Volume 22 Issue 8, August 2019

Misfolded protein aggregates are a classical hallmark of many neurodegenerative diseases. By combining a mouse model of misfolded protein injection and a brain network model of misfolded protein diffusion, a study now finds a strong link between the stereotypical spreading patterns of neurodegeneration, protein expression and anatomical connectivity.

On April 13, the neuroscience community lost a remarkable scientist and true humanitarian. Paul Greengard, co-recipient of the Nobel Prize in Physiology or Medicine in 2000, Vincent Astor Professor and head of the Laboratory of Molecular and Cellular Neuroscience at the Rockefeller University in New York City, died of an apparent heart attack at age 93. Paul will be remembered for his seminal contributions to neuroscience, for pioneering the field of neuronal signal transduction and for training hundreds of neuroscientists. For anyone who knew Paul it will come as no surprise that up until a few hours before his death, Paul was doing what he liked the best: working on a scientific manuscript.

There is disagreement on how best to define and investigate fear. Nature Neuroscience asked Dean Mobbs to lead experts from the fields of human and animal affective neuroscience to discuss their viewpoints on how to define fear and how to move forward with the study of fear.

A new study reveals that complete loss of TREM2 function or expression of the TREM2^R47H Alzheimer’s disease risk variant hinders amyloid-β plaque-associated microglia, leaving peri-plaque neurites susceptible to tau seeding and spreading.

Guo et al. show that synaptic alterations in ACC pyramidal neurons underlie social impairments in Shank3 mutant mice and that selective activation of ACC pyramidal neurons or enhancing AMPAR function improves social behavior in these mice.

This paper elucidates the mechanism regulating the subcellular localization of UBE3A and demonstrates that abrogation of UBE3A nuclear localization leads to electrophysiological and behavioral impairments in mice and to Angelman syndrome in humans.

Henderson et al. use quantitative pathology mapping and network modeling to show that α-synuclein pathology spreads through a neuroanatomically connected network, guided by selective vulnerability and genetic risk factors.

SFRP1, an ADAM10 inhibitor, is elevated in the brains of patients with Alzheimer’s disease (AD). Antibody-mediated neutralization of its activity stalls brain alterations and cognitive loss in AD-like mice, supporting SFRP1 as a potential target for disease therapy.

Chondroitinase injections into monkey spinal cords 4 weeks after hemisection injury increased corticospinal axon growth and corticospinal synapse formation and improved functional outcomes.

T cell-derived interferon-γ signaling to microglia underlies spatial-learning deficits associated with West Nile virus and Zika virus via the loss of hippocampal presynaptic termini or neurons with elimination of postsynaptic termini, respectively.

Genetic techniques to manipulate autonomic nerves in a tumor- and fiber-type-specific manner in rodent models of breast cancer reveal that sympathetic nerve denervation or parasympathetic nerve stimulation suppresses breast cancer growth and progression.

The authors find that olfactory bulb inputs and outputs sample overlapping but distinct odor subspaces. Physical–chemical properties used to characterize odorants are not well represented in bulb activity, urging further search for better descriptors of odor space.

Badwan et al. find direction-opponent responses in the most peripheral direction-selective cells of Drosophila. They analyze how this property constrains models for direction selectivity and how it impacts motion estimation in natural scenes.

Parietal neurons encode the information gains that saccades are expected to bring for subsequent actions independently of economic utility, consistent with a boost in neural gain to facilitate the implementation of sampling policies.

People often remember visual information over brief delays while also seeing new images in their immediate visual surroundings. Areas of the brain known to process visual information are shown to juggle these memory and sensory demands.

Targeting genes to specific cell types is valuable for basic science and gene therapy. The authors describe a collection of AAVs containing synthetic promoters targeting a broad range of neuronal cell types in mice, non-human primates and humans.

Sun et al. built a comprehensive atlas of inputs to major types of GABAergic interneurons in the prefrontal cortex of mice. Through three-dimensional reconstruction of neural morphology, the authors classified input neurons and identified novel neural circuits.

Using a large task battery spanning motor, cognitive, social and affective domains, this functional MRI (fMRI) study provides a comprehensive functional map of the human cerebellum, along with a comparison to maps derived from anatomy and resting-state fMRI data.