Superficial Layers Research Articles

Alpha-2 nicotinic acetylcholine receptors regulate spectral integration in auditory cortex

IntroductionIn primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)—inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites. Auditory inputs to PCs include thalamocortical inputs to middle layers relaying information about characteristic frequency (CF) and near-CF stimuli, and intracortical long-distance (“horizontal”) projections to multiple layers carrying information about spectrally distant (“nonCF”) stimuli. CF and nonCF inputs integrate to create broad frequency receptive fields (RFs). Systemic administration of nicotine activates nAChRs to “sharpen” RFs—to increase gain within a narrowed RF—resulting in enhanced responses to CF stimuli and reduced responses to nonCF stimuli. While nicotinic mechanisms to increase gain have been identified, the mechanism underlying RF narrowing is unknown.MethodsHere, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted.ResultsThe distribution of fluorescent neurons in auditory cortex was consistent with previous studies demonstrating α2 nAChRs in layer 5 MCs, including nonpyramidal somata in layer 5 and dense processes in layer 1. We also observed label in subcortical auditory regions, including processes, but no somata, in the medial geniculate body, and both fibers and somata in the inferior colliculus. Using electrophysiological (current-source density) recordings in α2 nAChR knock-out mice, we found that systemic nicotine failed to enhance CF-evoked inputs to layer 4, suggesting a role for subcortical α2 nAChRs, and failed to reduce nonCF-evoked responses, suggesting that α2 nAChRs regulate horizontal projections to produce RF narrowing.DiscussionThe results support the hypothesis that α2 nAChRs function to simultaneously enhance RF gain and narrow RF breadth in A1. Notably, a similar neural circuit may recur throughout cortex and hippocampus, suggesting widespread conserved functions regulated by α2 nAChRs.

Outcomes Following Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus at 10-Year Follow-Up: A Retrospective Review.

The purpose of this study was to evaluate outcomes following autologous osteochondral transplantation (AOT) for the treatment of osteochondral lesions of the talus (OLT) at a minimum of 10-year follow-up. Retrospective chart review identified patients who underwent AOT for the treatment of OLT. Pre-operative magnetic resonance imaging (MRI) scans were obtained in all patients. Clinical outcomes assessed included: pre- and post-operative foot and ankle outcome score (FAOS), visual analog scale (VAS), patient satisfaction, complications, failures and secondary surgical procedures. Thirty-nine patients with a mean lesion size was 122.3 ± 64.1 mm2 and mean follow-up time of 138.9 ± 16.9 months were included. The mean FAOS scores improved from a preoperative score of 51.9 ± 16.0 to 75.3 ± 21.9 (P < 0.001). Increasing lesion size was variable associated with inferior FAOS scores (R2 = 0.2228). There was statistically significant higher mean T2 relaxation values at the superficial layer at the site of the AOT graft (42.9 ± 5.2 ms) compared to the superficial layer of the adjacent native cartilage (35.8 ± 3.8 ms) (P < 0.001). Seventeen complications (43.6%) were observed, the most common of which was anterior ankle impingement (25.6%). There were 2 failures (5.1%), both of which had a history of prior bone marrow stimulation via microfracture and post-operative cysts identified on MRI. This retrospective review found that AOT for the treatment of large OLTs produced a 94.9% survival rate at a minimum of 10-year follow-up. Increasing lesion size was associated with inferior clinical outcomes. The findings of this study indicates that AOT is a viable long-term surgical strategy for the treatment of large OLTs.

Acupuncture Point Selection Strategies for Treating Hyperhidrosis.

Hyperhidrosis is a condition defined by excessive sweating caused by various underlying factors, and it is commonly encountered in clinical practice. It may occur alone or as a symptom associated with other diseases, and is closely linked to the functions of the five organs as well as the metabolism of Qi, blood, and bodily fluids. This article summarizes relevant literature regarding acupuncture treatment for hyperhidrosis, focusing on aspects such as external and internal factors, deficiency and excess conditions, the interplay between nutritive and defensive Qi, Qi and blood dynamics, organ systems, and experiential point selection. Additionally, it discusses initial strategies for point selection, highlighting the importance of syndrome differentiation in clinical practice. The initial step should be to identify the Yin and Yang to understand the fundamental principles, followed by a comprehensive evaluation of symptoms in relation to organ systems, superficial and deep layers, cold and heat conditions, and deficiency and excess. This approach allows for flexible prescribing aimed at harmonizing Yin and Yang.

Soft-tissue keratocyst: report of 3 new cases from Brazil.

To describe the clinicopathological features of 3 new cases of soft-tissue keratocyst (STK) of the buccal mucosa from Brazil. Clinical data from 3 patients diagnosed with STK were obtained from the archives of the Laboratory of Oral Pathology at the Federal University of Rio de Janeiro- Brazil from 2020 to 2023. Two oral pathologists reviewed conventional hematoxylin and eosin-stained slides of each case. Immunohistochemical stainings for CK19, Bcl-2, CD138, D2-40, EMA, and Ki-67 were performed in all cases. Case 1 was a 58-year-old man with a 2-year history of painless swelling of the right buccal mucosa, measuring approximately 5cm. Case 2 was of a 44-year-old man with a painful swelling in the left buccal mucosa lasting 3 years with drainage to the oral cavity. Case 3 was of a 74-year-old woman with a painful swelling in the left buccal mucosa of unknown duration. Microscopic evaluation of all 3 cases revealed a cyst lined with a few cell layers composed of columnar palisading basal cells and a corrugated parakeratin surface. The capsule comprised fibrous connective tissue with variable amounts of blood vessels with hemorrhage, nerve bundles, fat tissue, striated muscle fibers, and the absence of pilosebaceous units. No recurrence was observed after complete surgical removal. All epithelial layers of the 3 cases expressed positivity for CK19 and CD138, the basal cells were positive for Bcl-2 and D2-40, and the superficial epithelial layer was positive for EMA. All cases demonstrated a low proliferation index by Ki-67. This study represents a series of 3 cases of STK that affected the posterior buccal mucosa of middle-aged patients from Brazil, sharing histopathological and immunohistochemical features with odontogenic keratocyst.

Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy.

Coordination Regulation Strategy in Fabricating Bi2S3@CNFs Composites with Uniform Dispersion for Robust Sodium Storage.

To solve large volume change and low conductivity of Bi2S3-based anodes, a coordination regulation strategy is proposed to prepare Bi2S3 nanoparticles dispersed in carbon fiber (Bi2S3@CNF) composites. It has been discovered that introducing trimesic acid as a ligand can significantly improve the loading and dispersion of Bi3+ in polyacrylonitrile fibers. The results exhibit that Bi2S3 nanoparticles of 200-300 nm are uniformly anchored on the superficial surface layer of CNFs, and Bi2S3 nanoparticles of about 20 nm are evenly dispersed in the interior of CNFs. Assessed as sodium-ion batteries' anode material, the discharge capacity of the Bi2S3@CNF anode in the second cycle is 669.3 mAh g-1 at 0.1 A g-1 and still retains 620.2 mAh g-1 after 100 cycles, with the capacity retention rate of 92.7%. Even at 0.5 A g-1, the specific capacity of the second cycle is 432.99 mAh g-1, which still keeps 400.9 mAh g-1 after 800 cycles, with a retention rate of 92.5%. The excellent cycle stability is mainly attributed to the uniform distribution of small Bi2S3 nanoparticles in CNFs providing abundant active sites, preventing side reactions, relieving volume expansion, improving the electrical conductivity, and accelerating the electrochemical reaction kinetics.

Laminar fMRI in the locked-in stage of amyotrophic lateral sclerosis shows preserved activity in layer Vb of primary motor cortex

Amyotrophic lateral sclerosis (ALS) affects the cerebral cortex layer-dependently, most notably by the foremost targeting of upper motor neurons (UMNs) sited in layer Vb. Previous studies have shown a retained ability of paralysed patients to activate cortical motor networks, even in late-stage ALS. However, it is currently unknown whether such activation reflects a retained capacity to process sensorimotor inputs or if it is a result of actual motor output. Given the distinct function of individual cortical layers, layer-specific functional measurements may provide insight to this question. In this study, using submillimetre resolution laminar fMRI, we assessed the layer-dependent activation associated with attempted (motor) and passive (somatosensory) movements in a locked-in stage ALS patient. We found robust activation in both superficial and deep layers of primary motor cortex (M1). The peak activation in deep layers was localised to layer Vb. These findings demonstrate preserved activity in deep output layers of M1, possibly reflecting a retained ability to engage surviving UMNs despite years of paralysis. Our study underscores the capacity of laminar fMRI to discern subtle cortical activity and elucidates a promising pathway for probing in vivo human ALS pathology with unprecedented resolution.

Layer-specific dynamics of local field potentials in monkey V1 during electrical stimulation.

The mammalian neocortex, organized into six cellular layers or laminae, forms a cortical network within layers. Layer specific computations are crucial for sensory processing of visual stimuli within primary visual cortex. Laminar recordings of local field potentials (LFPs) are a powerful tool to study neural activity within cortical layers. Electric brain stimulation is widely used in basic neuroscience and in a large range of clinical applications. However, the layer-specific effects of electric stimulation on LFPs remain unclear. To address this gap, we conducted laminar LFP recordings of the primary visual cortex in monkeys while presenting a flash visual stimulus. Simultaneously, we applied a low frequency sinusoidal current to the occipital lobe with offset frequency to the flash stimulus repetition rate. We analyzed the modulation of visual-evoked potentials with respect to the applied phase of the electric stimulation. Our results reveal that only the deeper layers, but not the superficial layers, show phase-dependent changes in LFP components with respect to the applied current. Employing a cortical column model, we demonstrate that these in vivo observations can be explained by phase-dependent changes in the driving force within neurons of deeper layers. Our findings offer crucial insight into the selective modulation of cortical layers through electric stimulation, thus advancing approaches for more targeted neuromodulation.

Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease.

To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. The OCTA data demonstrated a statistically significant difference (P<0.05) in macular retinal microvessel density between the two groups. Specifically, in the SRL and DRL analyses, the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group (P<0.05). Furthermore, using the hemispheric segmentation method, the ILD group showed notable reductions in SL, SR, and IL in the superficial retina (P<0.05), as well as marked decreases in SL and IR in the deep retina (P<0.05). Similarly, when employing the ETDRS method, the ILD group displayed substantial drops in superficial retinal S and I (P<0.05), along with notable reductions in deep retinal L, I, and R (P<0.05). In the central annuli segmentation method, the ILD group exhibited a significant decrease in the superficial retinal C2-4 region (P<0.05), whereas the deep retina showed a notable reduction in the C3-5 region (P<0.05). Additionally, there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR. Furthermore, there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI (P<0.001). Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group. Conversely, their fundus retinal microvascular density is significantly lower. Furthermore, CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group. The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases, thereby enhancing disease management.

Collagenising gastritis

It is a rare condition defined histologically by superficial subepithelial collagen layer. Collagenous gastritis occurs in bimodal age distribution both paediatric and adults.Sub epithelial collagen distribution favours the body or fundus in paediatric age group and antrum in adults. Now present a case of collagenising gastritis in 50 year male who presented with vomiting to medical gastroenterology department.

Laminar multi-contrast fMRI at 7T allows differentiation of neuronal excitation and inhibition underlying positive and negative BOLD responses

Abstract A major challenge for human neuroimaging using functional MRI is the differentiation of neuronal excitation and inhibition which may induce positive and negative BOLD responses. Here, we present an innovative multi-contrast laminar functional MRI technique that offers comprehensive and quantitative imaging of neurovascular (CBF, CBV, BOLD) and metabolic (CMRO2) responses across cortical layers at 7T. This technique was first validated through a finger-tapping experiment, revealing ‘double-peak’ laminar activation patterns within the primary motor cortex. By employing a ring-shaped visual stimulus that elicited positive and negative BOLD responses, we further observed distinct neurovascular and metabolic responses across cortical layers and eccentricities in the primary visual cortex. This suggests potential feedback inhibition of neuronal activities in both superficial and deep cortical layers underlying the negative BOLD signals in the fovea, and also illustrates the neuronal activities in visual areas adjacent to the activated eccentricities.

Physical attributes of the soil in an area under Forage Palm management in the Agreste of Alagoas

The objective was to evaluate soil density (Ds) and penetration resistance (RP) in an experimental area with forage palm management. The study was conducted in an experimental area belonging to the Federal University of Alagoas - Arapiraca Campus. To determine the Ds, undeformed samples were collected at three points within the plot, each point with three different depths (0-10; 10-20 and 20-30 cm). To determine the PR, the impact penetrometer was used at depths of 0-60 cm. For comparison purposes, samples were collected in a native forest area. The data were submitted to analysis through the statistical program R and Tukey test at 1 and 5% probability. Ds ranged from 1.59 to 1.63 g cm-3, not differing significantly. The lowest densities were obtained in the surface layer, influenced by the contribution of organic matter and greater presence of roots. In all depths evaluated, the Ds values were lower for the native forest area. In relation to PR, the values gradually increased up to the first 20 cm of depth for most treatments, reflecting the influence that the non-soil revolution causes in the most superficial layers. Therefore, Ds did not differ significantly. The 0-10 cm layer showed the lowest Ds values. The native forest showed the lowest Ds values at all depths when compared to the managed area. PR gradually increased to the first 20 cm of depth for most of the treatments analyzed.

Microbial imbalance in Darier disease: Dominance of various staphylococcal species and absence of Cutibacteria

Darier disease (DD) is a rare autosomal dominant genodermatosis characterized by erythematous papules and plaques mainly involving sebaceous areas, such as the face, chest and back. Skin microbiome plays an essential role in maintaining skin homeostasis. A disturbed skin microbiome may contribute to the exacerbation of DD. We investigated the bacterial composition of two predilectional sites in DD patients and healthy individuals. We also measured the microbiome composition of deeper skin layers, where diversity was significantly reduced compared to the superficial layer of the skin from the same area. The microbiome of DD patients at lesional sites differed from that of non-lesional skin areas; moreover, non-lesional sites were different from those of the controls. Lesional areas were dominated by Staphylococcus species, such as S. aureus, S. epidermidis, S. hominis, S. sciuri, and S. equorum. However, levels of Cutibacterium acnes (formerly Propionibacterium acnes) and C. acnes subspecies defendens were significantly lower in lesional sites than in non-lesional sites. A significant decrease was measured in the levels of these two bacteria between non-lesional and control samples. Our findings may indicate that alterations in the skin microbiome could contribute to the inflammation of skin lesions in DD.

Factors Associated with Retinal Microvasculature Dropout Induced by Elevation of Intraocular Pressure in Primary Open-Angle Glaucoma.

To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD). This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation. A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively. Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression. What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.

Layer-specific BOLD effects in gradient and spin-echo acquisitions in somatosensory cortex.

Previous studies have shown varied BOLD signals with gradient echo (GE) across cortical depth. To interpret these variations, and understand the effects of vascular geometry and size, the magnitudes and layer distributions of GE and spin-echo (SE) BOLD functional MRI signals were compared in the somatosensory cortex of squirrel monkeys during tactile stimulation and in a resting state at high spatial resolution and high field. A block-design stimulation was used to identify tactile-evoked activation signals in somatosensory Areas 3b and 1. Layer-specific connectivities were calculated using resting-state data. Signal power spectra were compared by depth and pulse sequence. The measured ratios of transverse relaxation rate changes were compared with Anderson and Weiss's model. SE signals showed a 26% lower percentage signal change during tactile stimulation compared with GE, along with a slower time course. SE signals remained consistent but weaker in lower layers, whereas GE signals decreased with cortical depth. This pattern extended to resting-state power spectra. Resting-state functional connectivity indicated larger connectivity between the top layers of Area 3b and Area 1 for GE, with minimal changes for SE. Comparisons with theory suggest vessel diameters ranging from 19.4 to 9 microns are responsible for BOLD effects across cortical layers at 9.4 T. These results provide further evidence that at high field, SE BOLD signals are relatively free of contributions from sources other than microvascular changes in response to neural activity, whereas GE signals, even in the superficial layers, are not dominated by very large vessels.

Propofol-mediated loss of consciousness disrupts predictive routing and local field phase modulation of neural activity

Predictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from the deep-layer cortex via alpha/beta (8 to 30 Hz) oscillations. They inhibit the gamma (40 to 100 Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in circuits unprepared by alpha/beta, resulting in enhanced gamma and spiking. To test the predictive routing model and its role in consciousness, we collected data from intracranial recordings of macaque monkeys during passive presentation of auditory oddballs before and after propofol-mediated loss of consciousness (LOC). In line with the predictive routing model, alpha/beta oscillations in the awake state served to inhibit the processing of predictable stimuli. Propofol-mediated LOC eliminated alpha/beta modulation by a predictable stimulus in the sensory cortex and alpha/beta coherence between sensory and frontal areas. As a result, oddball stimuli evoked enhanced gamma power, late period (>200 ms from stimulus onset) spiking, and superficial layer sinks in the sensory cortex. LOC also resulted in diminished decodability of pattern-level prediction error signals in the higher-order cortex. Therefore, the auditory cortex was in a disinhibited state during propofol-mediated LOC. However, despite these enhanced feedforward responses in the auditory cortex, there was a loss of differential spiking to oddballs in the higher-order cortex. This may be a consequence of a loss of within-area and interareal spike-field coupling in the alpha/beta and gamma frequency bands. These results provide strong constraints for current theories of consciousness.

Computed tomographic features of Morel-Lavallée lesions in 3 cats.

To describe the CT features of Morel-Lavallée lesions (MLLs) and their association with trauma in cats. This study aimed to investigate whether MLL fluid in cats accumulates between the dermis and deep fascia near superficial trauma, exhibits a vertical attenuation gradient, and shows no or only mild contrast enhancement on CT images. 3 young cats: a 1-year-old neutered male domestic shorthair cat, a 2-year-old neutered male domestic shorthair cat, and a 3-year-old neutered female British Shorthair cat. The clinical presentation of the 3 cats in the study involved recurrent swelling and fluid accumulation affecting at least 1 pelvic limb following trauma. In all cases, there was a fluid-filled space deep to the skin and superficial subcutaneous layer but superficial to the deep fascial plane overlying the muscular component of the pelvic limbs. The MLL fluid had a vertical attenuation gradient and no or only mild contrast enhancement. Morel-Lavallée lesions are often initially overlooked, likely due to distraction by concomitant significant bone injuries, and can be mistaken for hematomas, seromas, subcutaneous edema, contusions, or cellulitis, leading to less aggressive treatment. If left untreated, MLLs present a significant risk of extensive skin necrosis compared to other types of subcutaneous swelling.

Spatial context non-uniformly modulates inter-laminar information flow in the primary visual cortex.

Our visual experience is a result of the concerted activity of neuronal ensembles in the sensory hierarchy. Yet, how the spatial organization of objects influences this activity remains poorly understood. We investigate how inter-laminar information flow within the primary visual cortex (V1) is affected by visual stimuli in isolation or with flankers at spatial configurations that are known to cause non-uniform degradation of perception. By employing dimensionality reduction approaches to simultaneous, layer-specific population recordings, we establish that information propagation between cortical layers occurs along a structurally stable communication subspace. The spatial configuration of contextual stimuli differentially modulates inter-laminar communication efficacy, the balance of feedforward and effective feedback signaling, and contextual signaling in the superficial layers. Remarkably, these modulations mirror the spatially non-uniform aspects of perceptual degradation. Our results suggest a model of retinotopically non-uniform cortical connectivity in the output layers of V1 that influences information flow in the sensory hierarchy.

Involvement of a lateral entorhinal cortex engram in episodic-like memory recall

Episodic memory relies on the entorhinal cortex (EC), a crucial hub connecting the hippocampus and sensory processing regions. This study investigates the role of the lateral EC (LEC) in episodic-like memory in mice. Here, we employ the object-place-context-recognition task (OPCRT), a behavioral test used to study episodic-like memory in rodents. Electrophysiology in brain slices reveals that OPCRT specifically induces a shift in the threshold for the induction of synaptic plasticity in LEC superficial layer II. Additionally, a dual viral system is used to express chemogenetic receptors coupled to the c-Fos promoter in neurons recruited during the learning. We demonstrate that the inhibition of LEC neurons impairs the performance of the mice in the memory task, while their stimulation significantly facilitates memory recall. Our findings provide evidence for an episodic-like memory engram in the LEC and emphasize its role in memory processing within the broader network of episodic memory.

Pharmacological Impacts of Mucopolysacccharide Polyphosphates in the Epidermis Involves Inhibition of Amphiregulin-Mediated Signals in Keratinocytes.

The epidermis, the most superficial layer of the human skin, serves a critical barrier function, protecting the body from external pathogens and allergens. Dysregulation of epidermal differentiation contributes to barrier dysfunction and has been implicated in the pathology of various dermatological diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is a moisturising agent used to treat xerosis in patients with AD. However, its mechanism of action on keratinocytes, the main constituents of the epidermis, remains unclear. In this study, we investigated the effect of MPS on keratinocytes by subjecting adult human epidermal and three-dimensional cultured keratinocytes to MPS treatment, followed by transcriptome analysis. The analysis revealed that MPS treatment enhances keratinocyte differentiation and suppresses proliferation. We focused on amphiregulin (AREG), a membrane protein that belongs to the epidermal growth factor (EGF) family and possesses a heparin-binding domain, as a significant target among the genes altered by MPS. MPS exerted an inhibitory effect directly on AREG, rather than on EGF receptors or other members of the EGF family. Furthermore, AREG leads to a reduction in epidermal barrier function, whereas MPS contributes to barrier enhancement via AREG inhibition. Collectively, these findings suggest that MPS modulates barrier function through AREG inhibition, offering insights into potential therapeutic strategies for skin barrier restoration.