Perspectives

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.

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.

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.

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.

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.

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.

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.

Regions of the default mode network (DMN) are distributed across the brain and show patterns of activity that have linked them to various different functional domains. In this Perspective, Smallwood and colleagues consider how an examination of the topographic characteristics of the DMN can shed light on its contribution to cognition.

Neural network models have potential for improving our understanding of brain functions. In this Perspective, Pulvermüller and colleagues examine various aspects of such models that may need to be constrained to make them more neurobiologically realistic and therefore better tools for understanding brain function.

Evidence suggests that socio-economic status can affect not only the outcome of structural and functional development of the brain but also its rate. Tooley, Bassett and Mackey review this evidence and suggest that the valence and frequency of early experiences interact to influence brain development.

Neuroscience can explain cognition by considering single neurons and their connections (a ‘Sherringtonian’ view) or by considering neural spaces constructed by populations of neurons (a ‘Hopfieldian’ view). In this Perspective, Barack and Krakauer argue that the Hopfieldian view has the conceptual resources to explain cognition more fully the Sherringtonian view.

In this Perspective, Koban, Gianaros, Kober and Wager describe neural systems that construct models of the ‘self-in-context’. Such models endow events with personal meaning and enable predictive control over behaviour and peripheral physiology — with implications for health and disease.

The role of the default mode network (DMN) is unclear. In this Perspective, Yeshurun, Nguyen and Hasson review evidence that the DMN integrates extrinsic inputs with intrinsic information over long timescales, enabling it to represent meaning in a way that can be shared between individuals.

Deep neural networks may offer theories of perception, cognition and action for biological brains. Here, Saxe, Nelli and Summerfield offer a road map of how neuroscientists can use deep networks to model and understand biological brains.

Mounting evidence suggests that the gut microbiome impacts brain function, and mechanistic connections between specific microbial by-products and the brain have begun to emerge. In this Perspective, Mazmanian and colleagues discuss the assortment of microbial molecules currently thought to mediate these gut–brain connections.

Major compelling questions about the functional role of the locus coeruleus nucleus that had been difficult to answer, given its remote location and diminutive size, have now become accessible via new neuroscience tools. In this Perspective, 14 investigators provide a historical context for recent discoveries and outline new vistas for investigation.

Reinforcement learning has been suggested to come in two flavours: model-free and model-based. In this Perspective, Collins and Cockburn explain why viewing reinforcement learning through this dichotomous lens is not always accurate or helpful, and suggest paths forward.

Although inputs and outputs that carry social signals are anatomically restricted to distinct subnuclear regions of the amygdala, social behaviours are not. This fact may be explained by the operation of multidimensional processing in parallel with subcircuits of genetically identical neurons that serve specialized and functionally dissociable functions.

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.