Reviews & Analysis

The authors review studies of basal ganglia (BG) physiology in the context of the indirect/direct pathway model of the BG. Noting work that is inconsistent with an exclusive role of the direct pathway in promoting movement and indirect pathway inhibiting movement, they propose a revision of the model incorporating recent findings.

In this paper, Womelsdorf and colleagues review the recent advances in our understanding of how rhythmic activity across multiple frequency bands and brain areas affects neural computations. The authors suggest a dynamic tripartite motif framework that links the activity signatures of given circuits with their structural elements and the proposed computational output.

The orbitofrontal cortex and ventral striatum encode expected outcomes during economic decision-making. Research now demonstrates that activity in these structures also represents missed opportunities during a foraging task cleverly designed to elicit regret in rats, the Restaurant Row task.

A report reveals that giant subcortical heterotopia is caused by mutation of a microtubule-associated protein, Eml1. Defects in Eml1 lead to disruption of the radial migratory scaffolding network in mice and humans.

The proliferation of NSCs in the adult SVZ is controlled by a set of neurons expressing choline acetyltransferase, identifying a mechanism connecting brain activity to neurogenesis in the adult mammalian brain.

A leading therapeutic molecule for multiple sclerosis, FTY720, is shown to mimic a key component of sphingolipid signaling, resulting in specific manipulation of histone deacetylases and the extinction of memory.

This Review discusses the molecular mechanisms by which neuronal identity is maintained throughout animals' development and lives. Drawing from the invertebrate and vertebrate literature, Deneris and Hobert also describe common themes, where the initial specification of neurons and subsequent maintenance of cell identity may share transcriptional programming and transcription factors. The piece also discusses such mechanism's implications for neurological diseases.

A study now shows that variability in neuronal responses in the visual system mainly arises from slow fluctuations in excitability, presumably caused by factors of nonsensory origin, such as arousal, attention or anesthesia.

We now learn that mutant huntingtin binds to a complex that imports constituent proteins across the mitochondrial inner membrane, halting bioenergetics in synaptic mitochondria and predisposing to neuronal dysfunction and death.

Spike-based approaches to feature selectivity in sensory pathways can bias toward only the most active neurons. A subthreshold method identifies feature selectivity in the rodent vibrissal system regardless of spiking activity.

Brain-computer interfaces (BCIs) and optical imaging have both undergone impressive technological growth in recent years. A study in which mice learn to modulate neural activity merges these technologies to investigate the neural basis of BCI learning with unprecedented spatial detail.

Stimulating the brain in the gamma frequency range, which is the frequency band most often associated with conscious awareness in the awake state, boosts the ability to engage in lucid dreaming during REM sleep.

It is now possible to systematically identify, on a genome-wide scale, genetic variants for disease, how often they occur in the population and how large their impact is on risk. In this Review, the authors discuss recent findings regarding the genetic architecture of psychiatric disorders and the contribution of common but weak and rare but strong variants to disease risk.

Large-scale collaborative efforts coupled with new genomic technologies now allow reliable detection of genetic variants influencing risk for major psychiatric and neurodevelopmental disorders. In this Perspective the authors provide a primer on current genome-wide efforts to identify risk variants and how these may be translated into neurobiological insights.

Understanding how genetic variation contributes to normal and pathological brain function requires integrating genetic and neuroimaging studies. New imaging consortia now make it possible to systematically assess the impact of genetic variation on the structure and function of the brain on a whole-genome and whole-brain level. In this Review, the authors summarize efforts to combine genome-wide studies with brain imaging and discuss the statistical and methodological issues necessary to insure rigor and robustness in this rapidly developing field.

Advances in genome sequencing technologies have revolutionized the search for rare and penetrant mutations leading to diseases such as autism. Given that all individuals carry new and disruptive mutations, in this Review, the authors discuss ways to home in on pathogenic mutations associated with neurodevelopmental disorders.

Mutations in Mendelian disease genes often lead to distinct clinical presentations, and the same non-specific risk is now apparent for many neuropsychiatric disorders. In this Review, the authors analyze pathogenic mechanisms for known Mendelian disease and discuss what it means for understanding the causes of non-specific genetic risk in more complex brain diseases.

Grid cells have been proposed to reflect competitive interactions in inhibitory neural networks. Experimental results obtained using optogenetics to identify spikes emitted specifically by parvalbumin interneurons now constrain the mechanisms by which such networks could give rise to grid cells.

It is widely believed that Huntington's disease is driven exclusively by neuronal dysfunction. Work now challenges this view, showing that mutant huntingtin in astrocytes leads to dysregulation of extracellular K⁺.