bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging through Windansee electrode arrays reveals a small fraction of local neurons following surface MUA
Authors: Thunemann Martin , Hossain Lorraine , Ness Torbjørn V. , Rogers Nicholas , Lee Keundong , Lee Sang Heon , Kılıç Kıvılcım , Oh Hongseok , Economo Michael N. , Gilja Vikash , Einevoll Gaute T. , Dayeh Shadi A. , Devor Anna 
Published: September 2022

AbstractPrior studies have shown that neuronal spikes can be recorded with microelectrode arrays placed on the cortical surface. However, the etiology of these spikes remains unclear. Because the top cortical layer (layer 1) contains very few neuronal cell bodies, it has been proposed that these spikes originate from neurons with cell bodies in layer 2. To address this question, we combined two-photon calcium imaging with electrophysiological recordings from the cortical surface in awake mice using chronically implanted PEDOT:PSS electrode arrays on transparent parylene C substrate.Our electrode arrays (termed Windansee) were integrated with cortical windows offering see-through optical access while also providing measurements of local field potentials (LFP) and multiunit activity (MUA) from the cortical surface. To enable longitudinal data acquisition, we have developed a mechanical solution for installation, connectorization, and protection of Windansee devices aiming for an unhindered access for high numerical aperture microscope objectives and a lifetime of several months while worn by a mouse.Contrary to the common notion, our measurements revealed that only a small fraction of layer 2 neurons from the sampled pool (~13%) faithfully followed MUA recorded from the surface above the imaging field-of-view. Surprised by this result, we turned to computational modeling for an alternative explanation of the MUA signal. Using realistic modeling of neurons with back-propagating dendritic properties, we computed the extracellular action potential at the cortical surface due to firing of local cortical neurons and compared the result to that due to axonal inputs to layer 1. Assuming the literature values for the cell/axon density and firing rates, our modeling results show that surface MUA due to axonal inputs is over an order of magnitude larger than that due to firing of layer 2 pyramidal neurons.Thus, a combination of surface MUA recordings with two-photon calcium imaging can provide complementary information about the input to a cortical column and the local circuit response. Cortical layer I plays an important role in integration of a broad range of cortico-cortical, thalamocortical and neuromodulatory inputs. Therefore, detecting their activity as MUA while combining electrode recording with two-photon imaging using optically transparent surface electrode arrays would facilitate studies of the input/output relationship in cortical circuits, inform computational circuit models, and improve the accuracy of the next generation brain-machine interfaces.
Chemoenzymatic Measurement of Cell-surface Glycan in Single-cell Multiomics: LacNAc as an Example
Authors: Yu Wenhao , Zhao Xinlu , Jalloh Abubakar S. , Zhao Yingying , Dinner Brandon , Yang Yang , Ouyang Shian , Li Yachao , Tian Tian , Zhao Zihan , Yang Rong , Chen Mingkuan , Lauvau Gregoire , Guo Zijian , Wu Peng , Li Jie P. 
Published: September 2022

ABSTRACTDespite the rich information of a cell’s physiological state encoded in the dynamic changes of cell-surface glycans, methods of capturing glycosylation states at the single-cell level are quite limited. Here we report a chemoenzymatic single-cell N-acetyllactosamine (LacNAc) detection method via tagging the LacNAc with a specific DNA barcode. Compared to the lectin-based glycan detection, the chemoenzymatic labeling does not change the transcriptional status of immune cells and is more compatible with scRNA-seq. Integrated analysis of LacNAc and transcriptome of T cells at a single-cell level reveals that the quantity of cell-surface LacNAc is significantly upregulated in activated CD8+ T cells but maintained at the basal level in quiescent CD8+ T cells (i.e., naive and central memory T cells). Further analysis confirms that the LacNAc level is positively correlated to the glycolytic activity of CD8+ T cells at all statues. Taken together, our study demonstrates the feasibility of chemoenzymatic detection of cell-surface glycan in single-cell RNA sequencing-based multiomics with information of TCR sequence and cell-surface epitopes (i.e., scTCR and CITE-seq) and offers a new way to characterize the biological role of glycan in diversified physiological states.
Altered tau in rTg4510 mice after a single interfaced CHIMERA traumatic brain injury
Authors: Cheng Wai Hang , Cheung Honor , Kang Amy , Fan Jianjia , Cooper Jennifer , Anwer Mehwish , Barron Carlos , Wilkinson Anna , Hu Grace , Yue Jefferey , Cripton Peter A , Vocadlo David , Wellington Cheryl L 
Published: September 2022

AbstractTraumatic brain injury (TBI) in an established risk factor for neurodegenerative disease. In this report, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to study the effects of a single moderate-severe TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice were impacted at 4.0J at 4-mo of age using interfaced CHIMERA and compared to sham controls. Immediately after injury, moderate-severe TBI induced significant mortality (7/15; 47%), and a prolonged duration of loss of righting reflex. At 2-mo post-injury, surviving mice displayed significant histological evidence of microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting showed that TBI mice had a reduced p-GSK-3β (S9):GSK-3β ratio, suggesting greater tau kinase activity. However, tauopathy in surviving TBI mice showed a divergent response, with 3/8 mice having a very low level of tau protein in brain lysates (i.e. lower than sham), and were thus analyzed separately from the other 5/8 TBI mice that maintained the expected level of total tau. Compared to sham controls, TBI mice with normal tau levels had increased p-tau (PHF1 and AT8), increased autophagolysosome accumulation (p62 and Cathepsin D) and decreased hippocampal size. These findings were not observed in TBI mice with low total tau levels. These observations suggest that TBI leads to chronic white matter injury and altered GSK-3β activity. However, post-injury tauopathy and autophagolysosome accumulation diverged in surviving mice through mechanisms that remain to be defined.
Neural Adaptation and Fractional Dynamics as a Window to Underlying Neural Excitability
Authors: Lundstrom Brian N. , Richner Tom 
Published: September 2022

AbstractThe relationship between macroscale electrophysiological recordings and the dynamics of underlying neural activity remains unclear. We have previously shown that low frequency EEG activity (<1 Hz) is decreased at the seizure onset zone (SOZ), while higher frequency activity (1-50 Hz) is increased. These changes result in power spectral densities (PSDs) with flattened slopes near the SOZ, which are assumed to be areas of increased excitability. We wanted to understand possible mechanisms underlying PSD changes in brain regions of increased excitability. We hypothesize that these observations are consistent with changes in adaptation within the neural circuit.We developed a theoretical framework and tested the effect of adaptation mechanisms, such as spike frequency adaptation and synaptic depression, on excitability and PSDs using filter-based neural mass models and conductance-based models. We compared the contribution of single timescale adaptation and multiple timescale adaptation.We found that adaptation with multiple timescales alters the PSDs. Multiple timescales of adaptation can approximate fractional dynamics, a form of calculus related to power laws, history dependence, and non-integer order derivatives. Coupled with input changes, these dynamics changed circuit responses in unexpected ways. Increased input without synaptic depression increases broadband power. However, increased input with synaptic depression may decrease power. The effects of adaptation were most pronounced for low frequency activity (< 1Hz). Increased input combined with a loss of adaptation yielded reduced low frequency activity and increased higher frequency activity, consistent with clinical EEG observations from SOZs.Spike frequency adaptation and synaptic depression, two forms of multiple timescale adaptation, affect low frequency EEG and the slope of PSDs. These neural mechanisms may underlie changes in EEG activity near the SOZ and relate to neural hyperexcitability. Neural adaptation may be evident in macroscale electrophysiological recordings and provide a window to understanding neural circuit excitability.Author SummaryElectrophysiological recordings such as EEG from the human brain often come from many thousands of neurons or more. It can be difficult to relate recorded activity to characteristics of the underlying neurons and neural circuits. Here, we use novel theoretical framework and computational neural models to understand how neural adaptation might be evident in human EEG recordings. Neural adaptation includes mechanisms such as spike frequency adaptation and short-term depression that emphasize stimulus changes and help promote stability. Our results suggest that changes in neural adaptation affect EEG signals, especially at low frequencies. Further, adaptation can lead to changes related to fractional derivatives, a kind of calculus with non-integer orders. Neural adaptation may provide a window into understanding specific aspects of neuron excitability even from EEG recordings.
Sensory uncertainty punctuates motor learning independently of movement error when both feedforward and feedback control processes are engaged
Authors: Hewitson Christopher L. , Kaplan David M. , Crossley Matthew J. 
Published: September 2022

AbstractIntegrating sensory information during movement and adapting motor plans over successive movements are both essential for accurate, flexible motor behavior. When an ongoing movement is off target, feedback control mechanisms update the descending motor commands to counter the sensed error. Over longer timescales, errors induce adaptation in feedforward planning so that future movements become more accurate and require less online adjustment from feedback control processes. Both the degree to which sensory feedback is integrated into an ongoing movement and the degree to which movement errors drive adaptive changes in feedforward motor plans have been shown to scale inversely with sensory uncertainty. However, since they have only been studied in isolation of each other, little is know about how they respond to sensory uncertainty in real-world movement contexts where they co-occur. Here, we show that sensory uncertainty impacts feedforward adaptation of reaching movements differently when feedback integration is present versus when it is absent. In particular, participants gradually adjust their movements from trial-to-trial in a manner that is well characterised by a slow and consistent envelope of error reduction. Riding on top of this slow envelope, participants display large and abrupt changes in their initial movement vectors that clearly correlate with the degree of sensory uncertainty present on the previous trial. However, these abrupt changes are insensitive to the magnitude and direction of the sensed movement error. These results prompt important questions for current models of sensorimotor learning under uncertainty and open up exciting new avenues for future exploration.Author SummaryA large body of literature shows that sensory uncertainty inversely scales the degree of error-driven corrections made to motor plans from one trial to the next. However, by limiting sensory feedback to the endpoint of movements, these studies prevent corrections from taking place during the movement. Here, we show that when such corrections are promoted, sensory uncertainty punctuates between-trial movement corrections with abrupt changes that closely track the degree of sensory uncertainty but are insensitive to the magnitude and direction of movement error. This result marks a significant departure from existing findings and opens up new paths for future exploration.
TRPA1 analgesia is mediated by kappa opioid receptors
Authors: Semizoglou Evangelia , Gentry Clive , Vastani Nisha , Stucky Cheryl L. , Andersson David A. , Bevan Stuart 
Published: September 2022

ABSTRACTTRPA1 expressed in peripheral sensory neurons is important for nociception. Pharmacological inhibition or genetic ablation of TRPA1 profoundly reduces normal behavioural sensitivity to noxious cold and mechanical stimulation, as well as sensory neuron responses to mechanical stimulation. TRPA1 inhibition also reverses cold and mechanical hypersensitivities in chronic pain models in vivo. Here we demonstrate that these striking effects of TRPA1 inactivation result from an increased constitutive activity of kappa opioid receptors (KOR) co-expressed with TRPA1 in sensory neurons. Inhibition of KOR in Trpa1-/- mice restores nociception and neuronal activity to the levels observed in wild-type mice and reverses the analgesic effects of TRPA1 antagonism in naïve mice and in neuropathic and inflammatory pain conditions. TRPA1 regulation of KOR activity in sensory neurons provides a novel mechanism to produce peripherally mediated analgesia. Our findings suggest that TRP channel regulation of constitutive GPCR activity, may be a process of general physiological importance.
Release of lipid nanodiscs from charged nano-droplets in the electrospray ionization process revealed by microsecond atomistic molecular dynamics simulations
Authors: Wang Beibei , Tieleman D. Peter 
Published: September 2022

ABSTRACTElectrospray ionization (ESI) prevents the analyte being split into fragments and is widely used to analyze biomolecules. Nanodiscs provide a native-like environment for membrane proteins, while making them accessible in aqueous solution for analysis. We performed microsecond (μs) molecular dynamics simulations at different temperatures, to provide atomistic insight in the release of intact nanodiscs from charged nano-droplets, the late stage of the ESI process. Two distinct main scenarios, at-center and off-center, were observed. The at-center scenario follows the charged residue model, and in the process the nanodisc stays well in the droplet interior, with the membrane scaffold protein (MSP) keeping its annular geometry. As solvent evaporates, lipids turn over to protect the hydrophilic surface. The off-center scenario conforms to a hybrid model of the charged residue model and chain ejection model. The nanodisc migrates to the water/air interface, leading to lipids escaping from the dissociated dimer and the partial ejection of one monomer of MSP. A diversity of morphologies of product gaseous ions was observed, as evidenced by their structural details, collision cross sections and moments of inertia. Our results are in reasonable agreement with results of mass spectrometry in mass-to-charge ratio, charge state and collision cross section. Our work displays the first atomistic view of a heterogeneous system, a lipid nanodisc, releasing from highly charged nano-droplets into the gas phase, which may provide structural supports for the interpretation of mass spectra of complicated systems. What we observe in our simulations could also be generalized to other protein-lipid systems.
Dissociated amplitude and phase effects of alpha oscillation in a nested structure of rhythm- and sequence-based temporal expectation
Authors: Su Zhongbin , Zhou Xiaolin , Wang Lihui 
Published: September 2022

AbstractThe human brain can utilize various information to form temporal expectation and optimize perceptual performance. Here we show dissociated amplitude and phase effects of pre-stimulus alpha oscillation in a nested structure of rhythm- and sequence-based expectation. A visual stream of rhythmic stimuli was presented in a fixed sequence such that their temporal positions could be predicted by either the low-frequency rhythm, the sequence, or the combination. The behavioral modelling indicated that rhythmic and sequence information additively led to increased accumulation of sensory evidence and alleviated threshold for the perceptual discrimination of the expected stimulus. The electroencephalographical (EEG) results showed that the alpha amplitude was dominated by rhythmic information, with the amplitude fluctuating in the same frequency of the oscillation entrained by the rhythmic information (i.e., phase-amplitude coupling). The alpha phase, however, was affected by both rhythmic and sequence information. Importantly, rhythm-based expectation improved the perceptual performance by decreasing the alpha amplitude, whereas sequence-based expectation did not further decrease the amplitude on top of rhythm-based expectation. Moreover, rhythm-based and sequence-based expectation collaboratively improved the perceptual performance by biasing the alpha oscillation toward the optimal phase. Our findings suggested flexible coordination of multiscale brain oscillations in dealing with a complex environment.
Combating pancreatic cancer with ovarian cancer cells
Authors: Lin Xiao , Cui Chunmei , Cui Qinghua 
Published: September 2022

AbstractWith overall five-year survival rate less than 10%, pancreatic cancer (PC) represents the most lethal one in all human cancers. Given that the incidence of PC is still increasing and current cancer treatment strategies are often inefficacious, its therapy is still a huge challenge. Here, we first revealed ovarian serous carcinoma is mostly anti-correlated with pancreatic cancer in gene expression signatures. Based on this observation, we proposed that ovarian cancer cells could defense PC. To confirm this strategy, we first showed that ovarian cancer cell SKOV3 can significantly inhibit the proliferation of pancreatic cancer cell SW1990 when they were co-cultured. We further validated this strategy by an animal model of pancreatic cancer xenografts. The result showed that the injection of SKOV3 significantly inhibits pancreatic cancer xenografts. Moreover, we found that SKOV3 with transgenic African elephant TP53 gene further enhances the therapeutic effect. RNA-sequencing analysis revealed that the ovarian cancer cell treatment strikingly induced changes of genes being involved in pancreas function and phenotype (e.g. enhancing pancreas function, pancreas regeneration, and cell adhesion) but not immune and inflammation related functions, suggesting that the proposed strategy is different from immunotherapy and could be a novel strategy for cancer treatment.
In silicoconformational features of botulinum toxins A1 and E1 according to the intraluminal acidification
Authors: Cottone Grazia , Chiodo Letizia , Maragliano Luca , Popoff Michel-Robert , Rasetti-Escargueil Christine , Lemichez Emmanuel , Malliavin Thérèse E. 
Published: September 2022

AbstractAlthough the botulinum neurotoxins (BoNTs) are among the most toxic compounds found in nature, their molecular mechanism of action is far from being elucidated. A key event is the conformational transition due to the acidification of the interior of synaptic vesicles, and leading to the translocation of the BoNT catalytic domain into the neuronal cytosol. To investigate these conformational variations, homology modelling and atomistic simulations are combined to explore the internal dynamics of the subtypes BoNT/A1, the most-used in medical applications, and BoNT/E1, the most kinetically efficient. This first simulation study of di-chain BoNTs in closed and open states includes the effects of neutral and acidic pH. The conformational mobility is driven by domains displacements; the ganglioside binding site in the receptor binding domain, the translocation domain (HCNT) switch and the beltαhelix visit multiple conformations depending on the primary sequence and on the pH. Fluctuations of the beltαhelix are observed for closed conformations of the toxins and at acidic pH, and patches of more accessible residues appear in the same conditions in the core translocation domain HCNT. These findings suggest that during translocation, the larger mobility of belt could be transmitted to HCNT, leading to a favorable interaction of HCNTresidues with the non-polar membrane environment.Key ContributionThe molecular dynamics simulations presented here provide a structural and functional annotation of full-length BoNTs composed by two distinct protein chains. Two different conformations (open and closed) as well as two different protonation states, corresponding to acidic and neutral pH, have been considered. Results from the present work supports a model of mobility in which the individual domains fluctuate around stable conformations and the overall structure mobility arise from relative displacements of the domains.
Alpha oscillations reflect similar mapping mechanisms for localizing touch on hands and tools
Authors: Fabio Cécile , Salemme Romeo , Farnè Alessandro , Miller Luke E. 
Published: September 2022

ABSTRACTNumerous studies have suggested that tools become incorporated into a representation of our body. A prominent hypothesis suggests that our brain re-uses body-based computations when we use tools. However, little is known about how this is implemented at the neural level. Here we used the ability to localize touch on both tools and body parts as a case study to fill this gap. Neural oscillations in the alpha (8-13 Hz) and beta (15-25 Hz) frequency bands are involved in mapping touch on the body in distinct reference frames. Alpha activity reflects the mapping of touch in external coordinates, whereas beta activity reflects the mapping of touch in skin-centered coordinates. Here, we aimed at pinpointing the role of these oscillations during tool-extended sensing. We recorded participants’ oscillatory activity while tactile stimuli were applied to either hands or the tips of hand-held rods. The posture of the hands/tool-tips was uncrossed or crossed at participants’ body midline in order for us to disentangle brain responses related to different coordinate systems. We found that alpha-band activity was modulated similarly across postures when localizing touch on hands and on tools, reflecting the position of touch in external space. Source reconstruction also indicated a similar network of cortical regions involved for tools and hands. Our findings strongly suggest that the brain uses similar oscillatory mechanisms for mapping touch on the body and tools, supporting the idea of neural processes being repurposed for tool-use.SIGNIFICANCE STATEMENTTool use is one of the defining traits of humankind. Tools allow us to explore our environment and expand our sensorimotor abilities. A prominent hypothesis suggests that our brain re-uses body-based neural processing to swiftly adapt to the use of tools. However, little is known about how this is implemented at the neural level. In the present study we used the ability to map touch on both tools and body parts as a case study to fill this gap. We found that the brain uses similar oscillatory mechanisms for mapping touch on a hand-held tool and on the body. These results provide novel and compelling support to the idea that neural processes devoted to body-related information are re-purposed for tool-use.