Volume 22 Issue 2, February 2019

Experience unfolds continuously in time, but we remember discrete sequences of events. In this issue of Nature Neuroscience, Montchal et al. describe brain activity patterns that predict how well people remember precisely when recent events occurred. Converging evidence suggests that homologous neural machinery structures temporal representations in rats and people.

Volterra et al. review evidence that astrocyte-generated signals participate in recruitment and function of neuronal networks underlying memory performance and that signal abnormalities under pathological conditions contribute to cognitive impairment.

Klim et al. illuminate pathomechanisms of ALS using pluripotent stem cells to identify transcripts altered in human motor neurons by perturbations to ALS protein TDP-43, finding the microtubule regulator STMN2 highly sensitive to TDP-43 malfunctions.

The mRNA encoding stathmin-2, a protein implicated in axonal growth, is shown to be widely suppressed by premature polyadenylation in both sporadic and C9orf72 ALS through a mechanism directly dependent on loss of nuclear TDP-43 in motor neurons.

Loss of Trem2 function increases early amyloidogenesis by preventing microglial activation and clustering around amyloid seeds. As a consequence of reduced microglial ApoE production in the absence of Trem2 function, amyloid plaques contain less ApoE.

Zhou et al. show that NCORs regulate memory and synaptic plasticity through a GABAergic hypothalamus–hippocampus projection in mice, and that variants in NCOR1 and NCOR2 are linked to intellectual disability and neurodevelopmental defects in humans.

The authors describe a local population of GABAergic neurons that directly inhibits locus coeruleus noradrenergic neurons. They show how this circuit regulates arousal gain and tone.

Shao et al. report that interneurons derived from iPSCs from schizophrenia patients have altered protocadherin expression and synaptic and arborization deficits. A PKC inhibitor, acting downstream of protocadherin, reversed the arborization deficit.

Using a dynamic time-course approach to model developmental trajectories in autism spectrum disorder, Schafer et al. identified aberrant gene network dynamics as a part of an ongoing process that is primed early in development.

Lieder et al show that individuals with dyslexia and individuals with ASD rely mostly on recent and earlier perceptual information, respectively, during perceptual tasks. This may explain the unique difficulties associated with the two conditions.

Concurrently recording neural spiking across cortical layers in a medial frontal area with EEG reveals the microcircuitry of error and reward signals, showing how neural circuits can realize executive control and produce error-related negativity.

Two qualitatively different neural mechanisms for maintaining information in short-term memory, experimentally observed in animal studies, emerge as part of a spectrum of solutions in recurrent neural networks trained on short-term memory tasks.

In the lateral entorhinal cortex, high-precision judgments related to timing were associated with greater blood-oxygen-level-dependent fMRI activity than low-precision time judgments. This brain region may be involved in memory for when events occur.

Neuronal activity across task states converges onto a low-dimensional manifold. Flow within this attractor space covaries with network-level topology, fluid intelligence, and regional differences in the density of neuromodulatory receptors.

Prefrontal cortex can be flexibly engaged in many different tasks. Yang et al. trained an artificial neural network to solve 20 cognitive tasks. Functionally specialized modules and compositional representations emerged in the network after training.

An extensive profile of DNA methylation in neuronal and non-neuronal cells across four brain regions is reported, showing that differential epigenetic marks are enriched for DNA variants associated with neuropsychiatric traits.

A nanobody-based immunolabeling method, vDISCO, boosts the signal of fluorescent proteins and allows imaging of subcellular details in intact transparent mice. It uncovers neuronal projections and skull–meninges connections in whole adult mice.