Reviews & Analysis

The recollection of memories and voluntary actions are often perceived to be generated spontaneously. In this Perspective, Itzhak Fried examines evidence from human single-neuron studies indicating that brain systems involved in these acts can form a conceptual–volition interface, where representations of actions and stored memories interact, sometimes in the absence of sensory input and sometimes allowing such input to be overridden.

A prevailing theory of Parkinson disease pathogenesis revolves around the spread of α-synuclein toxicity from the periphery to the brain. In this Review, Blesa and colleagues discuss the idea that, although these bottom-up mechanisms are involved, early neuronal loss in the nigrostriatal system also plays a prominent role.

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.

The amyloid hypothesis has been the dominant model for the pathogenesis of Alzheimer disease for several decades. In this Perspective, Giovanni Frisoni and colleagues examine evidence for and against this hypothesis before outlining an alternative model, the probabilistic model of Alzheimer disease.

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.

Environmental stressors, including extreme ambient temperature, the presence of pathogens or predators, and a lack of food, can profoundly influence animal behaviour. In this Perspective, Nakamura, Nakamura and Kataoka present a hypothalamomedullary network model for physiological responses to various environmental stressors.

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 encoding of itch by peripheral and central neural circuits is a topic of long-standing interest in the somatosensory field. Here, Zhou-Feng Chen outlines a model for itch coding that emphasizes the role of neuropeptides in conveying itch information from the periphery to the spinal cord.

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.

Developing a better understanding of neural codes should enable the links between stimuli, brain activity and behaviour to become clearer. In this Perspective, Kriegeskorte and Wei examine neural tuning and representational geometry — complementary approaches used to understand neural codes — and the relationship between them.

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.

Entorhinal cortical grid cells have been suggested to encode an internal map of the environment during spatial navigation. In this Perspective, Rueckemann, Sosa and colleagues propose that grid cells and hippocampal place cells cooperate to provide a topological representation of experience through temporal ordering of events, in both spatial and non-spatial contexts.

Homeobox genes were initially characterized on the basis of the homeotic transformations in segmental identity during development that resulted from mutation of the Hox cluster family of homeobox genes. In this Perspective article, Hobert proposes that homeobox genes specify neuronal identity in the nematode Caenorhabditis elegans and possibly in other animals too.

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.

How category-specific regions of cortex, or ‘domains’, in the primate ventral stream arise is unclear. In this Perspective, Arcaro and Livingstone present a ‘bottom-up’ model for the generation of these domains, whereby experience refines a domain-general architecture based on topographic maps of the sensory environment.