The Role of the Insular Cortex in Pain

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5736 - 5736

Published: March 17, 2023

The transition from normal to chronic pain is believed involve alterations in several brain areas that participate the perception of pain. These plastic changes are then responsible for aberrant and comorbidities. insular cortex consistently found activated studies patients. Functional insula contribute pain; however, complex mechanisms by which involved under pathological conditions still not clear. In this review, an overview function provided findings on its role human summarized. Recent progress preclinical experimental models reviewed, connectivity with other regions examined shed new light neuronal cortex’s contribution sensation. This review underlines need further underlying involvement chronicity expression comorbid disorders.

Language: Английский

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Social circuits and their dysfunction in autism spectrum disorder

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3194 - 3206

Published: Aug. 1, 2023

Social behaviors, how individuals act cooperatively and competitively with conspecifics, are widely seen across species. Rodents display various social many different behavioral paradigms have been used for investigating their neural circuit bases. behavior is highly vulnerable to brain network dysfunction caused by neurological neuropsychiatric conditions such as autism spectrum disorders (ASDs). Studying mouse models of ASD provides a promising avenue toward elucidating mechanisms abnormal potential therapeutic targets treatment. In this review, we outline recent progress key findings on underlying behavior, particular emphasis rodent studies that monitor manipulate the activity specific circuits using modern systems neuroscience approaches. mediated distributed brain-wide among major cortical (e.g., medial prefrontal cortex (mPFC), anterior cingulate cortex, insular (IC)) subcortical nucleus accumbens, basolateral amygdala (BLA), ventral tegmental area) structures, influenced multiple neuromodulatory oxytocin, dopamine, serotonin). We particularly draw special attention IC unique area mediates multisensory integration, encoding ongoing interaction, decision-making, emotion, empathy. Additionally, synthesis demonstrates dysfunctions in mPFC-BLA circuitry neuromodulation prominent. Pharmacological rescues local or systemic oral) administration drugs provided valuable clues developing new agents ASD. Future efforts technological advances will push forward next frontiers field, elucidation inter-brain dynamics during real virtual interactions, establishment circuit-based therapy affecting functions.

Language: Английский

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VIP interneuron impairment promotes in vivo circuit dysfunction and autism-related behaviors in Dravet syndrome

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112628 - 112628

Published: June 1, 2023

Dravet syndrome (DS) is a severe neurodevelopmental disorder caused by loss-of-function variants in SCN1A, which encodes the voltage-gated sodium channel subunit Nav1.1. We recently showed that neocortical vasoactive intestinal peptide interneurons (VIP-INs) express Nav1.1 and are hypoexcitable DS (Scn1a+/−) mice. Here, we investigate VIP-IN function at circuit behavioral level performing vivo 2-photon calcium imaging awake wild-type (WT) Scn1a+/− pyramidal neuron activation during transition from quiet wakefulness to active running diminished mice, optogenetic of VIP-INs restores activity WT levels locomotion. selective Scn1a deletion reproduces core autism-spectrum-disorder-related behaviors addition cellular- circuit-level deficits function, but without epilepsy, sudden death, or avoidance seen global model. Hence, impaired vivo, may underlie non-seizure cognitive comorbidities DS.

Language: Английский

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Author response: Bidirectional fear modulation by discrete anterior insular circuits in male mice

Published: July 16, 2024

The brain's ability to appraise threats and execute appropriate defensive responses is essential for survival in a dynamic environment. Humans studies have implicated the anterior insular cortex (aIC) subjective fear regulation its abnormal activity fear/anxiety disorders. However, complex aIC connectivity patterns involved regulating remain under investigated. To address this, we recorded single units of freely moving male mice that had previously undergone auditory conditioning, assessed effect optogenetically activating specific output structures fear, examined organization neurons projecting with retrograde tracing. Single-unit recordings revealed balanced number pyramidal neurons' either positively or negatively correlated conditioned tone-induced freezing (fear) response. Optogenetic manipulations neuronal during tone presentation altered expression freezing. Neural tracing showed non-overlapping populations project amygdala medial thalamus, pathway bidirectionally modulated fear. Specifically, optogenetic stimulation aIC-amygdala increased freezing, while aIC-medial thalamus decreased it. Our findings suggest balance freezing-excited freezing-inhibited distinct efferent circuits interact collectively modulate behavior.

Language: Английский

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Anterior Cingulate Cortex–Anterior Insular Cortex Circuit Mediates Hyperalgesia in Adolescent Mice Experiencing Early Life Stress

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: 16(5), P. 920 - 931

Published: Feb. 17, 2025

Understanding neurobiological mechanisms underlying changes in behavior and neural activity caused by early life stress (ELS) is essential for improving these adverse outcomes individuals. ELS incited exposure to maternal separation (MS) can be defined as a form of social pain, but little known about the mechanism adolescents with ELS-induced pain sensitization. Employing an MS-induced paradigm mice, we reported here that both male female MS mice aged 1-2 months exhibited mechanical thermal hyperalgesia using paw-withdrawal hot/cold plate tests. The increased high gamma (γhigh) oscillations accompanied activation parvalbumin-positive interneurons (PVINs) anterior insular cortex (AIC), not cingulate (ACC), were shown mice. Moreover, ACC-driven AIC connectivity was enhanced characterized amplified phase coherence delta (δ) theta (θ) bands escalation coupling ACC θ γ amplitude. Chemogenetic inactivation PVINs relieved altered ACC-AIC observed increase δ-θ synchronization PVIN circuit indicates this pathway therapeutic target hyperalgesia.

Language: Английский

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Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following discovery they predominantly function by inhibiting dendritic-targeting somatostatin (SST) disinhibiting PCs. This VIP-SST disinhibitory motif is observed throughout neocortex from mice humans, serves as a key mechanism for top-down (feedback) context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found play an important role in sensory processing, executive functions, attention, sensorimotor integration cortico-cortical thalamocortical feedback interactions. Furthermore, implicated mediating effects reinforcement signals, both reward aversive, via their responsiveness neuromodulators such acetylcholine (ACh), facilitating synaptic plasticity learning. While it evident transcriptomic analyses molecularly heterogeneous group, physiological significance this diversity unclear at present. Here, we characterized functional primary somatosensory cortex leveraging intersectional genetic approaches study IN subtypes. We can be divided into four different populations: group expresses Ca 2+ -binding protein calretinin (CR), two groups express cholecystokinin (CCK), does not either CR or CCK (non-CCK non-CR; nCCK nCR). neurons each exhibit laminar distributions, axonal dendritic arbors, intrinsic electrophysiological properties, efferent connectivity, VIP/CR target almost exclusively SST VIP/nCCK nCR also mainly but connections parvalbumin (PV) INs. These essentially no connectivity (PCs). On hand, VIP/CCK PCs, differ degree which release type modulated endocannabinoids. long-range inputs differentially recruit groups. Intriguingly, find populations subtypes turn, indicating presence specialized subcircuits. Activation subpopulations vivo results differential on network, thus providing evidence modularity actions during

Language: Английский

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Decoding Social Touch: A Multi-Modal Exploration of Tactile Perception, Gender and Culture

Physiology & Behavior, Journal Year: 2025, Volume and Issue: unknown, P. 114918 - 114918

Published: April 1, 2025

Social touch plays a vital role in human development, communication, and general well-being. However, the mechanisms underlying how social elicits pleasant or aversive responses are poorly understood. Furthermore, it remains unclear alterations sensory processing, at both perceptual level (i.e. detection discrimination of stimuli) behavioural response to stimuli), shape experience touch, addition contextual factors such as gender culture. In current study, we used vibrotactile psychophysics novel paradigm assess association between tactile differences preference two cross-cultural cohorts (54 adults UK 21 Singapore). We found that participants with poorer thresholds had lower pleasantness ratings for higher non-social stronger predictive effect than culture alone. also evidence strong effects, female rated different-gender less males. Singaporean showed preferences participants. Our results suggest bottom-up mechanism linking greater aversion adults. while some cultural were observed level, contributions appeared be conserved, suggesting shared biological cultures. These findings could have implications clinical conditions characterised by altered processing.

Language: Английский

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Deciphering the functional role of insular cortex stratification in trigeminal neuropathic pain

The Journal of Headache and Pain, Journal Year: 2024, Volume and Issue: 25(1)

Published: May 10, 2024

Abstract Trigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) thought involve several neuroplastic changes multiple brain regions, resulting distorted perception associated comorbidities. While functional insula are recognized contributors TNP, intricate mechanisms underlying involvement processing remain subjects ongoing investigation. Here, we have overviewed most recent advancements regarding role IC regulating alongside insights into IC’s connectivity with other regions implicated trigeminal pathways. In addition, review examines diverse modulation strategies that target different parts IC, thereby suggesting novel diagnostic therapeutic management future.

Language: Английский

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Localization and Registration of 2D Histological Mouse Brain Images in 3D Atlas Space

Neuroinformatics, Journal Year: 2023, Volume and Issue: 21(3), P. 615 - 630

Published: June 26, 2023

To accurately explore the anatomical organization of neural circuits in brain, it is crucial to map experimental brain data onto a standardized system coordinates. Studying 2D histological mouse slices remains standard procedure many laboratories. Mapping these challenging; due deformations, artifacts, and tilted angles introduced during preparation slicing process. In addition, analysis can be highly dependent on level expertise human operator. Here we propose computational tool for Accurate Mouse Brain Image Analysis (AMBIA), 3D model with minimal intervention. AMBIA has modular design that comprises localization module registration module. The deep learning-based pipeline localizes single slice Allen Atlas generates corresponding atlas plane. built upon Ardent python package performs deformable between its atlas. By comparing AMBIA's performance ratings, demonstrate at expert level. provides an intuitive efficient way accurate images digital Our graphical user interface designed used by researchers programming knowledge.

Language: Английский

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The role of subicular VIP-expressing interneurons on seizure dynamics in the intrahippocampal kainic acid model of temporal lobe epilepsy

Experimental Neurology, Journal Year: 2023, Volume and Issue: 370, P. 114580 - 114580

Published: Oct. 24, 2023

The subiculum, a key output region of the hippocampus, is increasingly recognized as playing crucial role in seizure initiation and spread. subiculum consists glutamatergic pyramidal cells, which show alterations intrinsic excitability course epilepsy, multiple types GABAergic interneurons, exhibit varying characteristics epilepsy. In this study, we aimed to assess vasoactive intestinal peptide interneurons (VIP-INs) ventral pathophysiology temporal lobe We observed that an anatomically restricted inhibition VIP-INs was sufficient reduce seizures intrahippocampal kainic acid model changing circadian rhythm seizures, emphasizing critical small cell population modulating TLE. As expected, permanent unilateral or bilateral silencing non-epileptic animals did not induce epileptiform activity. Interestingly, transient activation enough increase frequency acute model. Our results offer new perspectives on involvement Given predominant disinhibitory input subicular microcircuits, modifications could be considered development therapeutic strategies improve control.

Language: Английский

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