Research articles

By recording from cerebellar output neurons during motor learning, the authors provide direct evidence for an elegant computation requiring the comparison of predicted and actual sensory feedback to signal unexpected sensation. Their results suggest that rapid updating of the cerebellum's internal model enables the brain to learn to expect unexpected sensory input.

The authors show that fruit flies briefly silence visual processing during voluntary flight turns, which likely helps flies to ignore the image of the world sweeping over the retina during such turns.

The authors report that the ultrastructure and plasticity of excitatory synapses connecting dentate gyrus and CA3 of the hippocampus are severely compromised in a transchromosomic mouse model of Down syndrome. These alterations are accompanied by unstable information coding by CA3 and CA1 place cells, which may contribute to aspects of impaired cognition in the disease.

Humans learn about people and objects through positive and negative experiences, yet they can look beyond rewards to encode trait-level attributes such as generosity. The authors show that neural activity and choices reflect feedback-based learning about rewards and traits of people and slot machines and that trait learning strongly drives decisions about new social interactions.

It is widely assumed that D1 and D2 dopamine receptor-expressing striatal neurons code for discrete pathways in the basal ganglia. Combining optogenetics and electrophysiology, the authors show that this output architecture does not apply to nucleus accumbens neurons. Current thinking attributing D1/D2 selectivity to accumbens projections thus should be reconsidered.

Humans have a capacity for hierarchical cognitive control—the ability to simultaneously control immediate actions while holding more abstract goals in mind. The authors show that neural oscillations establish dynamic communication networks within the frontal cortex and that these oscillations coordinate local neural activity with increasing cognitive control.

The authors show that the neuron-specific LSD1 variant (LSD1n) promotes transcription initiation and elongation in response to neuronal activity. LSD1n is essential for spatial learning and long-term memory formation. LSD1n exhibits novel substrate specificity for histone H4 K20 methylation.

To elucidate novel molecular mechanisms underlying neurodegeneration in Parkinson's disease, the authors generated mice for cell type-specific profiling of dopaminergic neurons. Regulatory network analysis of translatome libraries from dopaminergic neurons under degenerative stress facilitated the identification of intrinsic upstream regulators that oppose degeneration. This strategy can be generalized to investigate degeneration of other classes of neurons.

Using a combination of electrophysiological and neurochemical techniques the authors report that deep and superficial CA1 pyramidal neurons behave differently during hippocampal sharp-wave ripples, with deep cells becoming hyperpolarized and superficial cells undergoing depolarization. The study also reveals some of the microcircuit mechanisms that underlie this spatiotemporal specialization, including the involvement of CA2 pyramidal cells and the role of perisomatic inhibition.

Evidence suggests that aberrant RNA processing contributes to amyotrophic lateral sclerosis (ALS). Using RNA sequencing, Prudencio et al. assessed the extent of transcriptome defects in C9orf72-associated (c9ALS) and sporadic ALS (sALS) brains. They report extensive defects in expression, alternative splicing and alternative polyadenylation that are significantly distinct between individuals with c9ALS and sALS.

Abnormal post-translational modifications of tau may contribute to Alzheimer's disease, but normal tau modifications are poorly understood. Using advanced mass spectrometry, a great variety of modifications were identified on endogenous mouse tau. Tau appears to be highly regulated and may fulfill diverse functions, most of which remain to be defined.

The ventromedial prefrontal cortex has been identified as a key node for judging the pleasantness of various situations. In a series of fMRI experiments, Lebreton and colleagues demonstrate that the same brain region also computes an implicit representation of confidence, defined as an estimate of judgment accuracy.

Changes in cAMP signalling in the brain influence mood and responses to stress. Here, the authors found that Cdk5 regulates cAMP degradation by PDE4 phosphodiesterases in the mouse ventral striatum. Targeting this mechanism in striatum or D1 dopamine receptor–expressing neurons improved behavioral responses to acute and chronic stressors. These results suggest an alternative strategy for the treatment of mental illnesses like depression where stress is a risk factor.

By examining the activity of layer 2/3 excitatory neurons in the mouse primary visual cortex, the authors demonstrate that learning enhances the relative impact of top-down processing by the retrosplenial cortex while reducing the influence of the bottom-up stream from layer 4 excitatory neurons. This effect is partially mediated by somatostatin-expressing inhibitory neurons.

Identifying enhancers regions has been primarily focused on model organisms and human transformed cell lines. This study characterizes enhancer RNA (eRNA) expression in the human brain by identifying brain region–specific eRNAs and assessing eRNA-gene coexpression interactions. The authors further demonstrate an enrichment of brain eRNAs for autism-associated genetic variants.

The authors found that dendritic plateau potentials, resulting from the conjunction of EC3 and CA3 inputs, positively modulate existing place fields and induce novel place field formation in CA1 pyramidal neurons. Such a canonical circuit operation may support the formation of spatial maps in the hippocampus and the acquisition of feature selectivity elsewhere in cortex.

The molecular mechanisms underlying the regulation of dopamine transporter activity in the brain remain poorly understood. The authors show that glial cell line–derived neurotrophic factor, its receptor Ret and the Rho family GEF protein Vav2 are required for modulating dopamine transporter cell surface expression and transporter activity in the nucleus accumbens.

Intelligent behavior demands coordination among the multiple forms of spatial representation generated in distinct neural structures. Here, Alexander and Nitz show that retrosplenial cortex neuron ensembles conjunctively encode progression through routes, environmental position, and the actions of the animal. Thus, the region may serve as a critical interface between brain regions generating different forms of spatial mapping.

A large literature has demonstrated the important role of spinal microglia in chronic pain processing. This paper demonstrates that microglia are required in male but not female mice. In female mice, a similar function appears to be subserved by adaptive immune cell, likely T lymphocytes.

Individuals must compensate for their motor uncertainty—that is, the discrepancy between intended movement and actual. Here, the authors measured the subjective error representation used in planning reaching movements and found that, while the objective motor error was uni-modal, near-Gaussian, subjective distributions were typically multimodal. This suggests a flexible strategy for computing with uncertainty across many different sorts of problems.