Volume 18 Issue 8, August 2015

How do neurons combine distinct information streams and form long-lasting associations? Dendritic plateau potentials may allow the integration and storage of coincident location and contextual information in hippocampal neurons.

Imaging experiments in awake mice reveal striking, circuit-specific synaptic structural remodeling of inhibitory axons during learning.

The confidence that we place in our decisions can affect the judgments themselves. The BOLD signal in ventromedial prefrontal cortex automatically reflects the relationship between confidence and judgments on a range of tasks.

The nature of the retinal computations of the direction of motion of visual stimuli has fascinated vision researchers for decades. In this Review, Borst and Helmstaedter discuss the most recent findings in the field, and draw parallels and point to differences in the circuitry of the mouse retina and the fly optic lobe from which such basic neuronal computation arises.

The authors show that changes in nuclear dynamics of p75^NTR by γ-secretase cleavage are a novel molecular switch that determines TGF-β signaling in astrocytes. Cleaved p75^NTR acts as a component of the nuclear pore complex, regulating nuclear import of Smad-2 in astrocytes. The authors find that p75^NTR is required in mice for TGF-β-induced glial scar formation and reduced neuronal activity.

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.

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.

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.

The authors used chronic two-photon calcium imaging to record activity in primary whisker somatosensory cortex neurons projecting to secondary somatosensory or primary motor cortex while mice learned a texture discrimination task. Learning-related changes in primary somatosensory cortex enhanced sensory representations in a pathway-specific manner and provided downstream areas with task-relevant information for behavior.

This study identifies opposite changes in two main subtypes of inhibitory neurons in the mouse motor cortex during motor learning. With learning, the number of synapses made by somatostatin-expressing inhibitory neurons (SOM-IN) onto the distal dendritic branches of pyramidal neurons decreased, whereas the number of perisomatic contacts made by parvalbumin-positive cells increased. The authors also found that optogenetic disruption of SOM-IN activity resulted in impairment of learning-related dendritic spine reorganization and motor learning.

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.

Specialized cell types in the medial entorhinal cortex (MEC), such as grid cells, are thought to provide spatial information to the hippocampus. Here the authors show that MEC lesions disrupt hippocampal theta phase precession, which suggests that the MEC is critical for cognitive functions that depend on precisely timed neuronal activity.

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.

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.

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.

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.

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.

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.