Reviews & Analysis

The use of patient-derived stem cells for in vitro neurodegenerative disease modeling has gained much traction in recent years. In this review, the authors examine the potential caveats and pitfalls of stem cell use and highlight insights from the literature that suggest methods for overcoming these difficulties.

The strength and versatility of optogenetics rely not only on the diversity of the optogene toolkit but also on the ability to achieve spatially selective and temporally precise control of electrical activity in specific neural circuits, individual cells or subcellular compartments. This remains a challenge and requires sophisticated experimental designs. In this article, Packer, Roska and Häusser discuss the myriad combinations of optical, anatomical and genetic strategies that can be used to manipulate neuronal activity with light.

In this review article, the authors give a brief overview of the sensory capabilities of rodents and of their cortical areas devoted to sensation and decision. They also review methods of psychophysics, focusing on the technical issues that arise in their implementation in rodents.

Immunogold techniques allow target proteins to be localized subcellularly quantitatively and with high precision. In this review, the authors discuss applications of these techniques, as well as limitations and possible pitfalls to be avoided in their use.

The authors provide an overview of the uses and limitations of noninvasive brain stimulation techniques such as transcranial magnetic stimulation and suggest ways to advance the field.

This review discusses recent advances in optogenetic pharmacology, discussing its potential to manipulate endogenous neuronal signaling proteins. These approaches include caged agonists and antagonists and reversibly photoswitchable ligands.

Standard light microscopy techniques cannot resolve the subcellular structures of neurons: axons, presynaptic active zones, postsynaptic densities and dendritic spines. In this review, the authors discuss the use of recently developed super-resolution light microscopic techniques to resolve these structures, and how such techniques can be most effectively used in the future.

A study shows that circadian glucocorticoid oscillations have dual roles in dendritic spine plasticity, controlling spine formation and elimination through distinct mechanisms important for motor learning.

Intrahippocampal transplantation of inhibitory interneuron progenitors derived from the medial ganglionic eminence markedly ameliorates the seizure activity and neurobehavioral deficits typically observed in the pilocarpine mouse model of mesial temporal lobe epilepsy, even if the cells are engrafted after the onset of spontaneous seizures.

A study reports that fixation and optomotor responses in Drosophila rely on parallel neural processing of position and motion information, but interact at the behavioral level.

Two studies in this issue report the discovery of different types of uncertainty signals in little-studied, but critical, regions of the forebrain: decision confidence in the pulvinar and reward risk in the anterodorsal septum.

Cognitive function declines as part of the normal aging process. A study finds that the dopamine-boosting drug L-DOPA changes value representation in the brain and improves reinforcement learning in older individuals.

A screen now identifies a protein that regulates degradation of mutant huntingtin, which causes Huntington's disease, and manipulations show that promoting clearance of the toxic protein itself may be sufficient to halt disease.

A study in this issue suggests that neuronal DNA double-strand breaks can result from natural behaviors. The breaks occur in the circuits that are activated and are enhanced in a model of Alzheimer's disease. The implications of this finding are far-reaching.

What makes certain individuals more vulnerable to drug abuse than others? A study finds that potentiation of glutamatergic inputs to nucleus accumbens indirect pathway neurons may protect against compulsive drug-seeking.

In this review, the authors discuss the function of fragile X mental retardation protein (FMRP) in regulating the synthesis of plasticity-related target proteins. The authors review the known mRNA targets of FMRP and discuss the potential therapeutic implications of this research.

A study finds that sound textures are stored in auditory memory as summary statistics representing the sound over long time scales; specific events are superimposed, forming a 'skeleton of events on a bed of texture'.

To be become long-lasting, short-term memories must be transformed into more permanent forms. mTORC2 has now been found to be crucial for the molecular reorganization of the cytoskeleton needed for memory consolidation.

A report suggests that leucine-rich repeat kinase 2 (LRRK2) can be degraded through chaperone-mediated autophagy (CMA) in the lysosome, and several Parkinson's disease–causing LRRK2 mutants impair CMA-mediated selective degradation of cytosolic substrates.