Review Articles in 2021

Stress, a key risk factor for many neuropsychiatric disorders, drives a range of maladaptive physiological changes from genetic to behavioural levels. In this review, Sanacora et al. discuss the mechanisms underlying susceptibility and resilience to acute and chronic stress.

The translation of analgesic drug candidates to the clinic relies upon successful preclinical pain modelling. In this Review, Stucky and colleagues describe recent trends in the methods used to model pain in laboratory animals and provide recommendations for experimental designs that may increase translational success.

Numerous energy-demanding cellular processes contribute to synaptic activity and function. Li and Sheng describe the mechanisms that regulate presynaptic energy supply to ensure that neurons can meet these demands and maintain their functions during periods of intensive synaptic activity.

Synaptic dysfunction is a key feature of Alzheimer disease. In this Review, Padmanabhan, Kneynsberg and Götz examine insights provided by super-resolution microscopy into synaptic architecture and organization in Alzheimer disease, focusing on amyloid-β and tau, thought to be two key players in the pathophysiology of the disease.

Hands enable us to interact with objects in precise and versatile ways. In this Review, Sobinov and Bensmaia discuss aspects of mundane and expert manual behaviours, the anatomical complexity of the human hand and neural mechanisms that underlie manual dexterity.

Fibroblasts in the CNS have been assigned a role in fibrotic scar formation in response to injury and inflammation but might perform additional roles attributed to other cell types. In this Review, Dorrier and colleagues discuss the available evidence regarding fibroblast functions in the CNS.

The sympathetic regulation of bodily functions relies on precise connections between sympathetic neurons and peripheral organs. In this Review, Scott-Solomon and colleagues discuss the mechanisms underlying the development of the sympathetic nervous system and provide insight into disorders regulated by this branch of the nervous system.

Male-only studies predominate preclinical research on anxiety and depression. In this Review, Bangasser and Cuarenta discuss how, since the inclusion of female subjects, new mechanisms have been identified that underlie vulnerability to these disorders, and that reveal novel targets for treatments.

Neural circuits in the mammalian central nervous system are modified in response to neural activity during development. In this Review, Faust and colleagues provide an overview of the mechanisms underlying developmental synaptic pruning and how alterations in this process can occur in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia.

The 'new head' hypothesis proposes that the advent of the neural crest and cranial placodes was crucial for the evolution of vertebrates. In this Review, Martik and Bronner discuss this hypothesis and how emerging data about gene regulatory networks in neural crest-like cell types in invertebrate chordates are providing insights into neural crest evolution.

Human pluripotent stem cell-derived in vitro models have potential as tools to study aspects of human brain development. Here, Heilshorn and colleagues review biomaterial-based approaches that may be integrated into these models in an effort to develop them further and better recapitulate neurodevelopmental processes.

Many studies implicate a prefrontal–basal ganglia circuit in the control of action-stopping. Here, Ricci Hannah and Adam Aron provide an update of studies of this circuit, discuss its clinical relevance, and consider whether its action-stopping function applies in real-world scenarios, beyond the laboratory.

Mammalian skin contains an array of specialized structures that transform mechanical forces into electrical signals. Handler and Ginty provide a comprehensive overview of the features of the skin’s mechanosensory end organs and the neurons with which they associate and consider how their diverse properties contribute to the sense of touch.

The brain is particularly susceptible to injury after ischaemia; however, emerging evidence suggests that, under certain conditions, it may show more resilience. Daniele et al. review the effects of ischaemia on the brain and efforts to study and protect the post-ischaemic brain.

The capacity to navigate to a previously encountered or predicted reward, such as food or safety, is crucial for survival. Here, Sosa and Giocomo examine the neural mechanisms that encode reward location and propose key roles for the hippocampus and the entorhinal cortex in storing and retrieving reward-related information in the brain.

Neocortical circuits imparting specificity and causality to pain are not well understood. In this Review, Kuner and Tan discuss new insights into the contributions of diverse cerebral domains, their connectivity and their plasticity to the sensory and emotional aspects of pain.

Dendritic spines can be considered to embody algorithms that underlie various brain functions. Here, Kasai et al. review spine dynamics and their roles in various brain functions, compare these dynamics with parallels in machine learning and describe how disrupted dynamics may contribute to mental disorders.

Acute cannabis exposure modulates numerous aspects of neurocognitive function; however, the effects experienced by individuals are highly variable. Ramaekers and colleagues here review the neural basis of cannabis-induced neurocognitive changes and response variability, and consider the legal, therapeutic and societal implications.

Sociopolitical changes regarding cannabis and its potential harm for vulnerable populations raise concern as more pregnant women and teens use cannabis. Hurd and colleagues discuss neurobiological effects of cannabis exposure during development and highlight an epigenetic link for synaptic reprogramming.

The neocortex and the thalamus are connected by looping circuits, enabling cortical function. In this Review, Gordon Shepherd and Naoki Yamawaki examine the patterns of connectivity between the major types of cortical and thalamic neurons and how these cortico-thalamo-cortical loops relate to corticocortical circuits.