Volume 22 Issue 1, January 2019

TDP-43 forms cytoplasmic aggregates in degenerating neurons of frontotemporal dementia (FTD) patients. Laferrière et al. now establish that TDP-43 assemblies from distinct FTD subtypes have different structures, neurotoxicities, and seeding activities, which correlate with FTD severity. Thus, distinct pathological TDP-43 assemblies akin to prion strains might underpin distinct FTD subtypes.

The locus coeruleus is known to be an essential source of neuromodulation that influences sensory processing, including the enhancement of feature selectivity associated with attentional focus. A new study shows that the primary sensory thalamus encompasses one circuit that underlies this enhancement.

Knowledge of the role of glial–neuronal interactions in the physiology of food intake and energy metabolism is emerging. This review highlights the role of astrocytes, microglia, and tanycytes in central control of systemic metabolism.

A satisfactory understanding of how natural stimuli are encoded by neural circuits has remained elusive. Advances in machine learning provide new approaches to this problem by merging constraints imposed by stimulus statistics and behavioral goals.

An overall downregulation of RNA editing was observed in postmortem brains from people with autism, which was consistent across brain regions and genetic disorder subtypes. These changes were regulated by the RNA-binding proteins FMRP and FXR1P.

Tau but not amyloid-beta pathology is associated with widespread alterations of histone 3 lysine 9 acetylation in the aged human cortex. Similar alterations of chromatin organization occur in iPSC-derived neurons after overexpression of tau.

Neuron types vulnerable to tau accumulation (excitatory neurons) in AD brain are intrinsically less able to maintain tau homeostasis than neuron types that are resistant (inhibitory neurons).

Microscopic imaging of neurons in mouse models of Alzheimer’s disease shows that plaques increase activity while neurofibrillary tangles suppress activity. The combination of plaques and tangles, as in humans with Alzheimer’s disease, suppresses activity.

Using a newly developed biochemical method for aggregated protein extraction, Laferrière and colleagues uncover different neurotoxic types of pathologic TDP-43 assemblies in the brains of subjects with distinct subtypes of frontotemporal dementia.

Single-cell mass cytometry was applied to comprehensively characterize postmortem and fresh human microglia. Using a hybrid workflow for multidimensional data analysis, a core signature and regional heterogeneity were identified.

CD133 and Notch1 double-positive GSCs were preferentially located along Jagged1-expressing white matter tracts, which exhibited a demyelinated phenotype. The NOTCH1–SOX9–SOX2 positive-feedback loop controls GSC invasion along white matter tracts.

Yu, Li et al. show that VTA GABA and glutamate neurons induce sleep and waking, respectively, via projections to the lateral hypothalamus and nucleus accumbens. Thus, in addition to influencing reward-directed behaviors, the VTA regulates arousal.

Locus coeruleus (LC) activation enhanced thalamic feature selectivity & perceptual performance. Electrophysiology and modeling suggest this improvement is due to reduction in Ca²⁺ T-channel activity by LC regulation of intrathalamic circuit dynamics.

Polanía et al. show that, similarly to sensory signals, subjective preferences guiding choice are represented by the brain in a manner that accounts for regularities of the environment, thereby optimizing use of limited neural processing resources.