A glutamatergic innervation from medial area of secondary visual cortex to lateral posterior thalamic nucleus facilitates nociceptive and neuropathic pain.

Neuropathic pain involves complex cortical mechanisms, yet the role of the medial secondary visual cortex (V2M) remains poorly understood. We hypothesized that glutamatergic neurons in V2M (V2M) contribute to pain modulation and explored their functional involvement in both normal and neuropathic pain states. Here, we found that V2M could be activated by peripheral stimulation under normal conditions.

Low-Frequency Stimulation at the Ventromedial Hypothalamus Exhibits Broad-Spectrum Efficacy Across Models of Epilepsy.

Aims: The limited efficacy and very restricted antiseizure range of current deep brain stimulation (DBS) targets highlight the need to find an optimal target for managing various seizure types. Here, we aimed to investigate the efficacy of DBS on the ventromedial hypothalamus (VMH) in the different types of experimental epileptic seizures.

Methods: The efficacy of DBS was examined in various epileptic seizure models, and the potential mechanisms were investigated by using in vivo calcium signal recording and optogenetics.

EEG signature orchestrating expression of ictal behavior in mesial temporal lobe epilepsy.

Objectives: We investigated EEG features differentiating clinical seizures (CSs) from subclinical seizures (SCSs) to explore the mechanisms underlying the generation of ictal behavior in mesial temporal lobe epilepsy (mTLE).

Methods: Peri-ictal state of power spectral density (PSD) within seizure onset zone (SOZ) and propagation zone (PZ) were compared between SCSs and CSs. Functional connectivity was analyzed using the nonlinear correlation coefficient h, outgoing links (OUT) and ingoing links (IN).

Prediction of Pharmacoresistance in Drug-Naïve Temporal Lobe Epilepsy Using Ictal EEGs Based on Convolutional Neural Network.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis.

Circuit Reorganization of Subicular Cell-Type-Specific Interneurons in Temporal Lobe Epilepsy.

The subiculum represents a crucial brain pivot in regulating seizure generalization in temporal lobe epilepsy (TLE), primarily through a synergy of local GABAergic and long-projecting glutamatergic signaling. However, little is known about how subicular GABAergic interneurons are involved in a cell-type-specific way. Here, employing Ca fiber photometry, retrograde monosynaptic viral tracing, and chemogenetics in epilepsy models of both male and female mice, we elucidate circuit reorganization patterns mediated by subicular cell-type-specific interneurons and delineate their functional disparities in seizure modulation in TLE.

Enriched Environment Reduces Seizure Susceptibility via Entorhinal Cortex Circuit Augmented Adult Neurogenesis.

Enriched environment (EE), characterized by multi-sensory stimulation, represents a non-invasive alternative for alleviating epileptic seizures. However, the mechanism by which EE exerts its therapeutic impact remains incompletely understood. Here, it is elucidated that EE mitigates seizure susceptibility through the augmentation of adult neurogenesis within the entorhinal cortex (EC) circuit.

Caspase-1 inhibitor CZL80 protects against acute seizures via amplifying the inhibitory neural transmission.

Current anti-seizure medications (ASDs) primarily target ion channels or neurotransmissions; however, their practicability is limited by unwanted side-effects and pharmacoresistance. Cumulative evidence has proposed pro-inflammatory caspase-1 as a potential target for developing ASDs. In this study, we showed that the small-molecular caspase-1 inhibitor CZL80 can prevent seizures in various models including the maximal electroshock (MES), the pentylenetetrazol (PTZ), and the amygdaloid kindled models.

Histamine H receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice.

Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H receptor (HR) exerts critical and intricate effects on fear memory, the role of HR is still not clarified. Here, we show that deletion of HR gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice.

Current advances in rodent drug-resistant temporal lobe epilepsy models: Hints from laboratory studies.

Anti-seizure drugs (ASDs) are the first choice for the treatment of epilepsy, but there is still one-third of patients with epilepsy (PWEs) who are resistant to two or more appropriately chosen ASDs, named drug-resistant epilepsy (DRE). Temporal lobe epilepsy (TLE), a common type of epilepsy usually associated with hippocampal sclerosis (HS), shares the highest proportion of drug resistance (approximately 70%). In view of the key role of the temporal lobe in memory, emotion, and other physiological functions, patients with drug-resistant temporal lobe epilepsy (DR-TLE) are often accompanied by serious complications, and surgical procedures also yield extra considerations.

Low-frequency stimulation in the zona incerta attenuates seizure via driving GABAergic neuronal activity.

Background: Managing refractory epilepsy presents a significant a substantial clinical challenge. Deep brain stimulation (DBS) has emerged as a promising avenue for addressing refractory epilepsy. However, the optimal stimulation targets and effective parameters of DBS to reduce seizures remian unidentified.

Low-frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy.

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus. It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy, but still lacks effective treatments. Here, we aimed to test the effects of low-frequency stimulation (LFS) at the subiculum for secondary epileptogenesis in a mouse model.

Widespread slow oscillations support interictal epileptiform discharge networks in focal epilepsy.

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation.

The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology.

Ample evidence has suggested the stress etiology of depression, but the underlying mechanism is not fully understood yet. Here, we report that chronic social defeat stress (CSDS) attenuates the excitatory output of the claustrum (CLA) to the prelimbic cortex (PL) through the dynorphin/κ-opioid receptor (KOR) signaling, being critical for depression-related behaviors in male mice. The CSDS preferentially impairs the excitatory output from the CLA onto the parvalbumin (PV) of the PL, leading to PL micronetwork dysfunction by disinhibiting pyramidal neurons (PNs).

Projection-defined median raphe Pet subpopulations are diversely implicated in seizure.

The raphe nuclei, the primary resource of forebrain 5-HT, play an important but heterogeneous role in regulating subcortical excitabilities. Fundamental circuit organizations of different median raphe (MR) subsystems are far from completely understood. In the present study, using cell-specific viral tracing, Ca fiber photometry and epilepsy model, we map out the forebrain efferent and afferent of different MR Pet subpopulations and their divergent roles in epilepsy.

Satellite glial cells in sensory ganglia play a wider role in chronic pain via multiple mechanisms.

Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons. An increasing body of evidence suggests that in the presence of inflammation and nerve damage, a significant number of satellite glial cells become activated, thus triggering a series of functional changes. This suggests that satellite glial cells are closely related to the occurrence of chronic pain.

Chemogenetic inhibition of subicular seizure-activated neurons alleviates cognitive deficit in male mouse epilepsy model.

Cognitive deficit is a common comorbidity in temporal lobe epilepsy (TLE) and is not well controlled by current therapeutics. How epileptic seizure affects cognitive performance remains largely unclear. In this study we investigated the role of subicular seizure-activated neurons in cognitive impairment in TLE.