News & Views in 2018

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.

In 2010, Johnson and Kenny provided conclusive evidence that extended access to a Western-style diet promotes addictive-like behavior in rats by downregulating D₂ receptors while promoting obesity. This focused attention on the parallels between drug addiction and overeating and fueled a decade of food addiction research.

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.

Landmark papers in 2005 and 2009 provided the first evidence of links between development, training, and white-matter plasticity in humans, contributing to a shift in our understanding of brain wiring that has inspired fundamental research into the role of genes, the environment, and the mechanisms underlying training-related plasticity.

In an unfamiliar situation, animals display variable choice behavior. Based on computational modeling and empirical data, a new study suggests that the variability in decision-making across individuals is driven by differences in internal neural dynamics in the medial frontal cortex.

The combination of spinal epidural stimulation and physical therapy is restoring walking function to people with spinal cord injury. With intensive rehabilitation, some participants are able to walk in their communities during stimulation and even regain control over previously paralyzed movement in the absence of stimulation.

Two recent studies have expanded our understanding of the circuits controlling urination: one described a projection from brainstem to spinal cord that relaxes the urethral sphincter, and the other revealed a subpopulation of brainstem-projecting layer 5 pyramidal neurons in primary motor cortex that direct the initiation of urination.

What you choose depends on what information your brain considers and what it neglects when computing the value of actions. An early theory used this insight for a computational account of habits versus deliberation. It has ultimately helped uncover how choice in the brain goes beyond such simple dichotomies.

A new theory derives the sequential nature of hippocampal replay from first principles and, moreover, predicts the specific patterns of replay that are actually observed in multiple different experiments.

In this issue of Nature Neuroscience, Menegas et al. demonstrate a role for midbrain dopamine neurons projecting to the tail of the striatum in encoding stimulus novelty and threat avoidance. From this study emerges a model whereby distinct dopaminergic projections to striatum influence behavior along at least two axes, one representing value and one representing threat.

While the role of protein synthesis in synaptic plasticity and memory is well-established, protein degradation processes have been less studied. A seminal 2003 Nature Neuroscience paper showed that ubiquitin-dependent degradation of synaptic proteins is engaged during activity-regulated synaptic remodeling.

How we value our own rewards depends on what others have. A new study shows that neurons in the medial prefrontal cortex selectively monitor the value of rewards received by oneself or by another individual, whereas midbrain dopaminergic neurons integrate these values to generate social subjective reward values.

The surge in single-cell and single-nucleus RNA-sequencing has raised the question of the value of bulk tissue transcriptomics. Kelley et al. describe an analysis framework by which existing bulk transcriptomic data can be reanalyzed using cell-type-specific data to yield insights into cell-type variation across brain regions and diseases.

Twenty years ago, 2 studies showed that behavioral experience affects proliferation & survival of newborn neurons in adult hippocampus, suggesting adult neurogenesis as a form of experience-dependent neuroplasticity relevant to memory, emotion, & mental health.

A study has found that young male mice with a mutation of the autism-associated gene Chd8 show abnormal behaviors and elevated neuronal activation in several brain areas under stressful conditions, while female mice with the same mutation have reduced baseline neuronal activity, which may protect them from developing these abnormal phenotypes.

A deep-learning-based software package called DeepLabCut rapidly and easily enables video-based motion tracking in any animal species. Such tracking technology is bound to revolutionize movement science and behavioral tracking in the laboratory and is also poised to find many applications in the real world.

Heterogeneity of function in microglia from different brain regions is suspected but largely unknown. This paper identifies the epigenetic mechanism underlying differential phagocytic activity of microglia in discrete brain regions and examines the consequences of inducing an appetite not commensurate with the level of cell death in the region in which they reside.

In the 20th century we thought the brain extracted knowledge from sensations. The 21st century witnessed a ‘strange inversion’, in which the brain became an organ of inference, actively constructing explanations for what’s going on ‘out there’, beyond its sensory epithelia. One paper played a key role in this paradigm shift.

Phenotypic diversity confers the benefits of adaptation to an evolving species. Random perturbations in our genetic structure may result in new functions required for some change in our environment, and we can survive outside of our happy niche for generations. But where are the limits on this sort of diversity?

Protein kinases are key regulators of excitatory synapse plasticity. In this issue, using novel optical reporters of protein kinase C (PKC) activity, Colgan et al. identify PKCα as critical for integrating NMDA receptor and neurotrophin signaling to control dendritic spine structural plasticity, synaptic potentiation, and learning and memory.