S1 Activity Research Articles

Distinct brain-wide presynaptic networks underlie the functional identity of individual cortical neurons.

Neuronal connections provide the scaffolding for neuronal function. Revealing the connectivity of functionally identified individual neurons is necessary to understand how activity patterns emerge and support behavior. Yet, the brain-wide presynaptic wiring rules that lay the foundation for the functional selectivity of individual neurons remain largely unexplored. Cortical neurons, even in primary sensory cortex, are heterogeneous in their selectivity, not only to sensory stimuli but also to multiple aspects of behavior. Here, to investigate presynaptic connectivity rules underlying the selectivity of pyramidal neurons to behavioral state 1-12 in primary somatosensory cortex (S1), we used two-photon calcium imaging, neuropharmacology, single-cell based monosynaptic input tracing, and optogenetics. We show that behavioral state-dependent neuronal activity patterns are stable over time. These are minimally affected by neuromodulatory inputs and are instead driven by glutamatergic inputs. Analysis of brain-wide presynaptic networks of individual neurons with distinct behavioral state-dependent activity profiles revealed characteristic patterns of anatomical input. While both behavioral state-related and unrelated neurons had a similar pattern of local inputs within S1, their long-range glutamatergic inputs differed. Individual cortical neurons, irrespective of their functional properties, received converging inputs from the main S1-projecting areas. Yet, neurons that tracked behavioral state received a smaller proportion of motor cortical inputs and a larger proportion of thalamic inputs. Optogenetic suppression of thalamic inputs reduced behavioral state-dependent activity in S1, but this activity was not externally driven. Our results revealed distinct long-range glutamatergic inputs as a substrate for preconfigured network dynamics associated with behavioral state.

Effects of selenomethionine on the growth, oxidative potential, digestive enzyme activity, and immune status of juvenile sterlet (Acipenser ruthenus)

Abstract In a 56-day experiment, the effects of selenium-enriched yeast (SeY) on the growth, enzymatic activity of the gastrointestinal tract, oxidative stress parameters, and selected immunological parameters of sterlet, Acipenser ruthenus (L.), were analyzed. The concentration of selenomethionine (SeMet) from SeY in the feed was 0 mg kg−1 (C), 0.7 mg kg−1 feed (S1), 1.4 mg kg−1 feed (S2), and 2.1 mg kg−1 feed (S3). Statistically significant differences were found in the final fish body weight between the control and groups S1 and S3. A significant increase in lipase activity was found in the initial section of the small intestine of fish from group S3. The highest activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase was recorded in the liver of fish from group S2. Analyses of non-specific humoral response parameters showed an increase in ceruloplasmin activity in group S1. The lowest active dose of SeMet derived from yeast tested in this study that stimulated humoral immunity and fish growth was 0.7 mg kg−1 feed (S1).

Spiking networks that efficiently process dynamic sensory features explain receptor information mixing in somatosensory cortex.

How do biological neural systems efficiently encode, transform and propagate information between the sensory periphery and the sensory cortex about sensory features evolving at different time scales? Are these computations efficient in normative information processing terms? While previous work has suggested that biologically plausible models of of such neural information processing may be implemented efficiently within a single processing layer, how such computations extend across several processing layers is less clear. Here, we model propagation of multiple time-varying sensory features across a sensory pathway, by extending the theory of efficient coding with spikes to efficient encoding, transformation and transmission of sensory signals. These computations are optimally realized by a multilayer spiking network with feedforward networks of spiking neurons (receptor layer) and recurrent excitatory-inhibitory networks of generalized leaky integrate-and-fire neurons (recurrent layers). Our model efficiently realizes a broad class of feature transformations, including positive and negative interaction across features, through specific and biologically plausible structures of feedforward connectivity. We find that mixing of sensory features in the activity of single neurons is beneficial because it lowers the metabolic cost at the network level. We apply the model to the somatosensory pathway by constraining it with parameters measured empirically and include in its last node, analogous to the primary somatosensory cortex (S1), two types of inhibitory neurons: parvalbumin-positive neurons realizing lateral inhibition, and somatostatin-positive neurons realizing winner-take-all inhibition. By implementing a negative interaction across stimulus features, this model captures several intriguing empirical observations from the somatosensory system of the mouse, including a decrease of sustained responses from subcortical networks to S1, a non-linear effect of the knock-out of receptor neuron types on the activity in S1, and amplification of weak signals from sensory neurons across the pathway.

CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials

Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. Here we evaluated cibisatamab for advanced CEA-positive solid tumours in two open-label Phase 1 dose-escalation and -expansion studies: as a single agent with or without obinutuzumab in S1 (NCT02324257) and with atezolizumab in S2 (NCT02650713). Primary endpoints were safety, dose finding, and pharmacokinetics in S1; safety and dose finding in S2. Secondary endpoints were anti-tumour activity (including overall response rate, ORR) and pharmacodynamics in S1; anti-tumour activity, pharmacodynamics and pharmacokinetics in S2. S1 and S2 enrolled a total of 149 and 228 patients, respectively. Grade ≥3 cibisatamab-related adverse events occurred in 36% of S1 and 49% of S2 patients. The ORR was 4% in S1 and 7% in S2. In S2, patients with microsatellite stable colorectal carcinoma (MSS-CRC) given flat doses of cibisatamab and atezolizumab demonstrated an ORR of 14%. In S1 and S2, 40% and 52% of patients, respectively, developed persistent anti-drug antibodies (ADAs). ADA appearance could be mitigated by obinutuzumab-pretreatment, with 8% of patients having persistent ADAs. Overall, cibisatamab warrants further exploration in immunotherapy combination strategies for MSS-CRC.

Representation of internal speech by single neurons in human supramarginal gyrus

Speech brain–machine interfaces (BMIs) translate brain signals into words or audio outputs, enabling communication for people having lost their speech abilities due to diseases or injury. While important advances in vocalized, attempted and mimed speech decoding have been achieved, results for internal speech decoding are sparse and have yet to achieve high functionality. Notably, it is still unclear from which brain areas internal speech can be decoded. Here two participants with tetraplegia with implanted microelectrode arrays located in the supramarginal gyrus (SMG) and primary somatosensory cortex (S1) performed internal and vocalized speech of six words and two pseudowords. In both participants, we found significant neural representation of internal and vocalized speech, at the single neuron and population level in the SMG. From recorded population activity in the SMG, the internally spoken and vocalized words were significantly decodable. In an offline analysis, we achieved average decoding accuracies of 55% and 24% for each participant, respectively (chance level 12.5%), and during an online internal speech BMI task, we averaged 79% and 23% accuracy, respectively. Evidence of shared neural representations between internal speech, word reading and vocalized speech processes was found in participant 1. SMG represented words as well as pseudowords, providing evidence for phonetic encoding. Furthermore, our decoder achieved high classification with multiple internal speech strategies (auditory imagination/visual imagination). Activity in S1 was modulated by vocalized but not internal speech in both participants, suggesting no articulator movements of the vocal tract occurred during internal speech production. This work represents a proof-of-concept for a high-performance internal speech BMI.

Tactile processing in mouse cortex depends on action context

The brain receives constant tactile input, but only a subset guides ongoing behavior. Actions associated with tactile stimuli thus endow them with behavioral relevance. It remains unclear how the relevance of tactile stimuli affects processing in the somatosensory (S1) cortex. We developed a cross-modal selection task in which head-fixed mice switched between responding to tactile stimuli in the presence of visual distractors or to visual stimuli in the presence of tactile distractors using licking movements to the left or right side in different blocks of trials. S1 spiking encoded tactile stimuli, licking actions, and direction of licking in response to tactile but not visual stimuli. Bidirectional optogenetic manipulations showed that sensory-motor activity in S1 guided behavior when touch but not vision was relevant. Our results show that S1 activity and its impact on behavior depend on the actions associated with a tactile stimulus.

Enzyme activities and volatile flavor compound compositions of tiger nut paste prepared using different fungal starter strains

Abstract In order to clarify effects of different fungal strains on fermented tiger nut paste enzyme activities and volatile flavor compounds composition, koji enzyme activities and volatile flavor substances of six tiger nut paste preparations (S1–S6) were compared. The results revealed that koji enzyme activities of S4, S5 and S6 were significantly higher than corresponding activities of S1, S2 and S3. Among them, S4 exhibited the highest enzyme activity levels for cellulase, xylanase, acid protease, glucosidase, and amylase. GC-MS analysis of the six paste preparations detected 43 volatile components, including 17 aldehydes, 8 alkenes, 4 heterocyclics, 2 ketones, 2 phenols and 7 other types of compounds. Notably, S4 had the most volatile compounds (28), including 5 volatile compounds which were not detected in the other tiger nut pastes. Results of principal component analysis and partial least squares discriminant analysis (PLS-DA) revealed differences in levels of 17 volatile flavor substances among the six tiger nut paste preparations. Notably, PLS-DA results achieved more significant separation and stronger clustering trends when used to discriminate among volatile flavor substances of paste preparations fermented using single-strain starters (S1, S2, S3) versus double-strain starters (S4, S5, S6) consisting of Aspergillus oryzae, Aspergillus niger and/or Mucor. The tiger nut paste (S4) prepared by mixed fermentation of A. oryzae and A. niger had a unique flavor, producing the highest enzyme activity and a wider variety of volatile flavor compounds. Therefore, the production of tiger nut paste through compound strain koji fermentation was a feasible strategy.

Combined Experiments with in Vivo Fiber Photometry and Behavior Tests Can Facilitate the Measurement of Neuronal Activity in the Primary Somatosensory Cortex and Hyperalgesia in an Inflammatory Pain Mice Model.

The pain matrix, which includes several brain regions that respond to pain sensation, contribute to the development of chronic pain. Thus, it is essential to understand the mechanism of causing chronic pain in the pain matrix such as anterior cingulate (ACC), or primary somatosensory (S1) cortex. Recently, combined experiment with the behavior tests and in vivo calcium imaging using fiber photometry revealed the interaction between the neuronal function in deep brain regions of the pain matrix including ACC and the phenotype of chronic pain. However, it remains unclear whether this combined experiment can identify the interaction between neuronal activity in S1, which receive pain sensation, and pain behaviors such as hyperalgesia or allodynia. In this study, to examine whether the interaction between change of neuronal activity in S1 and hyperalgesia in hind paw before and after causing inflammatory pain was detected from same animal, the combined experiment of in vivo fiber photometry system and von Frey hairs test was applied. This combined experiment detected that amplitude of calcium responses in S1 neurons increased and the mechanical threshold of hind paw decreased from same animals which have an inflammatory pain. Moreover, we found that the values between amplitude of calcium responses and mechanical thresholds were shifted to negative correlation after causing inflammatory pain. Thus, the combined experiment with fiber photometry and the behavior tests has a possibility that can simultaneously consider the interaction between neuronal activity in pain matrix and pain induced behaviors and the effects of analgesics or pain treatments.

Cerebral Changes Following Carpal Tunnel Syndrome Treated with Guided Plasticity: A Prospective, Randomized, Placebo-Controlled Study.

Background Compression neuropathy, such as carpal tunnel syndrome (CTS), results in changed afferent nerve signaling, which may result in changes in somatosensory brain areas. The purpose of this study was to assess cerebral changes following unilateral CTS and to assess short-term and long-term cerebral effects of guided plasticity treatment using ipsilateral cutaneous forearm deafferentation. Methods Twenty-four patients with mild-to-moderate unilateral CTS were randomized to treatment with anesthetic cream (EMLA) or placebo. Patient-rated outcomes were assessed using Boston CTS questionnaire and disability of arm, shoulder, and hand questionnaire (QuickDASH). Patients were assessed for tactile discrimination and dexterity. Cortical activation during sensory stimulation was evaluated with functional magnetic resonance imaging at 3T. Assessments were performed at baseline, 90 minutes, and 8 weeks after treatment. Results Functional magnetic resonance imaging showed that sensory stimulation of the hand with CTS resulted in significantly less cortical activation in the primary somatosensory cortex (S1) than stimulation of the healthy hand. Treatment with cutaneous forearm deafferentation on the side with CTS resulted in increased cortical activation in S1 both after the initial treatment and following 8 weeks of treatment. In addition, QuickDASH and tactile discrimination showed improvement in the EMLA group over time. Conclusions Stimulation of median nerve-innervated fingers in patients with unilateral CTS results in smaller-than-normal activation in the contralateral S1. Cutaneous forearm anesthesia on the side with CTS results in larger activation in S1, suggesting recruitment of more neurons, and a slight improvement in sensory function.

A novel black poplar propolis extract with promising health-promoting properties: focus on its chemical composition, antioxidant, anti-inflammatory, and anti-genotoxic activities.

Propolis is a resinous mixture produced by honeybees which has been used since ancient times for its useful properties. However, its chemical composition and bioactivity may vary, depending on the geographical area of origin and the type of tree bees use for collecting pollen. In this context, this research aimed to investigate the total phenolic content (using the Folin-Ciocalteu assay) and the total antioxidant capacity (using the FRAP, DPPH, and ABTS assays) of three black poplar (Populus nigra L.) propolis (BPP) solutions (S1, S2, and S3), as well as the chemical composition (HPLC-ESI-MSn) and biological activities (effect on cell viability, genotoxic/antigenotoxic properties, and anti-inflammatory activity, and effect on ROS production) of the one which showed the highest antioxidant activity (S1). The hydroalcoholic BPP solution S1 was a prototype of an innovative, research-type product by an Italian nutraceutical manufacturer. In contrast, hydroalcoholic BPP solutions S2 and S3 were conventional products purchased from local pharmacy stores. For the three extracts, 50 phenolic compounds, encompassing phenolic acids and flavonoids, were identified. In summary, the results showed an interesting chemical profile and the remarkable antioxidant, antigenotoxic, anti-inflammatory and ROS-modulating activities of the innovative BPP extract S1, paving the way for future research. In vivo investigations will be a possible line to take, which may help corroborate the hypothesis of the potential health benefits of this product, and even stimulate further ameliorations of the new prototype.

The benefit of a double ventricular extra stimuli protocol to improve functional substrate mapping during ablation of ventricular tachycardia. - The S3-VT-FREE project

Abstract Introduction Ablation of ventricular tachycardia (VT) based on substrate-based mapping has been proposed to itemize areas of interest identifying areas of low-voltage, late potentials (LPs), and deceleration zones (DZs). However, partial delineation of targets for ablation is likely responsible for a suboptimal long-term success rate. The abnormal electrograms (EGMs), featuring low-voltage near-field components may be hidden within the high-amplitude far-field signal. We hypothesized that the acquisition of functional mapping after double ventricular extrastimuli (S3 protocol) would uncover relevant areas of functional substrate that could be missed during sinus or S1 map. We aim to evaluate the potential benefit and the feasibility of functional substrate mapping using an S3 protocol for VT ablation and to assess its colocalization with detected corridors using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). Methods We included consecutively 29 patients with structural cardiomypathy who underwent a VT ablation. The S3 protocol included: (1) assessment of the ventricular effective refractory period (ERP), (2) pacing protocol from the apex of the right ventricle with S1 x 6 (cycle length: 600ms) followed by S2 (ERP+30ms) and S3 (ERP+50ms). Electroanatomical mapping was acquired with the EnsiteX system (Abbott, IL) using HD Grid catheter and omnipolar signals. ILAMs were used to identify deceleration zones and areas of late potentials were identified for all maps. A non-invasive substrate assessment was done with LGE-MRI and post-processing with a commercially available system (ADAS3D, Spain) with automated identification of corridors. Results The S3 protocol was completed in 25 of the 29 procedures (86.2%). The repeated induction of ventricular arrhythmias did not allow for full protocol of the S3 protocol in 4 patients (13.8%). The functional substrate identified during the S3 activation mapping was significantly more extensive than the one identified using S1 and S2 activation mappings (p<0.05) (Table). The S3 protocol unmasked a higher number of DZs (p<0.01), a wider area of LPs (p<0.01), and a longer duration of the DZs (p=0.01). All DZ maps were compared with preprocedural cardiac magnetic resonance. The number of DZs matching with conduction corridors identified by LGE-MRI was higher in the activation mapping of S3 compared with the S1 and S2 ones (p=0.02). After VT ablation based on an S3 protocol, 88% of patients have been VT free during a median follow-up of 9 months. Conclusions This novel substrate-based protocol to assess the ventricular functional substrate is feasible in the majority of patients (86.2%) and allows for a better identification of targets for ablation and could facilitate VT ablation, and improve the prognosis of the patients after ablation.

Cortical Activation During Single-Legged Stance in Patients With Chronic Ankle Instability.

Chronic ankle instability (CAI) has been considered a neurophysiological condition, with dysfunctional somatosensory and motor system excitability. However, few researchers have explored the changes in cortical activation during balance tasks of patients with CAI. To compare the cortical activity during single-legged stance among CAI, copers, and uninjured control participants and to compare dynamic balance across groups. Cross-sectional study. Biomechanics laboratory. A total of 22 participants with CAI (median [interquartile range]; age = 34.5 [11.0] years, height = 170.0 [15.8] cm, mass = 67.0 [16.2] kg), 17 copers (age = 27.0 [14.0] years, height = 170.0 [9.5] cm, mass = 66.5 [16.5] kg), and 21 uninjured control participants (age = 25.0 [10.5] years, height = 170.0 [11.0] cm, mass = 64.0 [16.5] kg). Participants performed single-legged stance while cortical activation was tested with functional near-infrared spectroscopy. The peak oxyhemoglobin response of the activated cortex was calculated and compared across groups. The Y-Balance test outcomes and patient-reported outcomes were assessed and compared across groups. The CAI group had worse Y-balance test and patient-reported outcomes than the coper and uninjured control groups. Differences in the peak oxyhemoglobin response were observed for the primary somatosensory cortex (S1; F2,57 = 4.347, P = .017, ηp2 = 0.132) and superior temporal gyrus (STG; F2,57 = 4.548, P = .015, ηp2 = 0.138). Specifically, copers demonstrated greater activation in S1 and STG than the CAI (d = 0.73, P = .034, and d = 0.69, P = .043, respectively) and uninjured control (d = 0.77, P = .036, and d = 0.88, P = .022, respectively) groups. No differences were found in the cortical activation between CAI and uninjured control participants. Copers displayed greater cortical activation in S1 and STG than CAI and uninjured control participants. Greater activation in S1 and STG suggested a better ability to perceive somatosensory stimuli and may represent a compensatory mechanism that allows copers to maintain good functional ability after the initial severe ankle sprain.

Antimicrobial Activity and Molecular Docking Studies of the Biotransformation of Diterpene Acanthoic Acid Using the Fungus Xylaria sp.

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3β,7β-dihydroxyacanthoic acid (S1). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1.

Augmented pain-evoked primary sensorimotor cortex activation in adolescent girls with juvenile fibromyalgia.

Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM. Thirty-three adolescent girls with JFM and 33 healthy adolescent girls underwent functional magnetic resonance imaging scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm 2 and rated pain intensity and unpleasantness on a computerized Visual Analogue Scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses. The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities ( P < 0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm 2 (Z > 3.1, cluster-corrected P < 0.05), and the peak S1 activation magnitudes significantly correlated with the scores on the Widespread Pain Index ( r = 0.35, P = 0.048) with higher activation associated with more widespread pain. We also found that greater primary sensorimotor cortex activation in response to 4 kg/cm 2 mediated the between-group differences in pain intensity ratings ( P < 0.001). In conclusion, we found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input.

Human orbitofrontal cortex signals decision outcomes to sensory cortex during behavioral adaptations

The ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). However, how the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-selective S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implement computations critical for adaptive behavior.

Content representation of tactile mental imagery in primary somatosensory cortex.

The imagination of tactile stimulation has been shown to activate primary somatosensory cortex (SI) with a somatotopic specificity akin to that seen during the perception of tactile stimuli. Using fMRI and MVPA, we investigate if this recruitment of sensory regions also reflects content-specific activation, i.e. whether the activation in SI is specific to the mental content participants imagined. To this end, healthy volunteers (n=21) either perceived or imagined three types of vibrotactile stimuli (mental content) while fMRI data was acquired. Independent of the content, during tactile mental imagery we found activation of fronto-parietal regions, supplemented with activation in the contralateral BA2 subregion of SI, replicating previous reports. While the imagery of the three different stimuli did not reveal univariate activation differences, using multivariate pattern classification we were able to decode the imagined stimulus type from BA2. Moreover, cross-classification revealed that tactile imagery elicits activation patterns similar to those evoked by the perception of the respective stimuli. These findings promote that mental tactile imagery involves the recruitment of content-specific activation patterns in sensory cortices, namely in SI.Significance StatementIt has been shown previously that mental imagery of sensations in different modalities can activate respective primary sensory cortices (visual/auditory/tactile). However, a relation of such activation to the imagined mental content was mainly shown for the visual system. Here, we generalize this concept to the somatosensory domain by showing that content-specific activation during tactile mental imagery can be found in primary somatosensory cortex subarea BA2. Most importantly, we show that tactile imagery elicits activation patterns similar to those evoked by sensory stimulation. Our results provide further evidence that sensory recruitment is among the brain processes that allow conscious information representation.

Neuropathic pain following spinal cord hemisection induced by the reorganization in primary somatosensory cortex and regulated by neuronal activity of lateral parabrachial nucleus.

Neuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS). Through behavioral tests, we first identified mechanical allodynia and thermal hyperalgesia following LHS. We then applied two-photon microscopy to observe calcium activity in S1 during mechanical or thermal stimulation and long-term spontaneous calcium activity after LHS. By slice patch clamp recording, the electrophysiological characteristics of neurons in lPBN were explored. Finally, exploiting chemogenetic activation or inhibition of the neurons in lPBN, allodynia or hyperalgesia was regulated. The calcium activity in left S1 was increased during mechanical stimulation of right hind limb and thermal stimulation of tail, whereas in right S1 it was increased only with thermal stimulation of tail. The spontaneous calcium activity in right S1 changed more dramatically than that in left S1 after LHS. The lPBN was also activated after LHS, and exploiting chemogenetic activation or inhibition of the neurons in lPBN could induce or alleviate allodynia and hyperalgesia in central neuropathic pain. The neuronal activity changes in S1 are closely related to limb pain, which has accurate anatomical correspondence. After LHS, the spontaneously increased functional connectivity of calcium transient in left S1 is likely causing the mechanical allodynia in right hind limb and increased neuronal activity in bilateral S1 may induce thermal hyperalgesia in tail. This state of allodynia and hyperalgesia can be regulated by lPBN.

Axonal connections between S1 barrel, M1, and S2 cortex in the newborn mouse.

The development of functionally interconnected networks between primary (S1), secondary somatosensory (S2), and motor (M1) cortical areas requires coherent neuronal activity via corticocortical projections. However, the anatomical substrate of functional connections between S1 and M1 or S2 during early development remains elusive. In the present study, we used ex vivo carbocyanine dye (DiI) tracing in paraformaldehyde-fixed newborn mouse brain to investigate axonal projections of neurons in different layers of S1 barrel field (S1Bf), M1, and S2 toward the subplate (SP), a hub layer for sensory information transfer in the immature cortex. In addition, we performed extracellular recordings in neocortical slices to unravel the functional connectivity between these areas. Our experiments demonstrate that already at P0 neurons from the cortical plate (CP), layer 5/6 (L5/6), and the SP of both M1 and S2 send projections through the SP of S1Bf. Reciprocally, neurons from CP to SP of S1Bf send projections through the SP of M1 and S2. Electrophysiological recordings with multi-electrode arrays in cortical slices revealed weak, but functional synaptic connections between SP and L5/6 within and between S1 and M1. An even lower functional connectivity was observed between S1 and S2. In summary, our findings demonstrate that functional connections between SP and upper cortical layers are not confined to the same cortical area, but corticocortical connection between adjacent cortical areas exist already at the day of birth. Hereby, SP can integrate early cortical activity of M1, S1, and S2 and shape the development of sensorimotor integration at an early stage.

Amyloid Deposition and Dendritic Complexity of Corticocortical Projection Cells in Five Familial Alzheimer's Disease Mouse

In Alzheimer’s disease and related dementias, amyloid beta (Aβ) and amyloid plaques can disrupt long-term synaptic plasticity, learning and memory and cognitive function. Plaque accumulation can disrupt corticocortical circuitry leading to abnormalities in sensory, motor, and cognitive processing. In this study, using 5xFAD (five Familial Alzheimer's Disease – FAD – mutations) mice, we evaluated amyloid plaque formation in different cortical areas, and whether differential amyloid accumulation across cortical fields correlates with changes in dendritic complexity of layer 3 corticocortical projection neurons and functional responses in the primary somatosensory cortex following whisker stimulation. We focused on three cortical areas: the primary somatosensory cortex (S1), the primary motor cortex (M1), and the prefrontal cortex (PFC including the anterior cingulate, prelimbic, and infralimbic subdivisions). We found that Aβ and amyloid plaque accumulation is not uniform across 5xFAD cortical areas, while there is no expression in littermate controls. We also found that there are differential layer 3 pyramidal cell dendritic complexity changes across the three areas in 5xFAD mice, compared to same age controls, with no apparent relation to differential amyloid accumulation. We used voltage-sensitive dye imaging (VSDi) to visualize neural activity in S1, M1 and PFC following whisker activation. Control mice show normal physiological responses in all three cortical areas, whereas 5xFAD mice only display physiological responses in S1. Taken together our results show that 5xFAD mutation affects the overall dendritic morphology of layer 3 pyramidal cells across sensory-motor and association cortex irrespective of the density and distribution of the Aβ amyloid proteins. Corticocortical circuitry between the sensory and motor/association areas is most likely disrupted in 5xFAD mice as cortical responses to whisker stimulation are altered.

Perceived discomfort and neuromuscular fatigue during long-duration real driving with different car seats.

Identification of the seat features that could improve driving experience is a main issue for automotive companies. Long duration real driving sessions were performed to assess the effect of three seats (soft-S1, firm-S2 and suspended-S3) on perceived discomfort and neuromuscular fatigue (NMF). For each seat, the muscular activity of bilateral Trapezius Descendens (TD), Erector Spinae (ES) and Multifidus (MF) muscles of twenty-one participants was recorded during real driving sessions of 3-hours each lasting approximately 3 hours and following the same itinerary. During each driving session, participants were also regularly asked to self-evaluate their level of whole-body and local discomfort. In addition, an endurance static test (EST) was performed before (ESTpre) and after (ESTpost) each driving session to assess the seat effect on physical capacity. Whole-body discomfort increased with driving time for all seats, but this increase became significant latter for S3. The highest scores of local discomfort occurred for neck and lower back. Contrary to S1 and S2, the duration of ESTpost was not significantly lower compared to ESTpre with the S3. Interestingly, muscular activity of S1 remained stable throughout the driving task which could be attributed to sustained muscular contraction, while muscular recruitment adjustments occurred for S2 and S3 from 1H00 of driving. This muscular compensation concerns mostly the right side for S2 and S3 but with different profiles. On the left side, the muscular adjustments concern only the MF with S2 and the ES with S3. Overall, our results demonstrated that S3 could be considered as the most suitable seat to delay discomfort and NMF appearance.