Cancer neuroscience: State of the field, emerging directions.

The nervous system governs both ontogeny and oncology. Regulating organogenesis during development, maintaining homeostasis, and promoting plasticity throughout life, the nervous system plays parallel roles in the regulation of cancers. Foundational discoveries have elucidated direct paracrine and electrochemical communication between neurons and cancer cells, as well as indirect interactions through neural effects on the immune system and stromal cells in the tumor microenvironment in a wide range of malignancies. Nervous system-cancer interactions can regulate oncogenesis, growth, invasion and metastatic spread, treatment resistance, stimulation of tumor-promoting inflammation, and impairment of anti-cancer immunity. Progress in cancer neuroscience may create an important new pillar of cancer therapy.

The application of artificial intelligence to biology and neuroscience.

Over the last decade, the artificial intelligence (AI) has undergone a revolution that is poised to transform the economy, society, and science. The pace of progress is staggering, and problems that seemed intractable just a few years ago have now been solved. The intersection between neuroscience and AI is particularly exciting.

We like neurons.

Charleese Williams is the winner of the 2021 Rising Black Scientists Award for an undergraduate scholar. For this award, we asked emerging Black scientists to tell us about the experiences that sparked their interest in the life sciences, their vision and goals, and how they want to contribute to a more inclusive scientific community. This is her story.

BRAIN 2.0: Transforming neuroscience.

The NIH BRAIN Initiative is entering a new phase. Three large new projects-a comprehensive human brain cell atlas, a whole mammalian brain microconnectivity map, and tools for precision access to brain cell types-promise to transform neuroscience research and the treatment of human brain disorders.

Fluorescence imaging of large-scale neural ensemble dynamics.

Recent progress in fluorescence imaging allows neuroscientists to observe the dynamics of thousands of individual neurons, identified genetically or by their connectivity, across multiple brain areas and for extended durations in awake behaving mammals. We discuss advances in fluorescent indicators of neural activity, viral and genetic methods to express these indicators, chronic animal preparations for long-term imaging studies, and microscopes to monitor and manipulate the activity of large neural ensembles. Ca2+ imaging studies of neural activity can track brain area interactions and distributed information processing at cellular resolution. Across smaller spatial scales, high-speed voltage imaging reveals the distinctive spiking patterns and coding properties of targeted neuron types. Collectively, these innovations will propel studies of brain function and dovetail with ongoing neuroscience initiatives to identify new neuron types and develop widely applicable, non-human primate models. The optical toolkit's growing sophistication also suggests that "brain observatory" facilities would be useful open resources for future brain-imaging studies.

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.

Roadmap for the Emerging Field of Cancer Neuroscience.

Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of "cancer neuroscience" and encourage multidisciplinary collaboration for the study of cancer-nervous system interactions.

Working across Disciplines in Neuroscience.

Neuroscience has a deep history of close collaborations across fields. With modern technologies continuing to broaden the horizon of neuroscience research, we asked neuroscientists to share their views on the advantages and challenges of forging collaborations across disciplines.

In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images.

Microscopy is a central method in life sciences. Many popular methods, such as antibody labeling, are used to add physical fluorescent labels to specific cellular constituents. However, these approaches have significant drawbacks, including inconsistency; limitations in the number of simultaneous labels because of spectral overlap; and necessary perturbations of the experiment, such as fixing the cells, to generate the measurement. Here, we show that a computational machine-learning approach, which we call "in silico labeling" (ISL), reliably predicts some fluorescent labels from transmitted-light images of unlabeled fixed or live biological samples. ISL predicts a range of labels, such as those for nuclei, cell type (e.g., neural), and cell state (e.g., cell death). Because prediction happens in silico, the method is consistent, is not limited by spectral overlap, and does not disturb the experiment. ISL generates biological measurements that would otherwise be problematic or impossible to acquire.

Toward a Global BRAIN Initiative.

Neuroscience is entering a collaborative era in which powerful new technologies, generated by large scientific projects in many countries, will have a dramatic impact on science, medicine, and society. Coordinating these international initiatives and ensuring broad distribution of novel technologies and open accessibility of the generated data will multiply their value, while tapping creativity and expertise from every source.

Neural Circuits for Emotion.

Emotions are fundamental to our experience and behavior, affecting and motivating all aspects of our lives. Scientists of various disciplines have been fascinated by emotions for centuries, yet even today vigorous debates abound about how to define emotions and how to best study their neural underpinnings. Defining emotions from an evolutionary perspective and acknowledging their important functional roles in supporting survival allows the study of emotion states in diverse species. This approach enables taking advantage of modern tools in behavioral, systems, and circuit neurosciences, allowing the precise dissection of neural mechanisms and behavior underlying emotion processes in model organisms. Here we review findings about the neural circuit mechanisms underlying emotion processing across species and try to identify points of convergence as well as important next steps in the pursuit of understanding how emotions emerge from neural activity.

Catching the Brain in the Act.

Understanding how genes within cells, and cells within circuits, function together to produce the extraordinary repertoire of animal behaviors is arguably one of the most challenging undertakings in neuroscience. Two papers in this issue move toward this goal via 3D imaging of active neurons across the entire mouse brain.

Brain Exploration, Off the Beaten Path.

Model organisms, such as rodents, monkeys, or Drosophila, have driven much of recent research in neuroscience. However, studies in other, more unusual systems have broadened the types of questions that are being asked and have revealed the diverse ways in which species tackle common problems. Cell editor Mirna Kvajo talked with Nachum Ulanovsky, Gilles Laurent, and Anthony Leonardo about their research and how studying bats, reptiles, and dragonflies informs big questions in neuroscience. An annotated excerpt of the conversation appears below, and the full conversation is available with the article online. PAPERCLIP.

Cell-Type-Specific Optogenetics in Monkeys.

The recent advent of technologies enabling cell-type-specific recording and manipulation of neuronal activity spurred tremendous progress in neuroscience. However, they have been largely limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a generalizable method for achieving cell-type specificity in monkeys.

On the Necessity of Ethical Guidelines for Novel Neurotechnologies.

Because novel neurotechnologies may alter human identity and society in profound ways, we advocate for the early integration of ethics into neurotechnology. We recommend developing and adopting a set of guidelines, like the Belmont Report on human subject research, as a framework for development and use of brain-related technologies.

Melding Synthetic Molecules and Genetically Encoded Proteins to Forge New Tools for Neuroscience.

Unraveling the complexity of the brain requires sophisticated methods to probe and perturb neurobiological processes with high spatiotemporal control. The field of chemical biology has produced general strategies to combine the molecular specificity of small-molecule tools with the cellular specificity of genetically encoded reagents. Here, we survey the application, refinement, and extension of these hybrid small-molecule:protein methods to problems in neuroscience, which yields powerful reagents to precisely measure and manipulate neural systems.

Large-scale neurophysiology and single-cell profiling in human neuroscience.

Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.

A Common Space Approach to Comparative Neuroscience.

Comparative neuroscience is entering the era of big data. New high-throughput methods and data-sharing initiatives have resulted in the availability of large, digital data sets containing many types of data from ever more species. Here, we present a framework for exploiting the new possibilities offered. The multimodality of the data allows vertical translations, which are comparisons of different aspects of brain organization within a single species and across scales. Horizontal translations compare particular aspects of brain organization across species, often by building abstract feature spaces. Combining vertical and horizontal translations allows for more sophisticated comparisons, including relating principles of brain organization across species by contrasting horizontal translations, and for making formal predictions of unobtainable data based on observed results in a model species.

Current Status of and Perspectives on the Application of Marmosets in Neurobiology.

The common marmoset (Callithrix jacchus), a small New World primate, is receiving substantial attention in the neuroscience and biomedical science fields because its anatomical features, functional and behavioral characteristics, and reproductive features and its amenability to available genetic modification technologies make it an attractive experimental subject. In this review, I outline the progress of marmoset neuroscience research and summarize both the current status (opportunities and limitations) of and the future perspectives on the application of marmosets in neuroscience and disease modeling.

Spatial Transcriptomics: Molecular Maps of the Mammalian Brain.

Maps of the nervous system inspire experiments and theories in neuroscience. Advances in molecular biology over the past decades have revolutionized the definition of cell and tissue identity. Spatial transcriptomics has opened up a new era in neuroanatomy, where the unsupervised and unbiased exploration of the molecular signatures of tissue organization will give rise to a new generation of brain maps. We propose that the molecular classification of brain regions on the basis of their gene expression profile can circumvent subjective neuroanatomical definitions and produce common reference frameworks that can incorporate cell types, connectivity, activity, and other modalities. Here we review the technological and conceptual advances made possible by spatial transcriptomics in the context of advancing neuroanatomy and discuss how molecular neuroanatomy can redefine mapping of the nervous system.