A genetically tractable jellyfish model for systems and evolutionary neuroscience.

Jellyfish are radially symmetric organisms without a brain that arose more than 500 million years ago. They achieve organismal behaviors through coordinated interactions between autonomously functioning body parts. Jellyfish neurons have been studied electrophysiologically, but not at the systems level. We introduce Clytia hemisphaerica as a transparent, genetically tractable jellyfish model for systems and evolutionary neuroscience. We generate stable F1 transgenic lines for cell-type-specific conditional ablation and whole-organism GCaMP imaging. Using these tools and computational analyses, we find that an apparently diffuse network of RFamide-expressing umbrellar neurons is functionally subdivided into a series of spatially localized subassemblies whose synchronous activation controls directional food transfer from the tentacles to the mouth. These data reveal an unanticipated degree of structured neural organization in this species. Clytia affords a platform for systems-level studies of neural function, behavior, and evolution within a clade of marine organisms with growing ecological and economic importance.

Does combining oro-facial manual therapy with bruxism neuroscience education affect pain and function in cases of awake bruxism? A pilot study.

BACKGROUND: Although awake bruxism is associated with temporomandibular disorder (TMD) as well as head and neck pain, the effects of physical therapy and bruxism education to address these factors have not been investigated. OBJECTIVE: The aim of this study was to evaluate the effects of oro-facial manual therapy and bruxism neuroscience education (BNE) on awake bruxism over a 3-week period with an open-ended follow-up questionnaire after 3 months. METHODS: Subjects (n = 28) were randomly allocated to one of two groups, an intervention group and a control group. Data regarding disability, function and pain were collected pre- and post-assessment, with all measures administered in a single-blind fashion. Participants in both groups received six treatment sessions during this period. In addition to manual therapy, participants were provided with information on the neurophysiological mechanisms of bruxism and contributing factors. Individual behavioural guidelines and daily exercises were determined in consultation with the therapist. An introduction to a bruxism specific app (Brux.App) was also provided, which all participants used as an adjunct to their treatment. RESULTS: The intervention group demonstrated notable improvement as indicated by their scores in the Neck Disability Index (NDI) (p = .008), Pain Disability Index (PDI) (p = .007) and Jaw Disability List (JDL) (p = .03). Furthermore, clinical assessments of the temporomandibular joint (TMJ) revealed a significant progress in terms of mouth opening (p = .03) and lateral jaw movement (laterotrusion) (p = .03). The mechanical pain threshold (PTT) of both the masseter (p = .02) and temporalis muscle (p = .05) also showed significant improvement. At 3-month follow-up, the questionnaire revealed that the majority of the intervention group (13/15, 87%) reported a benefit from the treatment. CONCLUSION: The reduction in pain and disability together with improvement in function and increased coping suggest a potential modification of awake bruxism through specialised musculoskeletal intervention and BNE tailored to the individual patient.

Ten simple rules for creating a brand-new virtual academic meeting (even amid a pandemic).

The increased democratization of the creation, implementation, and attendance of academic conferences has been a serendipitous benefit of the movement toward virtual meetings. The Coronavirus Disease 2019 (COVID-19) pandemic has accelerated the transition to online conferences and, in parallel, their democratization, by necessity. This manifests not just in the mitigation of barriers to attending traditional physical conferences but also in the presentation of new, and more importantly attainable, opportunities for young scientists to carve out a niche in the landscape of academic meetings. Here, we describe an early "proof of principle" of this democratizing power via our experience organizing the Canadian Computational Neuroscience Spotlight (CCNS; crowdcast.io/e/CCNS), a free 2-day virtual meeting that was built entirely amid the pandemic using only virtual tools. While our experience was unique considering the obstacles faced in creating a conference during a pandemic, this was not the only factor differentiating both our experience and the resulting meeting from other contemporary online conferences. Specifically, CCNS was crafted entirely by early career researchers (ECRs) without any sponsors or partners, advertised primarily using social media and "word of mouth," and designed specifically to highlight and engage trainees. From this experience, we have distilled "10 simple rules" as a blueprint for the design of new virtual academic meetings, especially in the absence of institutional support or partnerships, in this unprecedented environment. By highlighting the lessons learned in implementing our meeting under these arduous circumstances, we hope to encourage other young scientists to embrace this challenge, which would serve as a critical next step in further democratizing academic meetings.

The Effect of Pain Neuroscience Education on Sports Therapy and Rehabilitation Students' Knowledge, Attitudes, and Clinical Recommendations Toward Athletes With Chronic Pain.

Context: Pain education is a fundamental part of a holistic approach to athlete injury management. Objective: To investigate the effect of pain neuroscience education (PNE) on sports therapy and rehabilitation students (1) knowledge of persistent pain, (2) attitudes toward athletes with persistent pain, and (3) clinical recommendations for athletes with persistent pain. Design: Parallel groups, single-blind randomized control trial. Setting: A university in the United Kingdom. Participants: Sixty-one undergraduate and postgraduate sports therapy and rehabilitation students. Interventions: The PNE session (intervention group) provided detailed information on the neuroscience of persistent pain, the modulating role of psychosocial factors on pain biology, and how this information could be used to inform clinical practice. The red flags (control group) session provided information on screening patients with persistent pain for serious/sinister pathologies. Each education session lasted 70 minutes. Outcome measures: (1) Knowledge-the Revised Pain Neurophysiology Questionnaire; (2) Attitudes-the Health Care Pain Attitudes and Impairment Relationship Scale; and (3) Clinical recommendations-an athlete case vignette. Results: Posteducation, the PNE group had a greater increase in pain neuroscience knowledge (mean difference 3.2; 95% confidence interval [95% CI], 2.1 to 4.3; P < .01) and improved attitudes (mean difference -10.1; 95% CI, -16.6 to -3.6; P < .01). In addition, students in the PNE group were more likely to make appropriate clinical recommendations (odds ratio [OR]; 95% CI) regarding return-to-work (OR = 6.1; 95% CI, 1.1 to 32.3; P = .03), exercise (OR = 10.7; 95% CI, 2.6 to 43.7; P ≤ 01), and bed rest (OR = 4.3; 95% CI, 1.5 to 12.8; P = 01). Conclusion: A brief PNE session can, in the immediate term, increase sports therapy and rehabilitation students' knowledge of pain neuroscience, improve attitudes toward athletes with pain, and shift their clinical recommendations in line with current guidelines. Such changes could lead to enhanced rehabilitation for athletes with persistent pain.

Copy, edit, and paste: natural product approaches to biomaterials and neuroengineering.

Progress in the chemical sciences has formed the world we live in, both on a macroscopic and on a nanoscopic scale. The last century witnessed the development of high performance materials that interact with humans on many layers, from clothing to construction, from media to medical devices. On a molecular level, natural products and their derivatives influence many biological processes, and these compounds have enormously contributed to the health and quality of living of humans. Although coatings of stone materials with oils or resins (containing natural products) have led to improved tools already millennia ago, in contrast today, natural product approaches to designer materials, that is, combining the best of both worlds, remain scarce. In this Account, we will summarize our recent research efforts directed to the generation of natural product functionalized materials, exploiting the strategy of "copy, edit, and paste with natural products". Natural products embody the wisdom of evolution, and only total synthesis is able to unlock the secrets enshrined in their molecular structure. We employ total synthesis ("copy") as a scientific approach to address problems related to molecular structure, the biosynthesis of natural products, and their bioactivity. Additionally, the fundamental desire to investigate the mechanism of action of natural products constitutes a key driver for scientific inquiry. In an emerging area of relevance to society, we have prepared natural products such as militarinone D that can stimulate neurite outgrowth and facilitate nerve regeneration. This knowledge obtained by synthetic organic chemistry on complex natural products can then be used to design structurally simplified compounds that retain the biological power of the parent natural product ("edit"). This process, sometimes referred to as function-oriented synthesis, allows obtaining derivatives with better properties, improving their chemical tractability and reducing the step count of the synthesis. Along these lines, we have demonstrated that militarinone D can be truncated to yield structurally simplified analogs with improved activity. Finally, with the goal of designing bioactive materials, we have immobilized functionally optimized, neuritogenic natural products ("paste"). These materials could facilitate nerve regeneration, act as nerve guidance conduits, or lead to new approaches in neuroengineering. Based on the surface-adhesive properties of electron-deficient catecholates and the knowledge gathered on neuritogenic natural product derivatives, two mechanistically different design principles have been applied to generate neuritogenic materials. In conclusion, natural products, and their functionally optimized analogs, present a large, mostly untapped reservoir of powerful modulators of biological systems, and their hybridization with materials can lead to new approaches in various fields, from biofilm prevention to neuroengineering.

Bioactive marine drugs and marine biomaterials for brain diseases.

Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted.

The enigma of sleep: Implications of sleep neuroscience for the dental clinician and patient.

BACKGROUND: Sleep disturbances have been shown to result in considerable morbidity and mortality. It is important for dental clinicians to understand the neuroscience behind sleep disorders. TYPES OF STUDIES REVIEWED: The authors conducted a search of the literature published from January 1990 through March 2024 of sleep medicine-related articles, with a focus on neuroscience. The authors prioritized articles about the science of sleep as related to dental medicine. RESULTS: The authors found a proliferation of articles related to sleep neuroscience along with its implications in dental medicine. The authors also found that the intricate neuroscientific principles of sleep medicine are being investigated robustly. The salient features of, and the differences between, central and obstructive sleep apneas have been elucidated. Sleep genes, such as CRY, PER1, PER2, and CLOCK, and their relationship to cancer and neurodegeneration are also additions to this rapidly developing science. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The dental clinician has the potential to be the first to screen patients for possible sleep disorders and make prompt referrals to the appropriate medical professionals. This can be lifesaving as well as minimize potential future morbidity for the patient.

Temporomandibular Joint Disorder: An integrated study of the pathophysiology, neural mechanisms, and therapeutic strategies.

OBJECTIVE: The study aims to investigate Temporomandibular Joint Disorder (TMJD) through a interdisciplinary lens, integrating insights from neuroscience, dentistry, and psychology to dissect its complex pathophysiology and neural mechanisms. It focuses on exploring the neurobiological underpinnings of TMJD, emphasizing the role of pain perception, modulation, and the impact of neurophysiological changes on the disorder. DESIGN: This is a comprehensive narrative review of the literature. RESULTS: Research findings pinpoint altered pain perception and modulation processes as central neural mechanisms contributing to TMJD, highlighting the importance of personalized treatment approaches due to the disorder's complexity and patient variability. The study recognizes advances in neuroscience offering new treatment avenues, such as neuromodulation and biofeedback, which provide non-invasive and personalized options. However, it also addresses the challenges in TMJD research, such as the multifaceted nature of the disorder and the need for more comprehensive, interdisciplinary strategies in research and clinical practice. CONCLUSIONS: TMJD is a multifaceted disorder requiring an interdisciplinary approach for effective management. The study stresses the crucial role of neuroscience in understanding and treating TMJD, facilitating the development of innovative treatment strategies. It emphasizes the need for further research, advocating an integrated approach that combines neuroscience, dentistry, and psychology to address TMJD's complexities comprehensively and improve patient care, thereby enhancing the quality of life for affected individuals.

A Library of Polymer-based Microelectrode Array Designs for Recording from the Brain of Different Animal Models.

Large-scale network recording technology is critical in linking neural activity to behavior. Stable, long-term recordings collected from behaving animals are the foundation for understanding neural dynamics and the plasticity of neural circuits. Penetrating microelectrode arrays (MEAs) can obtain high-resolution neural activity from different brain regions. However, ensuring the longevity of implantable devices and the consistency of neural signals over time remains one big challenge. A potential solution is to use flexible, polymer-based MEAs to minimize the foreign body response and prolong the lifetime of neural interfacing devices. Rodents and nonhuman primates (NHP) are commonly used animal models in neuroscience and neuroengineering studies. Specially designed MEAs that capture morphological features of different animal brains and various brain structures are powerful tools to simultaneously obtain neural activities from multiple brain regions. In this work, we develop a set of prototype designs of polymer MEAs that cover cortical, sub-cortical, and multiple brain regions of rodents and NHP.

Adaptive polymer fiber neural device for drug delivery and enlarged illumination angle for neuromodulation.

Objective. Optical fiber devices constitute significant tools for the modulation and interrogation of neuronal circuitry in the mid and deep brain regions. The illuminated brain area during neuromodulation has a direct impact on the spatio-temporal properties of the brain activity and depends solely on the material and geometrical characteristics of the optical fibers. In the present work, we developed two different flexible polymer optical fibers (POFs) with integrated microfluidic channels (MFCs) and an ultra-high numerical aperture (UHNA) for enlarging the illumination angle to achieve efficient neuromodulation.Approach. Three distinct thermoplastic polymers: polysulfone, polycarbonate, and fluorinated ethylene propylene were used to fabricate two step-index UHNA POF neural devices using a scalable thermal drawing process. The POFs were characterized in terms of their illumination map as well as their fluid delivery capability in phantom and adult rat brain slices. Main results.A 100-fold reduced bending stiffness of the proposed fiber devices compared to their commercially available counterparts has been found. The integrated MFCs can controllably deliver dye (trypan blue) on-demand over a wide range of injection rates spanning from 10 nl min-1to 1000 nl min-1. Compared with commercial silica fibers, the proposed UHNA POFs exhibited an increased illumination area by 17% and 21% under 470 and 650 nm wavelength, respectively. In addition, a fluorescent light recording experiment has been conducted to demonstrate the ability of our UHNA POFs to be used as optical waveguides in fiber photometry.Significance. Our results overcome the current technological limitations of fiber implants that have limited illumination area and we suggest that soft neural fiber devices can be developed using different custom designs for illumination, collection, and photometry applications. We anticipate our work to pave the way towards the development of next-generation functional optical fibers for neuroscience.

Programmable DNA Nanodevices for Applications in Neuroscience.

The broad area of neuroscience has witnessed an increasing exploitation of a variety of synthetic biomaterials with controlled nanosized features. Different bionanomaterials offer very peculiar physicochemical and biochemcial properties contributing to the development of novel imaging devices toward imaging the brain, or as smartly functionalized scaffolds, or diverse tools contributing toward a better understanding of nervous tissue and its functions. DNA nanotechnology-based devices and scaffolds have emerged as ideal materials for cellular and tissue engineering due to their very biocompatible properties, robust adaptation with diverse biological systems, and biosafety in terms of reduced immune response triggering. Here we present technologies with respect to DNA nanodevices that are designed to better interact with nervous systems like neural cells, advanced molecular imaging technologies for imaging brain, biomaterials in neural regeneration, neuroprotection, and targeted delivery of drugs and small molecules across the blood-brain barrier. Along with comments regarding the progress of DNA nanotechnology in neuroscience, we also present a perspective on challenges and opportunities for applying DNA nanotechnology in applications pertaining to neurosciences.

Cryogel biomaterials for neuroscience applications.

Biomaterials in the form of 3D polymeric scaffolds have been used to create structurally and functionally biomimetic constructs of nervous system tissue. Such constructs can be used to model defects and disease or can be used to supplement neuronal tissue regeneration and repair. One such group of biomaterial scaffolds are hydrogels, which have been widely investigated for cell/tissue culture and as cell or molecule delivery systems in the field of neurosciences. However, a subset of hydrogels called cryogels, have shown to possess several distinct structural advantages over conventional hydrogel networks. Their macroporous structure, created via the time and resource efficient fabrication process (cryogelation) not only allows mass fluid transport throughout the structure, but also creates a high surface area to volume ratio for cell growth or drug loading. In addition, the macroporous structure of cryogels is ideal for applications in the central nervous system as they are very soft and spongey, yet also robust, which makes them a user-friendly and reproducible tool to address neuroscience challenges. In this review, we aim to provide the neuroscience community, who may not be familiar with the fundamental concepts of cryogels, an accessible summary of the basic information that pertain to their use in the brain and nervous tissue. We hope that this review shall initiate creative ways that cryogels could be further adapted and employed to tackle unsolved neuroscience challenges.

How Can Neuroscientists Respond to the Climate Emergency?

The world faces a climate emergency. Here, we consider the actions that can be taken by neuroscientists to tackle climate change. We encourage neuroscientists to put emissions reductions at the center of their everyday professional activities.

The neuroscience of sadness: A multidisciplinary synthesis and collaborative review.

Sadness is typically characterized by raised inner eyebrows, lowered corners of the mouth, reduced walking speed, and slumped posture. Ancient subcortical circuitry provides a neuroanatomical foundation, extending from dorsal periaqueductal grey to subgenual anterior cingulate, the latter of which is now a treatment target in disorders of sadness. Electrophysiological studies further emphasize a role for reduced left relative to right frontal asymmetry in sadness, underpinning interest in the transcranial stimulation of left dorsolateral prefrontal cortex as an antidepressant target. Neuroimaging studies - including meta-analyses - indicate that sadness is associated with reduced cortical activation, which may contribute to reduced parasympathetic inhibitory control over medullary cardioacceleratory circuits. Reduced cardiac control may - in part - contribute to epidemiological reports of reduced life expectancy in affective disorders, effects equivalent to heavy smoking. We suggest that the field may be moving toward a theoretical consensus, in which different models relating to basic emotion theory and psychological constructionism may be considered as complementary, working at different levels of the phylogenetic hierarchy.

The Evolution of Neuroscience as a Research Field Relevant to Dentistry.

The field of neuroscience did not exist as such when the Journal of Dental Research was founded 100 y ago. It has emerged as an important scientific field relevant to dentistry in view of the many neurally based functions manifested in the orofacial area (e.g., pain, taste, chewing, swallowing, salivation). This article reviews many of the novel insights that have been gained through neuroscience research into the neural basis of these functions and their clinical relevance to the diagnosis and management of pain and sensorimotor disorders. These include the neural pathways and brain circuitry underlying each of these functions and the role of nonneural as well as neural processes and their "plasticity" in modulating these functions and allowing for adaptation to tissue injury and pain and for learning or rehabilitation of orofacial functions.

Polydopamine-doped conductive polymer microelectrodes for neural recording and stimulation.

BACKGROUND: Microelectrodes have been widely used to detect and modulate the activities of neuronal networks. Various materials have been applied to microelectrode fabrication, and the conductive polymer is one of the most intensively explored material. The properties of conductive polymer highly depend on the incorporated material, so selecting it is essential. The mussel-inspired biomolecule, polydopamine (pDA), is known to provide unique chemical and mechanical properties to biological interfaces. NEW METHOD: pDA was incorporated into poly(3,4-ethylenedioxythiophene) (PEDOT) resulting in polydopamine PEDOT hybrid (PEDOT/pDA) microelectrode by an electrochemical deposition method. The electrical properties, such as impedance, charge storage capacity (CSC), and charge injection limit (CIL), of PEDOT/pDA microelectrodes, were characterized. RESULTS: PEDOT/pDA microelectrodes had low impedance, high CSC, and high CIL, which are prerequisite for neuronal signal recording and stimulation. Then, neuronal recordings and electrical stimulations were conducted to verify the functionality of the PEDOT/pDA microelectrodes. Spontaneous and evoked extracellular neuronal signals were successfully measured from cultured rat hippocampal neuronal networks, and the recorded signals showed excellent signal-to-noise ratio for the detection of extracellular spikes. COMPARISON WITH EXISTING METHODS: Compared with existing conductive polymer based neural electrodes, the PEDOT/pDA microelectrode had chemically functional material, pDA, embedded in the electrode, while it had comparable level of impedance and CSC and CIL for neural stimulation and recordings. CONCLUSIONS: We have shown that it is possible to fabricate a microelectrode array of pDA doped PEDOT microelectrodes and validated its performance for neuronal signal recording and electrical stimulation. The PEDOT/pDA microelectrode with excellent electrical performance and biocompatibility will be a promising tool for studying neuronal networks.

Bioresorbable photonic devices for the spectroscopic characterization of physiological status and neural activity.

Capabilities in real-time monitoring of internal physiological processes could inform pharmacological drug-delivery schedules, surgical intervention procedures and the management of recovery and rehabilitation. Current methods rely on external imaging techniques or implantable sensors, without the ability to provide continuous information over clinically relevant timescales, and/or with requirements in surgical procedures with associated costs and risks. Here, we describe injectable classes of photonic devices, made entirely of materials that naturally resorb and undergo clearance from the body after a controlled operational lifetime, for the spectroscopic characterization of targeted tissues and biofluids. As an example application, we show that the devices can be used for the continuous monitoring of cerebral temperature, oxygenation and neural activity in freely moving mice. These types of devices should prove useful in fundamental studies of disease pathology, in neuroscience research, in surgical procedures and in monitoring of recovery from injury or illness.

Integrating multi-unit electrophysiology and plastic culture dishes for network neuroscience.

The electrophysiological characterisation of cultured neurons is of paramount importance for drug discovery, safety pharmacology and basic research in the neurosciences. Technologies offering low cost, low technical complexity and potential for scalability towards high-throughput electrophysiology on in vitro neurons would be advantageous, in particular for screening purposes. Here we describe a plastic culture substrate supporting low-complexity multi-unit loose-patch recording and stimulation of developing networks while retaining manufacturability compatible with low-cost and large-scale production. Our hybrid polydimethylsilane (PDMS)-on-polystyrene structures include chambers (6 mm in diameter) and microchannels (25 microm x 3.7 microm x 1 mm) serving as substrate-embedded recording pipettes. Somas are plated and retained in the chambers due to geometrical constraints and their processes grow along the microchannels, effectively establishing a loose-patch configuration without human intervention. We demonstrate that off-the-shelf voltage-clamp, current-clamp and extracellular amplifiers can be used to record and stimulate multi-unit activity with the aid of our dishes. Spikes up to 50 pA in voltage-clamp and 300 microV in current-clamp modes are recorded in sparse and bursting activity patterns characteristic of 1 week-old hippocampal cultures. Moreover, spike sorting employing principal component analysis (PCA) confirms that single microchannels support the recording of multiple neurons. Overall, this work suggests a strategy to endow conventional culture plasticware with added functionality to enable cost-efficient network electrophysiology.