20th Anniversary

Nature Reviews Neuroscience was first published in October 2000. In this issue, we therefore mark the 20th anniversary of the journal.

To mark the 20th anniversary of Nature Reviews Neuroscience, in this Viewpoint article we asked some of the researchers who have authored pieces published in the journal in recent years for their views on how the field, and their areas within it, have developed over the past two decades.

Although not electrically excitable, astrocytes display a complex repertoire of intracellular Ca²⁺ signalling. Semyanov, Henneberger and Agarwal describe experimental preparations and methods for studying Ca²⁺ activity in astrocytes, their limitations and the ongoing technical and conceptual challenges in the interpretation of astrocytic Ca²⁺ events and their spatio-temporal patterns.

The causal role of chromatin modifications has been difficult to study in the brains of behaving animals. Yim, Teague and Nestler review locus-specific neuroepigenome-editing tools to define causal relationships between chromatin modifications and their molecular, cellular, circuit and behavioural consequences.

Models of dendrites have been instrumental in our understanding of their functions. Poirazi and Papoutsi review the major contributions of dendritic models, including those already proved or waiting to be experimentally verified, and highlight successful interactions between the modelling and experimental neuroscience communities.

Much progress has been made in understanding astrocytes, but details on their functions and interactions remain difficult to determine. Yu, Nagai and Khakh give an overview of recent advances in the toolbox for molecular, genetic, morphological and physiological investigations into astrocytes.

Tissue-clearing methods are now allowing 3D imaging of intact tissues and some entire mammals. In this Review, Ueda and colleagues discuss the various tissue-clearing methods, related techniques and data analysis and management, as well as the application of these methods in neuroscience.

Genetically encoded voltage indicators (GEVIs) are emerging tools to elucidate the inner workings of the brain. In this Review, Knopfel and Song outline the potentials of GEVI imaging based on recent neurotechnological and conceptual advances in the brain sciences.

Optopharmacology enables endogenous ligands, receptors and ion channels to be rendered sensitive to light. Paoletti, Ellis-Davies and Mourot give an overview of current optopharmacological techniques and tools and describe the neuroscientific insights they have uncovered.

Studies that examine brain activity during real-time social interactions may advance our understanding of human social behaviour. Redcay and Schilbach describe progress in ‘second-person’ neuroscience and discuss the insights into the brain mechanisms of social behaviour that have been gained.

Here, Hong and Lieber review recent developments in electrode technologies for the recording of single-unit spiking activity. They focus on advances in electrodes with high spatial integration, long-term stability and multifunctional capacities.

The brain can be parcellated into areas or networks with different structural or functional properties. Eickhoff, Yeo and Genon describe various imaging-based strategies to parcellate the human brain, including those based on local properties, such as cytoarchitecture, and global properties, such as connectivity.

Rodent models are extensively used to investigate the pathophysiology of Alzheimer disease. In this Review, Götz, Bodea and Goedert critically examine the approaches that have been adopted to generate rodent Alzheimer disease models and touch on some of the lessons that have been learned from their use.

Modern network neuroscience involves the use of various types of models to understand the brain. In this Review, Bassett, Zurn and Gold discuss the aims of this approach before examining how network models may be categorized and validated.

In recent years, several studies have reported the production of microglia-like cells from induced pluripotent stem cells. Pocock and Piers describe the methods used to produce and analyse these cells and their potential to improve our understanding of microglial function.

By capturing and manipulating the self-organizing capacity of pluripotent stem cells, researchers have established protocols for the production ofin vitrobrain-like 'organoids'. Di Lullo and Kriegstein evaluate approaches to organoid generation and consider their potential as models of brain development and disease.

Attempts to group the cells of the nervous system into classes or types face technical and conceptual barriers. Zeng and Sanes consider the current approaches to classification and propose a strategy and set of principles to guide future classification efforts.

Optogenetics is widely used to study the consequences of neuronal activity with high spatiotemporal precision. In this Review, Kimet al. discuss the integration of this approach with other technological and methodological advances to gain insights into neuronal function that were previously inaccessible.

Cultures of human neural cells can be generated from skin cells that have been reprogrammed to produce induced pluripotent stem cells (iPSCs) or subjected to direct conversion. Gage and colleagues describe advances in differentiation protocols that allow specific subtypes of neural cell to be produced and consider the advantages and disadvantages of different approaches.

Recent years have seen several important advances in the tools available to interrogate the function of specific genes. Here, Heidenreich and Zhang describe the advantages of the precise and efficient CRISPR–Cas9 (clustered regularly interspaced short palindromic repeat–CRISPR-associated protein) system for gene editing and outline how this approach may benefit research into nervous system function and disease.

Scientific meetings are an opportunity to promote research and researchers. Anne-Marie M. Oswald and Srdjan Ostojic describe ways to promote diversity at the conference podium.

Although neuroscientists focus on only very few animal species today, there are many important reasons to take advantage of model system diversity and embrace (anew) a comparative approach in modern brain research. Recent technological advances make this increasingly possible.

In this Perspective, Hanno Würbel and colleagues argue that a disregard for incorporating biological variation in study design is an important cause of poor reproducibility in animal research. They put the case for the use of systematic heterogenization of study samples and conditions in studies to improve reproducibility.

Neuroscience laboratories can take steps to ‘go green’ in a number of ways, including curbing unnecessary energy usage and reducing plastic waste. Such measures often rely on behavioural changes but need not affect scientific output.

In recent years, several funding agencies have introduced requirements for researchers to consider sex as a biological variable in preclinical research. In this Comment article, McCarthy and colleagues discuss the potential impact of these policies for neuroscience research.

Neuroimaging techniques are increasingly applied by the wider neuroscience community. However, problems such as low statistical power, flexibility in data analysis and software issues pose challenges to interpreting neuroimaging data in a meaningful and reliable way. Here, Poldracket al. discuss these and other problems, and suggest solutions.

Churchland and Sejnowski consider how the BRAIN Initiative will bring together theoretical and experimental neuroscience to drive the development of conceptual frameworks of brain function.

James Olds argues that gaining a true understanding of brain structure and function will require neuroscientists to adopt a team-based approach to research and considers some of the challenges that this presents for the field.

Low-powered studies lead to overestimates of effect size and low reproducibility of results. In this Analysis article, Munafò and colleagues show that the average statistical power of studies in the neurosciences is very low, discuss ethical implications of low-powered studies and provide recommendations to improve research practices.

Neuroscientists face increasing pressure to disseminate results and discuss their implications with the public. Illes and colleagues consider the challenges that they face and make specific recommendations for individuals and institutions to promote this process.

Recent improvements in the technology available for the analysis of genetic variability have revolutionized the study of many diseases. Hardy and colleagues illustrate how genome-wide strategies, including whole-genome and whole-exome sequencing, have been used to improve our understanding of the pathobiological mechanisms of neurological diseases

The diagnosis of autism is based on behavioural criteria. Robust phenotypes in mouse models hold great promise for the discovery of effective treatments for the core symptoms of autism spectrum disorders. Crawley and colleagues review the behavioural assays that are most relevant to the symptoms of human autism, along with the essential control measures.

In recent years, the principles of network science have increasingly been applied to the study of the brain's structural and functional organization. Bullmore and Sporns review this growing field of research and discuss its contributions to our understanding of brain function.

Recording from neuronal populations is a promising and powerful neuroscience technique; however, interpreting the resulting spike trains presents several challenges. Quian Quiroga and Panzeri discuss how decoding algorithms and information theory can be used to extract information from population recordings.

Advances in cellular imaging have been crucial for improving our understanding of many aspects of neuroscience. Kerr and Denk describe how sophisticated optical imaging techniques allow us to image activity in single neurons or neuron populations in living animals.

Newly emerging techniques will revolutionize our understanding of the mammalian brain. Deisseroth and colleagues detail the development and use of microbial opsins as optogenetic tools for the study of neural circuits and discuss the use of these tools as potential future therapies for neurological disorders.

Data sharing in neuroscience remains relatively rare. Ascoli describes the obstacles that need to be overcome, and highlights the great potential for sharing neuronal morphology data as a starting point to mobilize data sharing in the wider neuroscience community.