Somatosensory Cortex Research Articles

Cortico-cortical connectivity of the somatosensory cortex of the agouti: Topographical organization and evolutionary implications.

Understanding patterns of cortico-cortical connections in both frequently and infrequently studied species advances our knowledge of cortical organization and evolution. The agouti (Dasyprocta aguti, a medium-size South American rodent) offers a unique opportunity, because of its large lissencephalic brain and its natural behaviors, such as gnawing and hiding seeds, that require bimanual interaction while sitting on its hindlimbs and aligning its head to receive images of the horizon on the retinal visual streak. There have been no previous studies of the intrinsic and extrinsic ipsilateral projections of the agouti's primary somatosensory cortical area (S1). In the present study, we utilized biotinylated dextran (BDA) anatomical tract-tracer injections combined with microelectrode electrophysiological mapping, correlated with analysis of cytochrome oxidase (CO) histochemical staining, to investigate the ipsilateral corticocortical connectivity of the agouti's S1. By injecting BDA into electrophysiologically identified regions within the S1, we revealed ipsilateral intrinsic connections, as well as connections with cortical areas rostral and caudal to S1, and homotopic labeling in the second somatosensory cortical area (S2). In addition, we identified a focal cluster of labeled axons and axonal terminals adjacent to the rhinal fissure, tentatively named the parietal rhinal area (PR). The analysis of CO reactivity allowed delineation of the boundaries and subdivisions of S1, as well as the locations and limits of primary auditory and visual areas. These findings provide support for the notion of a similar pattern of somatosensory cortical organization and connectivity across mammalian species.

Predicting proprioceptive cortical anatomy and neural coding with topographic autoencoders.

Proprioception is one of the least understood senses, yet fundamental for the control of movement. Even basic questions of how limb pose is represented in the somatosensory cortex are unclear. We developed a topographic variational autoencoder with lateral connectivity (topo-VAE) to compute a putative cortical map from a large set of natural movement data. Although not fitted to neural data, our model reproduces two sets of observations from monkey centre-out reaching: 1. The shape and velocity dependence of proprioceptive receptive fields in hand-centered coordinates despite the model having no knowledge of arm kinematics or hand coordinate systems. 2. The distribution of neuronal preferred directions (PDs) recorded from multi-electrode arrays. The model makes several testable predictions: 1. Encoding across the cortex has a blob-and-pinwheel-type geometry of PDs. 2. Few neurons will encode just a single joint. Our model provides a principled basis for understanding of sensorimotor representations, and the theoretical basis of neural manifolds, with applications to the restoration of sensory feedback in brain-computer interfaces and the control of humanoid robots.

Chronic silencing of subsets of cortical layer 5 pyramidal neurons has a long-term influence on the laminar distribution of parvalbumin interneurons and the perineuronal nets.

Neural networks are established throughout cortical development, which require the right ratios of glutamatergic and GABAergic neurons. Developmental disturbances in pyramidal neuron number and function can impede the development of GABAergic neurons, which can have long-lasting consequences on inhibitory networks. However, the role of deep-layer pyramidal neurons in instructing the development and distribution of GABAergic neurons is still unclear. To unravel the role of deep-layer pyramidal neuron activity in orchestrating the spatial and laminar distribution of parvalbumin neurons, we selectively manipulated subsets of layer 5 projection neurons. By deleting Snap25 selectively from Rbp4-Cre + pyramidal neurons, we abolished regulated vesicle release from subsets of cortical layer 5 projection neurons. Our findings revealed that chronically silencing subsets of layer 5 projection neurons did not change the number and distribution of parvalbumin neurons in the developing brain. However, it did have a long-term impact on the laminar distribution of parvalbumin neurons and their perineuronal nets in the adult primary motor and somatosensory cortices. The laminar positioning of parvalbumin neurons was altered in layer 4 of the primary somatosensory cortex in the adult Snap25 cKO mice. We discovered that the absence of layer 5 activity only had a transient effect on the soma morphology of striatal PV neurons during the third week of postnatal development. We also showed that the relationship between parvalbumin neurons and the perineuronal nets varied across different cortical layers and regions; therefore, their relationship is far more complex than previously described. The current study will help us better understand the bidirectional interaction between deep-layer pyramidal cells and GABAergic neurons, as well as the long-term impact of interrupting pyramidal neuron activity on inhibitory network formation.

Functional ultrasound and brain connectivity reveal central nervous system compromise in Trembler-J mice model of Charcot-Marie-Tooth disease

The Charcot-Marie-Tooth-1E (CMT1E) disease is typically described as a peripheral neuropathy in humans, causing decreased nerve conduction, spastic paralysis, and tremor. The Trembler-J (TrJ) mice serve as a high fidelity model of this disease. Here, we use functional ultrasound (fUS) and functional connectivity (FC) to analyze TrJ mice’s brain activity during sensory stimulation and resting state experiments against wild type (WT) mice - the healthy counterpart. fUS is an imaging technique that measures cerebral blood volume (CBV) temporal changes. We study these changes in the primary somatosensory cortex barrel field (S1BF) of both mice populations during periodic vibrissae stimulation, measuring the number of pixels that correlate to the stimulation (i.e., the size of the activation area), the average correlation of these pixels (i.e., the response strength), and the CBV’s rate of change for each stimulation (i.e., the hemodynamic response). Then, we construct a FC matrix for each genotype and experiment by correlating the CBV signals from the eight cortical regions defined by the Paxinos and Franklin atlas. Our results show that TrJ mice have significantly diminished neurovascular responses and altered brain connectivity with respect to WT mice, pointing to central nervous system effects that could shift our understanding of the CMT1E disease.

Alterations of fractional anisotropy and white matter integrity in irritable bowel syndrome: a systematic review and meta-analysis of diffusion tensor imaging studies

Background and aimThe neurological processes responsible for irritable bowel syndrome (IBS) pathophysiology and its clinical potentials are not fully understood. The current study aimed to examine white matter microstructural abnormalities and the reasons behind white matter impairment in individuals with irritable bowel syndrome by performing a meta-analysis of diffusion tensor imaging studies.MethodsPubMed, Scopus and Web of Science were searched until April 2024. Chosen articles based on our defined eligibility criteria were extracted for the data relating to fractional anisotropy and brain connectivity. Webplot digitizer was used to extract digital data. We used the latest version of STATA(ver18) to meta-analyze the data. Quality assessment of studies was done using a critical appraisal tool. Egger’s test for minor study effects assessed the publication bias.Results543 IBS cases and 472 healthy controls were included in this study. The mean age of the case and control group was 35.2 ± 17.4 and 33.6 ± 15.8 (mean ± SD), respectively. There was no statistically significant difference in age between groups (p > 0.05). Analyzed Standard mean difference using a fixed model for Fractional anisotropy of regions of interest (ROI) associated with sensory processing, such as the thalamus, insula, primary somatosensory cortex, dorsal cingulum and the fornix in selected studies showcased decreased white matter interactivity in case group however this decrease was not statistically different [SMD −88, 95%CI (−1.32, −0.44), p > 0.05].ConclusionFurther investigation is necessary to ascertain whether the modified structural connectivity mentioned in this study is a contributing factor to IBS, an outcome of the condition, a risk factor for it, or, more probably, a consequence of a mutually influential relationship between the changes observed in the white matter tract and IBS symptoms.

A connectome manipulation framework for the systematic and reproducible study of structure–function relationships through simulations

Abstract Synaptic connectivity at the neuronal level is characterized by highly non-random features. Hypotheses about their role can be developed by correlating structural metrics to functional features. But to prove causation, manipulations of connectivity would have to be studied. However, the fine-grained scale at which non-random trends are expressed makes this approach challenging to pursue experimentally. Simulations of neuronal networks provide an alternative route to study arbitrarily complex manipulations in morphologically and biophysically detailed models. Here, we present Connectome-Manipulator, a Python framework for rapid connectome manipulations of large-scale network models in SONATA format. In addition to creating or manipulating the connectome of a model, it provides tools to fit parameters of stochastic connectivity models against existing connectomes. This enables rapid replacement of any existing connectome with equivalent connectomes at different levels of complexity, or transplantation of connectivity features from one connectome to another, for systematic study. We employed the framework in a detailed model of rat somatosensory cortex in two exemplary use cases: transplanting interneuron connectivity trends from electron microscopy data and creating simplified connectomes of excitatory connectivity. We ran a series of network simulations and found diverse shifts in the activity of individual neuron populations causally linked to these manipulations.

Investigating visuo-tactile mirror properties in borderline personality disorder: A TMS-EEG study

ObjectivesPatients with borderline personality disorder (pw-BPD) have decreased levels of cognitive empathy, which may be subtended by mirror-like mechanisms in the somatosensory cortices, i.e., the Tactile Mirror System (TaMS). Here, we aimed to shed light on the TaMS and empathic deficits in pw-BPD focusing on connectivity, using transcranial magnetic stimulation and electroencephalography (TMS-EEG). MethodsAfter study preregistration, we collected self-report measures of empathic abilities, behavioral performance in a visuo-tactile spatial congruency task investigating TaMS activity, and TMS-evoked potentials (TEPs) from 20 pw-BPD and 20 healthy controls. TMS was delivered over the right primary somatosensory cortex (S1) during touch observation and real touch delivery. ResultsPw-BPD reported significantly lower levels of cognitive empathy than controls and made significantly more errors in reporting the side of real touches during touch observation. Moreover, pw-BPD presented an altered connectivity pattern from S1-TEPs during touch perception and touch observation, in the last case without differences between human- and object-directed touches. ConclusionsThe results do not support a specific impairment of TaMS in pw-BPD, but reveal significant behavioral and connectivity alterations within the somatosensory network during touch processing. SignificanceThe present findings temper the proposed role of the TaMS in BPD, while still highlighting the involvement of somatosensory network alterations.

Association between the focus of attention and brain activation pattern during golf putting task in amateur and novice: A fNIRS Study

PurposeExternal focus of attention (FOA) has been shown to improve motor performance. However, recent research has found that the effectiveness of FOA is related to the level of expertise. Therefore, this study examined the effects of FOA on putting performance in golfers of different levels of expertise. The neural mechanisms behind FOA were explored in conjunction with fNIRS. MethodA total of 30 participants, including 15 amateurs (Mage: 23.31(SD = 1.32)years; 15 males) and 15 novices (Mage: 22.69(SD = 1.55) years; 11 males; 4 females) were recruited. Participants completed EF and IF golf putting at a duration of 3s per time wearing fNIRS for 3 blocks of 30 seconds interspersed with 10-second rest blocks. ResultBehavioral results showed a significant difference in the putting performance of the amateur group under the EF condition compared to the IF condition (P = 0.019), and relative to novices, the amateur group performed better under the EF condition (P = 0.003). fNIRS results revealed that the amateur group had higher activation levels in the right somatosensory association cortex (RSAC) and right motor cortex (RMC) under the IF condition. In contrast, for the novice group, higher activation levels were observed in the left prefrontal cortex and RMC under the EF condition. ConclusionsOur results revealed SAC and MC over-activation in the amateur group under IF conditions with poor golf putting performance. Our findings suggest that the impairment of automated motor neural networks could be a possible mechanism by which IF affects motor performance with SAC and MC over-activation. Guiding novices to focus on task-related factors consciously could be a potential mechanism by which EF enhances motor performance.

Assembling a physical model helps students grasp human somatosensory pathways.

Mastering the complexity of the nervous system is essential for education programs in physiology, anatomy, and neuroscience. Students often struggle when learning somatosensory pathways, which convey information from sensory neurons to the somatosensory cortex in the brain. Active learning activities incorporating physical models have been shown to increase content comprehension as well as enjoyment of the learning process. Here, we present a three-dimensional physical model of somatosensory pathways constructed of durable, affordable, and widely available materials. In an upper level human physiology lab, students assembled the model and then used it to complete case study questions connecting damage to the spinal cord to resulting sensory deficits. This model-based activity was highly effective as indicated by significant increases in content knowledge and positive responses to survey questions on the effectiveness of the activity. This activity incorporates many evidence-based teaching practices that have been shown to increase engagement, inclusion, and mastery of content and provides an effective and fun way for students to learn a challenging topic.NEW & NOTEWORTHY This model-building activity for learning somatosensory neural pathways increases students' content knowledge and is an enjoyable way to learn a complex system. This activity adds to an ever-growing collection of evidence-based learning activities for human physiology courses.

The analgesic effect of acupuncture in neuropathic pain: regulatory mechanisms of DNA methylation in the brain

Abstract Recent research has demonstrated that chronic pain, resulting from peripheral nerve injury, leads to various symptoms, including not only allodynia and hyperalgesia but also anxiety, depression, and cognitive impairment. These symptoms are believed to arise due to alterations in gene expression and neural function, mediated by epigenetic changes in chromatin structure. Emerging evidence suggests that acupuncture can modulate DNA methylation within the central nervous system, contributing to pain relief and the mitigation of comorbidities. Specifically, acupuncture has been shown to adjust the DNA methylation of genes related to mitochondrial dysfunction, oxidative phosphorylation, and inflammation pathways within cortical regions, such as the prefrontal cortex, anterior cingulate cortex, and primary somatosensory cortex. In addition, it influences the DNA methylation of genes associated with neurogenesis in hippocampal neurons. This evidence indicates that acupuncture, a treatment with fewer side effects compared with conventional medications, could offer an effective strategy for pain management.

Light-Modulated Circadian Synaptic Plasticity in the Somatosensory Cortex: Link to Locomotor Activity

The circadian clock controls various physiological processes, including synaptic function and neuronal activity, affecting the functioning of the entire organism. Light is an important external factor regulating the day–night cycle. This study examined the effects of the circadian clock and light on synaptic plasticity, and explored how locomotor activity contributes to these processes. We analyzed synaptic protein expression and excitatory synapse density in the somatosensory cortex of mice from four groups exposed to different lighting conditions (LD 12:12, DD, LD 16:8, and LL). Locomotor activity was assessed through individual wheel-running monitoring. To explore daily and circadian changes in synaptic proteins, we performed double-immunofluorescence labeling and laser scanning confocal microscopy imaging, targeting three pairs of presynaptic and postsynaptic proteins (Synaptophysin 1/PSD95, Piccolo/Homer 1, Neurexins/PICK1). Excitatory synapse density was evaluated by co-labeling presynaptic and postsynaptic markers. Our results demonstrated that all the analyzed synaptic proteins exhibited circadian regulation modulated by light. Under constant light conditions, only Piccolo and Homer 1 showed rhythmicity. Locomotor activity was also associated with the circadian clock’s effects on synaptic proteins, showing a stronger connection to changes in postsynaptic protein levels. Excitatory synapse density peaked during the day/subjective day and exhibited an inverse relationship with locomotor activity. Continued light exposure disrupted cyclic changes in synapse density but kept it consistently elevated. These findings underscore the crucial roles of light and locomotor activity in regulating synaptic plasticity.

Decoding sensorimotor information from somatosensory cortex by flexible epicortical μECoG arrays in unrestrained behaving rats

Objective.Brain-computer interfaces (BCI) are promising for severe neurological conditions and there are ongoing efforts to develop state-of-the-art neural interfaces, hardware, and software tools. We tested the potential of novel reduced graphene oxide (rGO) electrodes implanted epidurally over the hind limb representation of the primary somatosensory (S1) cortex of rats, and compared them to commercial platinum-iridium (Pt-Ir) 16-channel electrodes (active site diameter: 25μm).Approach.Motor and somatosensory information was decoded offline from microelectrocorticography (μECoG) signals recorded while unrestrained rats performed a simple behavioral task: pressing a lever and the subsequent vibrotactile stimulation of the glabrous skin at three displacement amplitude levels and at two sinusoidal frequencies.μECoG data were initially analyzed by standard time-frequency methods. Next, signal powers of oscillatory bands recorded from multiple electrode channels were used as features for sensorimotor classification by a machine learning algorithm.Main results.Both electrode types performed quite well and similar to each other for predicting the motor interval and the presence of the vibrotactile stimulus. Average accuracies were relatively lower for predicting 3-class vibrotactile frequency and 4-class amplitude level by both electrode types.Significance.Given some confounding factors during the free movement of rats, the results show that both sensory and motor information can be recorded reliably from the hind limb area of S1 cortex by usingμECoG arrays. The chronic use of novel rGO electrodes was demonstrated successfully. The hind limb area may be convenient for the future evaluation of new tools in neurotechnology, especially those for bidirectional BCIs.

Histamine H3 receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization during resting state: an exploratory cortex-wide imaging study in mice

The histaminergic system plays a key role in modulating learning and memory, wakefulness, and energy balance. Histamine H3 receptors constitutively inhibit the synthesis and release of histamine and other neurotransmitters. Therefore, H3 receptor inverse agonists/antagonists increase the synthesis and release of these neurotransmitters, enhancing cognitive functions, including memory consolidation and retrieval. Spontaneous neural activity across the cerebral cortex is essential for cognitive function, including memory consolidation. Abnormal spontaneous activity has, in fact, been associated with cognitive dysfunctions and psychiatric disorders. Given the cognitive improvement achieved with the use of H3 receptor inverse agonists/antagonists, we examined the effects of two inverse agonists/antagonists – thioperamide and pitolisant – on spontaneous cortical activity, using in vivo wide-field Ca2+ imaging. Changes in cortical activity, across multiple cortical regions and in inter-regional connectivity, from pre- to post-administration were evaluated using a linear support vector machine decoder. Thioperamide and pitolisant both modified the amplitude distribution of calcium events across multiple cortical regions, including a reduction in the frequency of low-amplitude calcium events in the somatosensory cortex. Graph theory analysis revealed increases in centrality measures in the somatosensory cortex with the use of both thioperamide and pitolisant, indicative of their importance in the organization of cortical networks. These findings indicate that H3 receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization of activity in the cerebral cortex during the resting state.

Spatial mapping of activity changes across sensory areas following visual deprivation in adults.

Loss of a sensory modality triggers global adaptation across brain areas, allowing the remaining senses to guide behavior more effectively. There are specific synaptic and circuit plasticity observed across many sensory areas, which suggests potential widespread changes in activity. Here we used a cFosTRAP2 mouse line to drive tdTomato (tdT) expression in active cells to spatially map the extent of activity changes in various sensory areas in adult mice of both sexes following two modes of visual deprivation. We found that in the primary visual cortex (V1) both dark exposure (DE) and enucleation (EN) caused an initial loss of active cells followed by a partial rebound, which occurred relatively more in the superficial layers. A similar pattern was observed in the secondary visual cortex, especially in the lateral areas (V2L). The spared primary sensory cortices adapted distinctly. In the primary somatosensory barrel cortex (S1BF) there was a change in the density of active cells dependent on the duration and the mode of visual deprivation. In the primary auditory cortex (A1), there was a relative reduction in the density of active cells in the superficial layers without a significant change in the overall density. There were minimal changes in the active cell density in the secondary cortices of the spared senses and the multisensory retrosplenial cortex (RSP). Our results are consistent with cross-modal recruitment of the deprived visual cortex and compensatory plasticity in the spared primary sensory cortices that can support enhanced processing and refinement of the spared senses.Significance Statement The neural basis for improved processing of the spared senses after losing vision is largely dependent on plasticity mechanisms driven by neural activity. Using a transgenic mouse model to label active neurons in a temporally controlled manner, this study reveals the spatial pattern of widespread activity changes across brain areas following visual deprivation in adult mice. The findings suggest that the deprived visual cortex undergoes an initial reduction in activity followed by a rebound suggestive of cross-modal recruitment. Activity changes in the spared primary sensory cortices conform to compensatory plasticity, which could support improved processing of the spared senses. The results highlight the presence of large-scale plasticity in the adult brain to compensate for loss of vision.

Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30s. Correspondingly, two-photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

Long-lasting, subtype-specific regulation of somatostatin interneurons during sensory learning.

Somatostatin (SST)-expressing inhibitory neurons are a major class of neocortical γ-amino butyric acid (GABA) neurons, where morphological, electrophysiological, and transcriptomic analyses indicate more than a dozen different subtypes. However, whether this diversity is related to specific roles in cortical computations and plasticity remains unclear. Here we identify learning-dependent, subtype-specific plasticity in layer 2/3 SST neurons of the mouse somatosensory cortex. Martinotti-type, SST neurons expressing calbindin-2 show a selective decrease in excitatory synaptic input and stimulus-evoked calcium responses as mice learn a stimulus-reward association. Using these insights, we develop a label-free classifier using basal activity from in vivo imaging that accurately predicts learning-associated response plasticity. Our data indicate that molecularly-defined SST neuron subtypes play specific and highly-regulated roles in sensory information processing and learning.

Localization of brain neuronal IL-1R1 reveals specific neural circuitries responsive to immune signaling

Interleukin-1 (IL-1) is a pro-inflammatory cytokine that exerts a wide range of neurological and immunological effects throughout the central nervous system (CNS) and is associated with the etiology of affective and cognitive disorders. The cognate receptor for IL-1, Interleukin-1 Receptor Type 1 (IL-1R1), is primarily expressed on non-neuronal cells (e.g., endothelial cells, choroidal cells, ventricular ependymal cells, astrocytes, etc.) throughout the brain. However, the presence and distribution of neuronal IL-1R1 (nIL-1R1) has been controversial. Here, for the first time, a novel genetic mouse line that allows for the visualization of IL-1R1 mRNA and protein expression (Il1r1GR/GR) was used to map all brain nuclei and determine the neurotransmitter systems which express nIL-1R1 in adult male mice. The direct responsiveness of nIL-1R1-expressing neurons to both inflammatory and physiological levels of IL-1β in vivo was tested. Neuronal IL-1R1 expression across the brain was found in discrete glutamatergic and serotonergic neuronal populations in the somatosensory cortex, piriform cortex, dentate gyrus, and dorsal raphe nucleus. Glutamatergic nIL-1R1 comprises most of the nIL-1R1 expression and, using Vglut2-Cre-Il1r1r/r mice, which restrict IL-1R1 expression to only glutamatergic neurons, an atlas of glutamatergic nIL-1R1 expression across the brain was generated. Analysis of functional outputs of these nIL-1R1-expressing nuclei, in both Il1r1GR/GR and Vglut2-Cre-Il1r1r/r mice, reveals IL-1R1+ nuclei primarily relate to sensory detection, processing, and relay pathways, mood regulation, and spatial/cognitive processing centers. Intracerebroventricular (i.c.v.) injections of IL-1 (20 ng) induces NFκB signaling in IL-1R1+ non-neuronal cells but not in IL-1R1+ neurons, and in Vglut2-Cre-Il1r1r/r mice IL-1 did not change gene expression in the dentate gyrus of the hippocampus (DG). GO pathway analysis of spatial RNA sequencing 1mo following restoration of nIL-1R1 in the DG neurons reveals IL-1R1 expression downregulates genes related to both synaptic function and mRNA binding while increasing select complement markers (C1ra, C1qb). Further, DG neurons exclusively express an alternatively spliced IL-1R Accessory protein isoform (IL-1RAcPb), a known synaptic adhesion molecule. Altogether, this study reveals a unique network of neurons that can respond directly to IL-1 via nIL-1R1 through non-autonomous transcriptional pathways; earmarking these circuits as potential neural substrates for immune signaling-triggered sensory, affective, and cognitive disorders.

Meditation expertise influences response bias and prestimulus alpha activity in the somatosensory signal detection task.

This study investigates the proposed mechanism of mindfulness, its impact on body awareness and interoception, and its potential benefits for mental and physical health. Using psychophysical assessments, we compared 31 expert meditators with 33 matched controls (non-meditators who engage in regular reading, more than 5 h per week) in terms of somatosensory accuracy with a somatosensory signal detection task (SSDT) and interoceptive sensibility via self-report measures. We hypothesized that meditators would demonstrate superior somatosensory accuracy, indicative of heightened body awareness, potentially linked to increased alpha modulation in the somatosensory cortex, as observed via electroencephalography (EEG). In the SSDT, participants attempted to detect near-threshold tactile stimuli presented with a non-informative light in half of the trials. Contrary to our expectations, the findings showed that meditators had a lower decision threshold rather than higher accuracy. EEG results corroborated earlier research, indicating reduced prestimulus alpha power in meditators, suggesting enhanced alpha modulation. Furthermore, a trial-by-trial analysis revealed a negative correlation between prestimulus alpha activity and tactile perception. Compared to controls, meditators also reported greater interoceptive sensibility, less emotional suppression, and fewer difficulties in describing feelings. These findings may imply that enhanced tactile perception is associated with lower prestimulus alpha activity by reducing sensory filtering in the somatosensory cortex, thus increasing response rates without necessarily improving accuracy among meditators.

Disruption of the autism-associated Pcdh9 gene leads to transcriptional alterations, synapse overgrowth, and defective network activity in the CA1.

Protocadherins, a family of adhesion molecules with crucial role in cell-cell interactions, have emerged as key players in neurodevelopmental and psychiatric disorders. In particular, growing evidence links genetic alterations in Protocadherin 9 (PCDH9) gene with Autism Spectrum Disorder (ASD) and Major Depressive Disorder (MDD). Furthermore, Pcdh9 deletion induces neuronal defects in the mouse somatosensory cortex, accompanied by sensorimotor and memory impairment. However, the synaptic and molecular mechanisms of PCDH9 in the brain remain largely unknown, particularly concerning its impact on brain pathology. To address this question, we conducted a comprehensive investigation of PCDH9 role in the male mouse hippocampus at the ultrastructural, biochemical, transcriptomic, electrophysiological and network level. We show that PCDH9 mainly localizes at glutamatergic synapses and its expression peaks in the first week after birth, a crucial time window for synaptogenesis. Strikingly, Pcdh9 KO neurons exhibit oversized presynaptic terminal and postsynaptic density (PSD) in the CA1. Synapse overgrowth is sustained by the widespread up-regulation of synaptic genes, as revealed by single-nucleus RNA-seq (snRNA-seq), and the dysregulation of key drivers of synapse morphogenesis, including the SHANK2/CORTACTIN pathway. At the functional level, these structural and transcriptional abnormalities result into increased excitatory postsynaptic currents (mEPSC) and reduced network activity in the CA1 of Pcdh9 KO mice. In conclusion, our work uncovers Pcdh9 pivotal role in shaping the morphology and function of CA1 excitatory synapses, thereby modulating glutamatergic transmission within hippocampal circuits.Significance statement Converging evidence indicates that genetic alterations in Protocadherin 9 (PCDH9) gene are associated with Autism Spectrum Disorder (ASD) and Major Depressive Disorder (MDD). However, our understanding of PCDH9 physiological role and molecular mechanisms in the brain, as well as its connection to synaptic dysfunction and brain pathology, remains limited. Here we demonstrate that Pcdh9 regulates the transcriptional profile, morphology and function of glutamatergic synapses in the CA1, thereby tuning hippocampal network activity. Our results elucidate the molecular and synaptic mechanisms of a gene implicated in neurodevelopmental and psychiatric disorders, and suggest potential hippocampal alterations contributing to the cognitive deficits associated with these conditions.

Electroacupuncture Regulates Cannabinoid Receptor 1 Expression in a Mouse Fibromyalgia Model: Pharmacological and Chemogenetic Modulation.

Fibromyalgia is a chronic illness usually accompanied by long-lasting, general pain throughout the body, often accompanied by anxiety, depression, fatigue, and sleep disruption. Meanwhile, doctors and scientists have not entirely discovered detailed mechanisms; patients always have an exaggerated sensation to pervasive pain without satisfied medical service. Given the lack of knowledge on its underlying mechanism, current treatments aim to provide pain and/or symptom relief. The present study aimed to clarify the role of cannabinoid receptor 1 (CB1) signaling in a mouse fibromyalgia pain model. To develop the mouse fibromyalgia model, mice were subjected to intermittent cold stress (ICS). Our results indicated that mechanical (2.09 ± 0.09 g) and thermal hyperalgesia (4.77 ± 0.29 s), which were evaluated by von Frey and Hargraves' tests, were induced by ICS, suggesting successful modeling. The hurting replies were then provoked by electroacupuncture (EA) but not for sham EA mice. Further, in a Western blot analysis, we found significantly decreased CB1 protein levels in the thalamus, somatosensory cortex, and anterior cingulate cortex. In addition, the levels of pain-related protein kinases and transcription factor were increased. Treatment with EA reliably increased CB1 expression in various brain regions sequentially alleviated by nociceptive mediators. Furthermore, the administration of a CB1 agonist significantly attenuated fibromyalgia pain, reversed EA analgesia by the CB1 antagonist, and further reversed the chemogenetic inhibition of SSC. Our innovative findings evidence the role of CB1 signaling in the interaction of EA and fibromyalgia, suggesting its potential for clinical trials and as a treatment target.