaviour and dopaminergic activity. Strikingly, these representations predict an unusual distribution of response times that closely matches animals’ behaviour. These results can inform how constraints of representational efficiency may be expressed in encoding representations of dynamic cognitive variables used for reward based computations.
Focal cortical surface cooling is a novel and safe method for intraoperative functional brain mapping
Authors: Ibayashi Kenji , Cardenas Araceli R. , Oya Hiroyuki , Kawasaki Hiroto , Kovach Christopher K. , Howard Matthew A. , Long Michael A. , Greenlee Jeremy D.W.
Published: May 2020

Objective

Electrical cortical stimulation (ECS) has been the gold standard for intraoperative functional mapping in neurosurgery, yet it carries the risk of induced seizures. Here we assess the safety of focal cortical cooling (CC) as a potential alternative to ECS for functional brain mapping.

Methods

We retrospectively reviewed 40 consecutive subjects (n=13 tumor, 27 mesial temporal lobe epilepsy (MTLE) resection) who underwent intraoperative CC during craniotomy at the University of Iowa Hospital and Clinics from 2007 through 2019 (CC group). Thirty-eight of the 40 subjects had ECS performed along with CC during the same procedure. To assess the safety of CC, intra- and post-operative seizure incidence and post-operative neurological deficits were collected together with new post-operative radiographic findings not related to the surgical procedure itself (i.e. non-mapping portions). As a control cohort, we collected 55 consecutive subjects (n=21 MTLE, 34 tumor/vascular pathology) who underwent awake ECS mapping without CC between 2006 and 2019 (ECS-alone group). To evaluate potential long term effects of mapping techniques (CC and/or ECS), we separately collected another 25 consecutive subjects who underwent anterior temporal lobectomy(ATL) without CC nor ECS between 2007 and 2019 (No ECS/No CC-ATL group).

Results

A total of 79 brain sites were cooled in the 40 CC subjects, including inferior frontal gyrus (44%), precentral gyrus (39%), postcentral gyrus (6%), subcentral gyrus (4%) and superior temporal gyrus (6%). No intraoperative seizures were reported in the CC group, whereas 3.6% of ECS-alone group had intraoperative seizures. The incidence of seizure(s) within the first post-operative week did not significantly differ amongst CC (7.9%), ECS-alone (9.0%) and No ECS/No CC-ATL groups (12%). There was no significante difference in the incidence of postoperative radiographic change between CC (7.5%) and ECS-alone groups (5.5 %). The long term seizure outcome for MTLE subjects did not statistically differ regarding ‘good’ outcomes (Engel I+II): CC group (80%), ECS-alone (83.3%) and No ECS/No CC-ATL group (83.3%).

Conclusions

Cortical cooling when used as an intraoperative mapping technique is safe, and may complement traditional electrical cortical stimulation.
The hippocampus as the switchboard between perception and memory
Authors: Treder Matthias S. , Charest Ian , Michelmann Sebastian , Martín-Buro María Carmen , Roux Frédéric , Carceller-Benito Fernando , Ugalde-Canitrot Arturo , Rollings David T. , Sawlani Vijay , Chelvarajah Ramesh , Wimber Maria , Hanslmayr Simon , Staresina Bernhard P.
Published: May 2020

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal-cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial Electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (60-110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8-12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue towards mnemonic target representations. In parallel, source-localised EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal-cortical dynamics supporting the recall process.

Significance

How do we adaptively switch from perceiving the external world to retrieving goal-relevant internal memories? To tackle this question, we used – in a cued-recall paradigm - direct intracranial recordings from the human hippocampus complemented by high-density scalp Electroencephalography (EEG). We found that a hippocampal signal ~500 ms after a perceptual cue marks the conversion from external (perceptual) to internal (mnemonic) representations. This sets in motion a recall cascade involving posterior parietal and medial prefrontal cortex, revealed via source-localised and time-resolved EEG alpha power. Together, these results unveil the hippocampal-cortical dynamics supporting rapid and flexible memory recall.
Diffusion tensor imaging and arterial tissue: establishing the influence of arterial tissue microstructure on fractional anisotropy, mean diffusivity and tractography
Authors: Tornifoglio B. , Stone A. J. , Johnston R. D. , Shahid S. S. , Kerskens C. , Lally C.
Published: May 2020

In this study we investigated the potential of diffusion tensor imaging (DTI) for providing insight into microstructural changes in arterial tissue by exploring the influence that cell, collagen and elastin content have on fractional anisotropy (FA), mean diffusivity (MD) and tractography. Five ex vivo porcine carotid artery models (n = 6 vessels each) – native, fixed native, collagen degraded, elastin degraded and decellularised – were developed to selectively remove components of arterial microstructure. Intact vessels were imaged at 7 T using a DTI protocol with b = 0 and 800 s/mm2and 10 isotopically distributed directions. FA and MD values were evaluated in the medial layer of vessels and compared across tissue models. FA values measured in native and fixed native vessels were significantly higher (p<0.0001) than those in the elastin degraded and decellularised arteries. Collagen degraded vessels had a significantly higher (p<0.01) FA than elastin degraded and decellularised vessels. Native and fixed vessels had significantly lower (p<0.0001) MD values than elastin degraded, while the MD in decellularised arteries was significantly higher than that in both native (p<0.01) and fixed (p<0.005) tissue. Significantly lower (p<0.005) MD was measured in collagen degraded compared with the elastin degraded model. Tractography results yielded similar helically arranged tracts for native and collagen degraded vessels, whilst elastin degraded and decellularised vessels showed no consistent tracts. FA, MD and tractography were found to be highly sensitive to changes in the microstructural composition of arterial tissue, with cell content being a dominant source of the measured anisotropy in the vessel wall.
Massively multiplex single-molecule oligonucleosome footprinting
Authors: Abdulhay Nour J , McNally Colin P , Hsieh Laura J , Kasinathan Sivakanthan , Keith Aidan , Estes Laurel S , Karimzadeh Mehran , Underwood Jason G , Goodarzi Hani , Narlikar Geeta J , Ramani Vijay
Published: May 2020

Our understanding of the beads-on-a-string arrangement of nucleosomes has been built largely on high-resolution sequence-agnostic imaging methods and sequence-resolved bulk biochemical techniques. To bridge the divide between these approaches, we present the single-molecule adenine methylated oligonucleosome sequencing assay (SAMOSA). SAMOSA is a high-throughput single-molecule sequencing method that combines adenine methyltransferase footprinting and single-molecule real-time DNA sequencing to natively and nondestructively measure nucleosome positions on individual chromatin fibres. SAMOSA data allows unbiased classification of single-molecular ‘states’ of nucleosome occupancy on individual chromatin fibres. We leverage this to estimate nucleosome regularity and spacing on single chromatin fibres genome-wide, at predicted transcription factor binding motifs, and across both active and silent human epigenomic domains. Our analyses suggest that chromatin is comprised of a diverse array of both regular and irregular single-molecular oligonucleosome patterns that differ subtly in their relative abundance across epigenomic domains. This irregularity is particularly striking in constitutive heterochromatin, which has typically been viewed as a conformationally static entity. Our proof-of-concept study provides a powerful new methodology for studying nucleosome organization at a previously intractable resolution, and offers up new avenues for modeling and visualizing higher-order chromatin structure.

1-sentence summary

High-throughput single-molecule real-time footprinting of chromatin arrays reveals heterogeneous patterns of oligonucleosome occupancy.
Real-time detection of bursts in neuronal cultures using a Neuromorphic Auditory Sensor and Spiking Neural Networks
Authors: Dominguez-Morales Juan P. , Buccelli Stefano , Gutierrez-Galan Daniel , Colombi Ilaria , Jimenez-Fernandez Angel , Chiappalone Michela
Published: May 2020

The correct identification of burst events is crucial in many scenarios, ranging from basic neuroscience to biomedical applications. However, none of the burst detection methods that can be found in the literature have been widely adopted for this task. As an alternative to conventional techniques, a novel neuromorphic approach for real-time burst detection is proposed and tested on acquisitions from in vitro cultures. The system consists of a Neuromorphic Auditory Sensor, which converts the input signal obtained from electrophysiological recordings into spikes and decomposes them into different frequency bands. The output of the sensor is sent to a trained spiking neural network implemented on a SpiNNaker board that discerns between bursting and non-bursting activity. This data-driven approach was compared with 8 different conventional spike-based methods, addressing some of their drawbacks, such as being able to detect both high and low frequency events and working in an online manner. Similar results in terms of number of detected events, mean burst duration and correlation as current state-of-the-art approaches were obtained with the proposed system, also benefiting from its lower power consumption and computational latency. Therefore, our neuromorphic-based burst detection paves the road to future implementations for neuroprosthetic applications.
Substitutional landscape of a split fluorescent protein fragment using high-density peptide microarrays
Authors: Antonescu Oana N. , Rasmussen Andreas , Damm Nicole A.M. , Heidemann Ditte F. , Popov Roman , Nesterov-Mueller Alexander , Johansson Kristoffer E. , Winther Jakob R.
Published: May 2020

Split fluorescent proteins have wide applicability as biosensors for protein-protein interactions, genetically encoded tags for protein detection and localization, as well as fusion partners in super-resolution microscopy. We have established and validated a novel platform for functional analysis of leave-one-out split fluorescent proteins (LOO-FPs) in high throughput and with rapid turnover. We have screened more than 12,000 strand 10 variants using high-density peptide microarrays for binding and functional complementation in Green Fluorescent Protein. We studied the effect of peptide length and the effect of different linkers to the solid support and mapped the effect of all possible amino acid substitutions on each position as well as in the context of some single and double amino acid substitutions. As all peptides were tested in 12 duplicates, the analysis rests on a firm statistical basis allowing determination of robustness and precision of the method. We showed that the microarray fluorescence correlated with the affinity in solution between the LOO-FP and peptides. A double substitution yielded a peptide with 9-fold higher affinity than the starting peptide.
Influence of fatigue on reaction times and corticospinal excitability during movement preparation
Authors: De Doncker William , Brown Katlyn E , Kuppuswamy Annapoorna
Published: May 2020

Slower self-selected ballistic movement speeds and reduced corticospinal excitability at rest are associated with post-stroke fatigue (PSF). It is unclear if fatigue-related differences in corticospinal excitability, measured using transcranial magnetic stimulation, prior to a movement will explain slower movement speeds. We hypothesized that the levels of PSF explains the modulation of corticospinal excitability during movement preparation and altered behaviour. In this study, 73 non-depressed, high functioning, chronic, first-time stroke survivors performed a simple warned and unwarned auditory reaction time task. We show a reduced suppression of corticospinal excitability during movement preparation, an increased facilitation immediately prior to movement onset and slower reaction times in those with greater levels of PSF. Reduced suppression and increased facilitation of corticospinal excitability prior to movement onset in high fatigue is an indicator of poor modulation of pre-movement excitability which may in turn reflect poor sensory processing, supporting the sensory attenuation model of fatigue.
Harnessing Tactile Waves to Measure Skin-to-Skin Interactions
Authors: Kirsch Louise P. , Job Xavier E. , Auvray Malika , Hayward Vincent
Published: May 2020

Skin-to-skin touch is an essential form of tactile interaction, yet, there is no known method to quantify how we touch our own skin or someone else’s skin. Skin-to-skin touch is particularly challenging to measure objectively since interposing an instrumented sheet, no matter how thin and flexible, between the interacting skins is not an option. To fill this gap, we explored a technique that takes advantage of the propagation of vibrations from the locus of touch to pick up a signal remotely that contains information about skin-to-skin tactile interactions. These “tactile waves” were measured by an accelerometer sensor placed on the touching finger. Tactile tonicity and speed had a direct influence on measured signal power when the target of touch was the self or another person. The measurements were insensitive to changes in the location of the sensor relative to the target. Our study suggests that this method has potential for probing behaviour during skin-to-skin tactile interactions and could be a valuable technique to study social touch, self-touch, and motor-control. The method is non-invasive, easy to commission, inexpensive, and robust.
Development and optimization of a high-throughput 3D rat Purkinje neuron culture
Authors: Uggerud Ida M. , Krakenes Torbjorn , Hirai Hirokazu , Vedeler Christian A. , Schubert Manja
Published: May 2020

Improved understanding of the mechanisms involved in neurodegenerative disease has been hampered by the lack of robust cellular models that faithfully replicatein vivofeatures. Here, we present a refined protocol for generating age-dependent, well-developed and synaptically active rat Purkinje neurons, responsive to paracrine factors and supporting a 3D cell network. Our model provides high experimental flexibility, high-throughput screening capabilities and reliability to elucidate Purkinje neuron function, communication and neurodegenerative mechanisms.
Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1
Authors: Shi Pengbo , Li Zhaosu , Xu Xing , Nie Jiaxun , Liu Dekang , Cai Qinglong , Zhao Yonghua , Guan Yun , Ge Feifei , Guan Xiaowei
Published: May 2020

Methamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.