Perspectives

The authors review the most recent measurement and manipulation approaches that enable links between synaptic plasticity and learning to be examined, and they propose potential future approaches to tackle this endeavor.

In this Perspective, Josh Berke discusses recent developments in the study of dopamine function. He proposes a model that explains how dopamine can serve as both a learning signal and as a critical modulator of motivated decision-making.

Microglial immune checkpoint mechanisms are signaling pathways that limit immune responsiveness and promote homeostatic activities of micrroglia throughout life, but can interfere with repair mechanisms in disease.

The authors argue that intracranial EEG recordings in humans add unique information beyond invasive recordings in animal models and noninvasive human research, including anatomically precise dynamics and network interactions of neuronal populations.

The authors discuss newly emerging evidence for the role of the transcription factor CREB in memory, including its role in modulating changes in excitability that are critical for neural assembly formation and linking of memories across time.

Research in adolescent neurocognitive development has focussed largely on averages, but there is substantial individual variation in development. This Perspective proposes that the field should move towards studying individual differences.

The key driver of early-stage Alzheimer’s pathophysiology remains controversial. Styr and Slutsky propose that failures in firing homeostasis and imbalance between stability and plasticity represent the driving force of early disease progression.

The glial scar plays critical but divergent roles during regeneration of the mammalian CNS. Here the authors propose that in-depth analysis of the functionally heterogeneous populations of reactive glia within the scar is needed to fully understand the glial scar’s dual nature.

In this Perspective, the authors propose that functional insights into generalist cortical computation may reside at the level of population patterns rather than functionally defined cell types. They then review results showing that medial entorhinal cortex (MEC) neurons exhibit substantial heterogeneity, suggesting MEC is a generalist circuit that computes diverse episodic states.

Considerable progress has been made in understanding how the brain encodes our sense of direction. This Perspective considers the link between self-motion detection and navigation circuits and discusses future challenges for establishing the neural mechanisms responsible for sensing direction in both real-world and virtual-reality environments.

Reinforcement learning (RL) is the behavioral process of learning to associate rewards with actions or objects. Conceptual and theoretical accounts of RL have focused on the striatum. However, recent data shows that the amygdala also plays an important role in RL.

A revolution is underway in cognitive neuroscience, where tools and techniques from computer science and the tech industry are helping to extract more meaningful cognitive signals from noisy and increasingly large fMRI datasets. In this paper, the authors review the cutting edge of such computational analyses and discuss future opportunities and challenges.

The study of the mechanisms controlling RNA metabolism in neurons represents a new frontier in the understanding of gene–environment interactions and how they regulate brain function. In this Perspective, the authors describe the recent surge in newly identified epitranscriptomic processes and highlight their potential importance in coordinating the molecular underpinnings of cognition and memory.

A number of higher cognitive processes are linked to dorsal anterior cingulate cortex (dACC), yet its overall functions remain elusive. The authors discuss convergent findings suggesting it is part of a mechanism for tracking and evaluating reward environments in order to implement learning, search and goal-driven persistence.

The authors propose that dorsal anterior cingulate cortex (dACC) performs a cost/benefit analysis to specify how best to allocate cognitive control. They describe why this theory accounts well for dACC’s role in decision-making, motivation and cognitive control, including its observed role in foraging choice settings.

Given recent advances in genome engineering technology like CRISPR and the difficulty of modeling human diseases in rodents, transgenic nonhuman primates may be used to develop etiologically relevant models of disease. This perspective by Guoping Feng et al. highlights the technological advances, potential challenges and opportunities these models present to furthering our understanding of disease.

In the twenty-first century, microglia came of age. Their remarkable ontogeny, unique functions and gene expression profile, process motility, and disease relevance have all been highlighted. Neuroscientists interested in microglia encounter an obsolete concept, M1/M2 polarization, suggesting experimental strategies that produce neither conceptual nor technical advances. Ransohoff's Perspective argues against applying this flawed paradigm.

In this Perspective the authors provide a comparison of recent neurophysiological findings on the pathophysiology of three major movement disorders: Huntington's disease, l-DOPA-induced dyskinesia and dystonia. Both clinical and preclinical studies show that these hyperkinetic disorders share mechanisms underlying synaptic scaling and synaptic plasticity alterations in the basal ganglia–thalamo-cortical network.

In this Perspective, Murray Sherman discusses connectivity in the thalamocortical system, including the evidence that cortical areas are connected in parallel by direct and transthalamic pathways. Because thalamus receives inputs that form collaterals with subcortical motor regions, the author suggests that it may relay efference copy information.

The authors use recent probabilistic theories of neural computation to argue that confidence and certainty are not identical concepts. They propose precise mathematical definitions for both of these concepts and discuss putative neural representations.