Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance.

Transient exposure to ketamine can trigger lasting changes in behavior and mood. We found that brief ketamine exposure causes long-term suppression of futility-induced passivity in larval zebrafish, reversing the "giving-up" response that normally occurs when swimming fails to cause forward movement. Whole-brain imaging revealed that ketamine hyperactivates the norepinephrine-astroglia circuit responsible for passivity.

Longitudinal changes in electrophysiology and widefield calcium imaging following electrode implantation.

. Intracortical microelectrode arrays often fail to deliver reliable signal quality over chronic recordings, and the effect of an implanted recording array on local neural circuits is not completely understood..

Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.

This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified , a highly brain penetrant and selective mGlu NAM which displayed moderate potency against both human and rat mGlu.

Mentalizing About Dynamic Social Action Sequences Is Supported by the Cerebellum, Basal Ganglia, and Neocortex: A Meta-Analysis of Activation and Connectivity.

The posterior cerebellum and anterior basal ganglia are critical subcortical structures for learning and identifying dynamic action sequences, in concert with the neocortex. The present analysis investigates the role of action sequences during social mentalizing, termed here dynamic or sequential social mentalizing. Although the role of the cerebellum in dynamic social mentalizing was extensively investigated during the last decade, the basal ganglia were long ignored.

Beyond-local neural information processing in neuronal networks.

While there is much knowledge about local neuronal circuitry, considerably less is known about how neuronal input is integrated and combined across neuronal networks to encode higher order brain functions. One challenge lies in the large number of complex neural interactions. Neural networks use oscillating activity for information exchange between distributed nodes.

The role of pain expectancy and its confidence in placebo hypoalgesia and nocebo hyperalgesia.

Placebo hypoalgesia and nocebo hyperalgesia, which exemplify the impact of expectations on pain, have recently been conceptualised as Bayesian inferential processes, yet empirical evidence remains limited. Here, we explore whether these phenomena can be unified within the same Bayesian framework by testing the predictive role of expectations and their level of precision (ie, expectation confidence) on pain, with both predictors measured at the metacognitive level. Sixty healthy volunteers underwent a pain test (ie, 8 noxious electrical stimuli) before (Baseline) and after (T0, T1, T2) receiving a sham treatment associated with hypoalgesic (placebo), hyperalgesic (nocebo), or neutral (control) verbal suggestions, depending on group allocation.

Early-life IL-4 administration induces long-term changes in microglia in the cerebellum and prefrontal cortex.

Microglia are crucial for brain development and their function can be impacted by postnatal insults, such as early-life allergies. These are characterized by an upregulation of interleukin (IL)-4 levels. Allergies share a strong comorbidity with Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD).

Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks.

The amygdala attributes valence and emotional salience to environmental stimuli and regulates how these stimuli affect behavior. Within the amygdala, a distinct class of evolutionarily conserved neurons form the intercalated cell (ITC) clusters, mainly located around the boundaries of the lateral and basal nuclei. Here, we review the anatomical, physiological and molecular characteristics of ITCs, and detail the organization of ITC clusters and their connectivity with one another and other brain regions.

Development and function of the medial amygdala.

Across studied vertebrates, the medial amygdala (MeA) is a central hub for relaying sensory information with social and/or survival relevance to downstream nuclei such as the bed nucleus of stria terminalis (BNST) and the hypothalamus. MeA-driven behaviors, such as mating, aggression, parenting, and predator avoidance are processed by different molecularly defined inhibitory and excitatory neuronal output populations. Work over the past two decades has deciphered how diverse MeA neurons arise from embryonic development, revealing contributions from multiple telencephalic and diencephalic progenitor domains.

A Bibliometric Analysis of Macrophage Research Associated with Periodontitis Over the Past Two Decades.

Macrophages are vital for regulating periodontal health, and numerous studies have extensively investigated their role in periodontitis progression. This study employs bibliometric analysis to identify research trends and hotspots related to macrophages in periodontitis from 2004 to 2024, thereby guiding future investigations and exploring potential clinical applications. Literature retrieval and dataset export were conducted via the Web of Science Core Collection database.

Nerve-Mimetic Adhesive Hydrogel Electroceuticals: Tailoring In Situ Physically Entangled Domains in Singular Polymers.

Implantable electrochemicals stand out as promising candidates for resolving peripheral nerve injuries. However, challenges persist in designing bioelectronic materials that mimic tissue due to modulus matching, conformal adhesion, and immune responses. Herein, we present a nerve-mimicking design rationale for biocompatible hydrogel-based electroceuticals with a tissue-like modulus, robust and conformal tissue adhesion, exceptional mechanical toughness, and efficient stress dissipation.

Self-reported Dizziness, Postural Stability, and Sensory Integration After Mild Traumatic Brain Injury: A Naturalistic Follow-up Study.

Objective: The aim of the study is to evaluate changes in dizziness, postural stability, and sensory integration after mild traumatic brain injury over a 12-wk period.

Methods: One hundred adults with mild traumatic brain injury were analyzed. The Dizziness Handicap Inventory questionnaire was used for subjective evaluations.

Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex.

Neural stem cells (NSCs) can give rise to both neurons and glia, but the regulatory mechanisms governing their differentiation transitions remain incompletely understood. Here, we address the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stages of dorsal cortical development. We find that the CDKIs p18 and p27 are upregulated at the onset of astrocyte generation.

I am where I believe my body is: The interplay between body spatial prediction and body ownership.

Body ownership refers to the feeling that the body belongs to oneself. This study explores how our ability to predict our body's location in space influences feelings of ownership and disownership towards it, comparing two illusion techniques: the virtual Rubber Hand Illusion (vRHI) and the first-person perspective Full-Body Illusion (1pp-FBI). Participants were exposed to each illusion, where they observed a virtual body aligned or misaligned with their own.

Behind the scenes: exploring neurological journal editors' work habits, decisions, and potential sources of conflict of interest.

Background And Objectives: Editors of scientific journals play a key role in the health-related research process. Our study aims to characterize the demographics, work habits, decision-making processes, and ethical challenges faced by editors of neurological journals and to evaluate associations between editor or journal characteristics and editorial decisions, as well as sources of conflict of interest.

Methods: Cross-sectional study involving editors from neurological journals that fell above the 50th percentile in the Scimago rankings.

Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.

Introduction: Knowledge about the distribution and frequency of the respective haplotypes on the wildtype and mutant allele is highly relevant in the context of future gene therapy clinical studies in Spinocerebellar Ataxia Type 3, the most common autosomal dominantly inherited ataxia. Single nucleotide polymorphisms associated to the disease-causing gene, ATXN3, have been determined. We wanted to investigate the frequency and regional distribution of two intragenic single nucleotide polymorphisms (SNPs) in a large European SCA3 cohort and their relation to the clinical phenotype.

Discovery of VU6024578/BI02982816: An mGlu Positive Allosteric Modulator with Efficacy in Preclinical Antipsychotic and Cognition Models.

Herein, we report progress toward a metabotropic glutamate receptor subtype 1 (mGlu) positive allosteric modulator (PAM) clinical candidate and the discovery of VU6024578/BI02982816. From a weak high-throughput screening hit (VU0538160, EC > 10 μM, 71% Glu), optimization efforts improved functional potency over 185-fold to deliver the selective (inactive on mGlu) and CNS penetrant (rat K = 0.99, K = 0.

Microglia as hunters or gatherers of brain synapses.

Over a decade ago, it was discovered that microglia, the brain's immune cells, engulf synaptic material in a process named microglial pruning. This term suggests that microglia actively sculpt brain circuits by tagging and phagocytosing unwanted synapses. However, live imaging studies have yet to demonstrate how microglial synapse elimination occurs.

Environmental enrichment-induced cognitive recovery after a moderate pediatric traumatic brain injury is associated with the gut microbiota and neuroinflammation.

Pediatric traumatic brain injury (TBI) is a significant health concern, yet access to rehabilitation therapies for children remains limited. Environmental enrichment (EE) is a preclinical model of neurorehabilitation that promotes behavioral recovery and reduces neuroinflammation after TBI. While the gut microbiota has recently emerged as a potential therapeutic target for treating TBI sequelae in adults, its role in recovery after pediatric TBI remains unclear.

Preventive effect of MitoQ supplementation and endurance training on glioblastoma and its consequences: TLR4/CREB/ NF-κβ /IL-1β pathway and behaviors.

Objective: The present study investigated the preventive effect of MitoQ supplementation and endurance training (ET) on the TLR4/CREB/ NF-κβ signaling pathway, antioxidant indices, and behaviors in C6-induced glioblastoma (GBM) in rats.

Methods: 60 male Wistar rats were randomly divided into five groups (n = 12); Sham, Tumor, MitoQ, ET, and MitoQ + ET. Rats in the training groups performed endurance training (5 days per week), and MitoQ at the dose of 250 µM/L daily was administered in drinking water for 8 weeks.

Discovery of VU0467319: an M Positive Allosteric Modulator Candidate That Advanced into Clinical Trials.

Herein we detail the of VU0467319 (VU319), an M Positive Allosteric Modulator (PAM) clinical candidate that successfully completed a Phase I Single Ascending Dose (SAD) clinical trial. VU319 () is a moderately potent M PAM (M PAM EC = 492 nM ± 2.9 nM, 71.

An atomic look at the interface of GHSR and its partners.

G protein-coupled receptors (GPCRs) regulate cellular activity by transducing external signals and selectively coupling them to intracellular partners. Ghrelin receptor (GHSR) has garnered significant interest over the past decade owing to its diverse functional roles. In this study, we simulated five distinct GHSR-partner complexes, including G, G, and arrestin in two conformational states, to investigate the structural determinants of partner coupling.

Microglial lipid phosphatase SHIP1 limits complement-mediated synaptic pruning in the healthy developing hippocampus.

The gene inositol polyphosphate-5-phosphatase D (INPP5D), which encodes the lipid phosphatase SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1), is associated with the risk of Alzheimer's disease (AD). How it influences microglial function and brain physiology is unclear. Here, we showed that SHIP1 was enriched in early stages of healthy brain development.

Neurorights Training of a Multidisciplinary Studentship Based on Realistic Neuroscience.

As is usually the case with other topics addressed by neuroethics, a rigorous analysis of neurorights requires an interdisciplinary approach. In response to this need and in the context of the global expansion of regulatory initiatives on neurorights, we coordinated, under the auspices of the International Center for Neuroscience and Ethics (CINET), an introductory course on neurorights from a neuroscientific perspective. The course, aimed at sixty students from diverse backgrounds (neuroscience, psychology, and law, among others), consisted of a 10-hr training that showed the current approaches and discussions on neurorights and outlined cutting-edge technologies to register, analyze, and manipulate human brain activity from a realistic stance.