Reviews & Analysis

In this issue of Nature Neuroscience, Eshel et al. characterize the homogeneity with which individual dopamine neurons encode reward prediction error, a teaching signal that is thought to be crucial for associative learning.

Depression of AMPA receptor–mediated synaptic currents and impairment of long-term potentiation, triggered by amyloid-β, are the hallmarks of Alzheimer's pathophysiology. These dysfunctions are now linked to upregulated PDZ domain–dependent PTEN translocation to spines, contributing to cognitive deficits in model mice.

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.

The complexity of problems and data in psychiatry requires powerful computational approaches. Computational psychiatry is an emerging field encompassing mechanistic theory-driven models and theoretically agnostic data-driven analyses that use machine-learning techniques. Clinical applications will benefit from relating theoretically meaningful process variables to complex psychiatric outcomes through data-driven techniques.

The state of the nervous system shifts constantly. Most studies focus on how state determines the average neural response, with little attention to the trial-to-trial fluctuations of brain activity. We review recent theoretical advances in modeling the physiological mechanisms responsible for state-dependent modulations in the correlated fluctuations of neuronal populations.

Recent computational neuroscience developments have used deep neural networks to model neural responses in higher visual areas. This Perspective describes key algorithmic underpinnings in computer vision and artificial intelligence that have contributed to this progress and outlines how deep networks could drive future improvements in understanding sensory cortical processing.

What are the challenges associated with storing information over time in the brain? Here the authors explore the computational principles by which biological memory might be built. They develop a high-level view of shared problems and themes in short- and long-term memory and highlight questions for future research.

The networks used by computer scientists and by modelers in neuroscience frequently consider unit activities as continuous. Neurons, however, com­municate primarily through discontinuous spiking. This Perspective offers a unifying view of the current methods for transferring our ability to construct functional networks from continuous to more realistic spiking network models.

Despite representing a minority of cortical cells, inhibitory neurons deeply shape cortical responses. Inhibitory currents closely track excitatory currents, opening only brief windows of opportunity for a neuron to fire. This explains the variability of cortical spike trains, but may also, paradoxically, render a spiking network maximally efficient and precise.

Discrimination of neutral from harmful environments is important for survival. But how do salient contextual signals yield persisting memories? A study uncovers a circuit that increases the specificity of hippocampus-based memories.

Analysis of human hippocampus identifies two modules of coexpressed genes that are conserved throughout the human cortex and in mouse hippocampi. These modules are enriched for genetic variants associated with both cognitive phenotypes and neuropsychiatric disorders.

The most complete single-neuron transcriptome database of the mouse visual cortex was performed using a large collection of reporter mouse lines. Results highlight the unmatched neuronal diversity of the cerebral cortex.

A previously unknown mechanism contributes to dysfunction of the neurogenic niche during CNS autoimmunity. Natural killer cells are retained specifically in the subventricular zone in chronic disease, killing stem cells and promoting pathology.

Connections between a specific thalamic structure and the neocortex convey mismatches between internal perceptions and external events. These findings help to define the circuits controlling contextual modulation of visual-motor processing.

The role of transient elevations of the intracellular concentration of calcium in astrocytes is controversial. Some neuroscientists believe that, by triggering the release of 'gliotransmitters', astrocyte calcium transients regulate synaptic strength and neuronal excitability, while others deny that gliotransmission exists. Bazargani and Attwell assess the status of this rapidly evolving field.

Dynamic membrane transformations are not exclusively controlled by cytoskeletal rearrangement, but also by biophysical constraints, adhesive forces, membrane curvature and compaction. Recent technological advances have helped clarify longstanding controversies concerning myelination, from target selection to axon wrapping and membrane compaction. Chang et al. review these findings and discuss how understanding these processes provides insight into myelination-centered mechanisms of neural plasticity.

Central melanocortinergic signaling via the melanocortin-4 receptor is both a culprit in and a target for obesity. The authors review our understanding of this evolutionarily conserved system in the regulation of mammalian energy homeostasis.

Stuber and Wise review the role of the lateral hypothalamic area (LHA) in generating motivated behaviors related to feeding and reward processing. Classic experiments demonstrate that the LHA is critical for reward processing, and more contemporary approaches are beginning to elucidate the cells types and circuits required for these behaviors.