The flow of reward information through neuronal ensembles in the accumbens.

The nucleus accumbens shell (NAcSh) integrates reward information through diverse and specialized neuronal ensembles, influencing decision-making. By training rats in a probabilistic choice task and recording NAcSh neuronal activity, we found that rats adapt their choices based solely on the presence or absence of a sucrose reward, suggesting they build an internal representation of reward likelihood. We further demonstrate that NAcSh ensembles dynamically process different aspects of reward-guided behavior, with changes in composition and functional connections observed throughout the reinforcement learning process. The NAcSh forms a highly connected network characterized by a heavy-tailed distribution and the presence of neuronal hubs, facilitating efficient information flow. Reward delivery enhances mutual information, indicating increased communication between ensembles and network synchronization, whereas reward omission decreases it. Our findings reveal how reward information flows through dynamic NAcSh ensembles, whose flexible membership adapts as the rat learns to obtain rewards (energy) in an ever-changing environment.

Behavioral Changes and Long-Term Cortical Thickness Alterations in Women with Fibromyalgia.

OBJECTIVES: The purpose of this study was to examine long-term brain and behavioral changes in patients with fibromyalgia (FM) compared to healthy individuals. METHODS: Data from 33 female volunteers with FM and 33 healthy controls women paired by age and school degree were used to analyze the cortical thickness from high-resolution T1-weighted magnetic resonance imaging (MRI) obtained through a 3T-MRI scanner. Additionally, the Toronto Alexithymia Scale, the Positive and Negative Affect Scale, the emotion regulation questionnaire (ERQ), and the Hamilton Depression and Anxiety rating scales were used to evaluate the behavioral changes. RESULTS: The findings indicate significant cortical structure differences in the right cerebral hemisphere between groups in the insular anterior cortex precentral and postcentral gyrus (P < .001). The FM group scored higher for alexithymia (P < .01), negative affect (P < .01), anxiety (P < .01), and depression (P < .01) symptoms, on the other hand, scored lower for positive affect (P < .01). No differences were found on the left cerebral hemisphere. Furthermore, there was a negative correlation between the right insular anterior cortex and Toronto Alexithymia Scale (P < .001). CONCLUSION: This study showed long-term brain and behavioral changes in patients with FM, suggesting notable neurophysiological alterations associated with this chronic pain condition. It provides new insights into how FM may affect brain health and potential biomarkers for the condition.

Unveiling differential gene co-expression networks and its effects on levodopa-induced dyskinesia.

Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson's disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain.

White matter structural bases for phase accuracy during tapping synchronization.

We determined the intersubject association between the rhythmic entrainment abilities of human subjects during a synchronization-continuation tapping task (SCT) and the macro- and microstructural properties of their superficial (SWM) and deep (DWM) white matter. Diffusion-weighted images were obtained from 32 subjects who performed the SCT with auditory or visual metronomes and five tempos ranging from 550 to 950 ms. We developed a method to determine the density of short-range fibers that run underneath the cortical mantle, interconnecting nearby cortical regions (U-fibers). Notably, individual differences in the density of U-fibers in the right audiomotor system were correlated with the degree of phase accuracy between the stimuli and taps across subjects. These correlations were specific to the synchronization epoch with auditory metronomes and tempos around 1.5 Hz. In addition, a significant association was found between phase accuracy and the density and bundle diameter of the corpus callosum (CC), forming an interval-selective map where short and long intervals were behaviorally correlated with the anterior and posterior portions of the CC. These findings suggest that the structural properties of the SWM and DWM in the audiomotor system support the tapping synchronization abilities of subjects, as cortical U-fiber density is linked to the preferred tapping tempo and the bundle properties of the CC define an interval-selective topography.

Circulating platelets modulate oligodendrocyte progenitor cell differentiation during remyelination.

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.

Twelve tips for starting and organizing a local Brain Bee anywhere.

The Brain Bee serves as an international platform providing high school students with opportunities for undergraduate and graduate-level education in neuroscience. This annual competition welcomes participation from high school students and schools, fostering both individual- and team-based competition in a dynamic and engaging manner. The assessment involves a primary multiple-choice and short-answer exam, a secondary neuroanatomical lab practical exam, and a final oral exam administered by affiliated faculty or coordinators. During the final oral exam, the top ten students are given three chances and simultaneously respond to the same question. They write their answers on individual whiteboards until only one student remains. This unique format not only adds an element of excitement, but also allows students to build confidence within themselves and connections within STEM fields. The importance of local Brain Bees is emphasized as winners from these chapters earn the opportunity to compete nationally, and potentially internationally. Throughout the academic year, local Brain Bees, led by college students and faculty, educate high school students about various neuroscientific fields and their STEM applications through interactive and engaging sessions. These sessions culminate in an annual competition where students explore the intricacies of the human brain, spanning human physiology, pathology, and behavior. The program also exposes students to anatomical models, research, and guest speakers within the field of neuroscience. To ensure the success and continuity of local chapters, our 12-tips article provides valuable advice for running a safe and smoothly operating Brain Bee program, promoting sustained participation and enthusiasm.

Astrocytes in Pain Perception: A Systems Neuroscience Approach.

Astrocytes play an active role in the function of the brain integrating neuronal activity and regulating back neuronal dynamic. They have recently emerged as active contributors of brain's emergent properties such as perceptions. Here, we analyzed the role of astrocytes in pain perception from the lens of systems neuroscience, and we do this by analyzing how astrocytes encode nociceptive information within brain processing areas and how they are key regulators of the internal state that determines pain perception. Specifically, we discuss the dynamic interactions between astrocytes and neuromodulators, such as noradrenaline, highlighting their role in shaping the level of activation of the neuronal ensemble, thereby influencing the experience of pain. Also, we will discuss the possible implications of an "Astro-NeuroMatrix" in the integration of pain across sensory, affective, and cognitive dimensions of pain perception.

Impact of aging on the GABAB receptor-mediated connectome.

GABA B receptors (GABABRs) are heterodimeric seven-transmembrane receptors that interact with a range of proteins and form large protein complexes on cholesterol-rich membrane microdomains. As the brain ages, membrane cholesterol levels exhibit alterations, although it remains unclear how these changes impact protein-protein interactions and downstream signaling. Herein, we studied the structural bases for the interaction between GABABR and the KCC2 transporter, including their protein expression and distribution, and we compared data between young and aged rat cerebella. Also, we analyzed lipid profiles for both groups, and we used molecular dynamics simulations on three plasma membrane systems with different cholesterol concentrations, to further explore the GABABR-transporter interaction. Based on our results, we report that a significant decrease in GABAB2 subunit expression occurs in the aged rat cerebella. After performing a comparative co-immunoprecipitation analysis, we confirm that GABABR and KCC2 form a protein complex in adult and aged rat cerebella, although their interaction levels are reduced substantially as the cerebellum ages. On the other hand, our lipid analyses reveal a significant increase in cholesterol and sphingomyelin levels of the aged cerebella. Finally, we used the Martini coarse-grained model to conduct molecular dynamics simulations, from which we observed that membrane cholesterol concentrations can dictate whether the GABABR tail domains physically establish G protein-independent contacts with a transporter, and the timing when those associations eventually occur. Taken together, our findings illustrate how age-related alterations in membrane cholesterol levels affect protein-protein interactions, and how they could play a crucial role in regulating GABABR's interactome-mediated signaling. Significance Statement: This study elucidates age-related changes in cerebellar GABAB receptors (GABABRs), KCC2, and plasma membrane lipids, shedding light on mechanisms underlying neurological decline. Molecular dynamics simulations reveal how membrane lipids influence protein-protein interactions, offering insights into age-related neurodegeneration. The findings underscore the broader impact of cerebellar aging on motor functions, cognition, and emotional processing in the elderly. By elucidating plasma membrane regulation and GABAergic dynamics, this research lays the groundwork for understanding aging-related neurological disorders and inspires further investigation into therapeutic interventions.

Immunosuppression-induced Zika virus reactivation causes brain inflammation and behavioral deficits in mice.

Zika virus (ZIKV) is a neurotropic flavivirus that can persist in several tissues. The late consequences of ZIKV persistence and whether new rounds of active replication can occur, remain unaddressed. Here, we investigated whether neonatally ZIKV-infected mice are susceptible to viral reactivation in adulthood. We found that when ZIKV-infected mice are treated with immunosuppressant drugs, they present increased susceptibility to chemically induced seizures. Levels of subgenomic flavivirus RNAs (sfRNAs) were increased, relative to the amounts of genomic RNAs, in the brains of mice following immunosuppression and were associated with changes in cytokine expression. We investigated the impact of immunosuppression on the testicles and found that ZIKV genomic RNA levels are increased in mice following immunosuppression, which also caused significant testicular damage. These findings suggest that ZIKV can establish new rounds of active replication long after acute stages of disease, so exposed patients should be monitored to ensure complete viral eradication.

Understanding the effects of omega-3 fatty acid supplementation on the physical properties of brain lipid membranes.

A deficiency in omega-3 fatty acids (ω3 FAs) in the brain has been correlated with cognitive impairment, learning deficiencies, and behavioral changes. In this study, we provided ω3 FAs as a supplement to spontaneously hypertensive rats (SHR+ ω3). Our focus was on examining the impact of dietary supplementation on the physicochemical properties of the brain-cell membranes. Significant increases in ω3 levels in the cerebral cortex of SHR+ ω3 were observed, leading to alterations in brain lipid membranes molecular packing, elasticity, and lipid miscibility, resulting in an augmented phase disparity. Results from synthetic lipid mixtures confirmed the disordering effect introduced by ω3 lipids, showing its consequences on the hydration levels of the monolayers and the organization of the membrane domains. These findings suggest that dietary ω3 FAs influence the organization of brain membranes, providing insight into a potential mechanism for the broad effects of dietary fat on brain health and disease.

Applied human neuroscience: Fostering and designing inclusive environments with the 3E-Cognition perspective.

The conventional medical paradigm often focuses on deficits and impairments, failing to capture the rich tapestry of experiences and abilities inherent in neurodiversity conditions. In this article, we introduce the 3E-Cognition perspective, offering a paradigm shift by emphasizing the dynamic interplay between the brain, body, and environment in shaping cognitive processes. The perspective fosters a more inclusive and supportive understanding of neurodiversity, with potential applications across various domains such as education, workplace, and healthcare. We begin by introducing the 3E-Cognition principles: embodied, environmentally scaffolded, and enactive. Then, we explore how the 3E-Cognition perspective can be applied to create inclusive environments and experiences for neurodiverse individuals. We provide examples in the realms of education, workplace, and healthcare. In all of these domains, spaces, methodologies, epistemologies, and roles that cater to diverse needs and strengths can be designed using the 3E principles. Finally, we discuss the challenges and benefits of implementing the 3E-Cognition perspective. We focus on the need for technological advancements and research in complex real-world scenarios; we suggest mobile brain/body imaging is a possible solution. We furthermore highlight the importance of recognizing and valuing the diverse manners of experiencing and interacting with the world, the promotion of diverse well-being, and the facilitation of innovation and creativity. Thus, we conclude that the 3E-Cognition perspective offers a groundbreaking approach to understanding and supporting neurodiversity: by embracing the inherent interconnectedness of the brain, body, and environment, we can create a more inclusive and supportive world.

Computational Tools for Neuronal Morphometric Analysis: A Systematic Search and Review.

Morphometry is fundamental for studying and correlating neuronal morphology with brain functions. With increasing computational power, it is possible to extract morphometric characteristics automatically, including features such as length, volume, and number of neuron branches. However, to the best of our knowledge, there is no mapping of morphometric tools yet. In this context, we conducted a systematic search and review to identify and analyze tools within the scope of neuron analysis. Thus, the work followed a well-defined protocol and sought to answer the following research questions: What open-source tools are available for neuronal morphometric analysis? What morphometric characteristics are extracted by these tools? For this, aiming for greater robustness and coverage, the study was based on the paper analysis as well as the study of documentation and tests with the tools available in repositories. We analyzed 1,586 papers and mapped 23 tools, where NeuroM, L-Measure, and NeuroMorphoVis extract the most features. Furthermore, we contribute to the body of knowledge with the unprecedented presentation of 150 unique morphometric features whose terminologies were categorized and standardized. Overall, the study contributes to advancing the understanding of the complex mechanisms underlying the brain.

Effectiveness of in-group versus individually administered pain neuroscience education on clinical and psychosocial outcomes in patients with chronic low back pain: randomized controlled study protocol.

Objective: (1) This trial will compare the clinical and psychosocial effectiveness of in-group and individually pain neuroscience education (PNE) in patients with chronic low back pain (CLBP). In addition, (2) the influence of social determinants of health on post-treatment results will be analyzed. Methods: A three-arm randomized controlled trial will be conducted. Sixty-nine participants with CLBP will be recruited in a 1:1:1 ratio. Participants, assessor, and statistician will be blinded to group assignment. The PNE intervention will be adapted to the context of the participants. An experimental group (n = 33) will receive PNE in an in-group modality, the other experimental group (n = 33) will receive PNE in an individually modality and the control group (n = 33) will continue with usual care. Additionally, participants will be encouraged to stay active by walking for 20-30 min 3-5 times per week and will be taught an exercise to improve transversus abdominis activation (bracing or abdominal following). The outcome measures will be fear avoidance and beliefs, pressure pain threshold, pain self-efficacy, catastrophizing, pain intensity, and treatment expectation. Outcome measures will be collected at one-week before intervention, immediately post-intervention, and four-weeks post-intervention. Conclusion: The innovative approach of PNE oriented to fear beliefs proposed in this study could broaden the application strategies of this educational therapeutic modality. Impact. Contextualized PNE delivered by physical therapist could be essential to achieve a good cost-effectiveness ratio of this intervention to improve the clinical condition of people with CLBP.

Sleep-dependent decorrelation of hippocampal spatial representations.

Neuronal ensembles are crucial for episodic memory and spatial mapping. Sleep, particularly non-REM (NREM), is vital for memory consolidation, as it triggers plasticity mechanisms through brain oscillations that reactivate neuronal ensembles. Here, we assessed their role in consolidating hippocampal spatial representations during sleep. We recorded hippocampus activity in rats performing a spatial object-place recognition (OPR) memory task, during encoding and retrieval periods, separated by intervening sleep. Successful OPR retrieval correlated with NREM duration, during which cortical oscillations decreased in power and density as well as neuronal spiking, suggesting global downregulation of network excitability. However, neurons encoding specific spatial locations (i.e., place cells) or objects during OPR showed stronger synchrony with brain oscillations compared to non-encoding neurons, and the stability of spatial representations decreased proportionally with NREM duration. Our findings suggest that NREM sleep may promote flexible remapping in hippocampal ensembles, potentially aiding memory consolidation and adaptation to novel spatial contexts.

Exploring undiscovered public knowledge in neuroscience.

In this essay, I argue that the combination of research synthesis and philosophical methods can fill an important methodological gap in neuroscience. While experimental research and formal modelling have seen their methods progressively increase in rigour and sophistication over the years, the task of analysing and synthesizing the vast literature reporting new results and models has lagged behind. The problem is aggravated because neuroscience has grown and expanded into a vast mosaic of related but partially independent subfields, each with their own literatures. This fragmentation not only makes it difficult to see the full picture emerging from neuroscience research but also limits progress in individual subfields. The current neuroscience literature has the perfect conditions to create what the information scientist Don Swanson called "undiscovered public knowledge"-knowledge that exists in the mutual implications of different published pieces of information but that is nonetheless undiscovered because those pieces have not been explicitly connected. Current methods for rigorous research synthesis, such as systematic reviews and meta-analyses, mostly focus on combining similar studies and are not suited for exploring undiscovered public knowledge. To that aim, they need to be adapted and supplemented. I argue that successful exploration of the hidden implications in the neuroscience literature will require the combination of these adapted research synthesis methods with philosophical methods for rigorous (and creative) analysis and synthesis.

Non-canonical type 1 cannabinoid receptor signaling regulates night visual processing in the inner rat retina.

Type 1 cannabinoid receptors (CB1Rs) are expressed in major retinal neurons within the rod-pathway suggesting a role in regulating night visual processing, but the underlying mechanisms remain poorly understood. Using acute rat retinal slices, we show that CB1R activation reduces glutamate release from rod bipolar cell (RBC) axon terminals onto AII and A17 amacrine cells through a pathway that requires exchange proteins directly activated by cAMP (EPAC1/2) signaling. Consequently, CB1R activation abrogates reciprocal GABAergic feedback inhibition from A17 amacrine cells. Moreover, the activation of CB1Rs in vivo enhances and prolongs the time course of the dim-light rod-driven visual responses, an effect that was eliminated when both GABAA and GABAC receptors were blocked. Altogether, our findings underscore a non-canonical mechanism by which cannabinoid signaling regulates RBC dyad synapses in the inner retina to regulate dim-light visual responses to fine-tune night vision.

Navigating the complex terrain of motivated behavior: a bibliometric and neuroscientific perspective.

Over several decades, motivated behavior has emerged as a crucial study area within neuroscience. Understanding the neural substrates and mechanisms driving behaviors related to reward, addiction, and other motivation forms is pivotal for novel therapeutic interventions. This review provides a bibliometric analysis of the literature, highlighting the main trends, influential authors, and the potential future direction of the field. Utilizing a dataset comprised by 3,150 publications from the Web of Science and Scopus databases ("motivated behavior as query), we delve into key metrics like publication trends, keyword prevalence, author collaborations, citation impacts, and employed an unsupervised natural language processing technique - Latent Dirichlet Allocation - for topic modeling. From early investigations focusing on basic neural mechanism and behaviors in animal models to more recent studies exploring the complex interplay of neurobiological, psychological, and social factors in humans, the field had undergone a remarkable transformation. The last century has seen a proliferation of research dedicated to uncovering the intricacies of motivation, significantly enriching our understanding of its myriad implications for human behavior and mental health. This bibliometric analysis aims to offer comprehensive insights into this dynamic research area, highlighting the field's key contributions and potential future directions, thereby serving as a valuable resource for researchers, and hopefully give a more thorough understanding of the research area.