Volume 20 Issue 9, September 2017

Hexanucleotide repeat expansions in C9orf72 gene locus create double jeopardy, first by leading to DNA–RNA R-loops that spawn double-strand breaks and second by the synthesis of dipeptide repeats that hinder DNA repair. This two-pronged mechanism may explain neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia.

What is the basis for the feeling that someplace or someone is familiar? Molas et al. have identified brain structures involved in signaling familiarity, a necessary element for the expression of preference for novelty.

A study introduces innovative ways to test whether neural population activity exhibits structure above and beyond that of its basic components.

Hattori et al. review the recent advances in our understanding of the roles of inhibitory neuron subtypes in shaping the activity and plasticity states of neocortical circuits, how neuromodulators control inhibitory neuron subtypes, and the role of inhibitory neuron dysfunction in neurological disorders.

Zika virus infection is associated with neurological disorders, yet few studies have directly examined its impact on the peripheral nervous system. Oh et al. show that Zika virus can infect peripheral neurons in the mouse in vivo, as well as human peripheral neurons in vitro, leading to increased cell death and transcriptional dysregulation.

Recent evidence supports a functional connection between gut microbiota and the nervous system. Here the authors show that gut microbiota plays a critical role in the development of chemotherapy-induced pain. This role of the microbiota is likely mediated, in part, by Tlr4 expressed on hematopoietic cells, including macrophages.

Survey of postzygotic mosaic mutations (PZMs) in 5,947 trios with autism spectrum disorders (ASD) discovers differences in mutational properties between germline mutations and PZMs. Spatiotemporal analyses of the PZMs also revealed the association of the amygdala with ASD and implicated risk genes, including recurrent potential gain-of-function mutations in SMARCA4.

An expanded repetition of a DNA sequence within the C9orf72 gene is the most common genetic cause for motor neuron disease and frontotemporal dementia. In this study, the authors show that this expansion causes increased genomic breaks and reduces the cell's ability to repair the breaks, ultimately leading to neuronal cell death.

The mechanisms underpinning neuronal death in Alzheimer's disease (AD) remain unclear. Caccamo and colleagues show that necroptosis contributes to neurodegeneration in AD. Blocking necroptosis reduced neuronal loss in a mouse model of AD, suggesting that necroptosis might be a therapeutic target in AD.

Antipsychotic treatment in patients with schizophrenia often reduces hallucinations and delusions, but cognitive deficits that impair performance of everyday activities may persist or worsen. Our findings reveal a mechanism by which increased NF-κB activity leads to increased HDAC2 levels, impairing synaptic plasticity and memory during prolonged antipsychotic treatment.

The mechanistic basis of how novel stimuli become familiar with repeated exposures has remained elusive. Molas et al. demonstrate that familiarity activates the interpeduncular nucleus, thereby reducing motivation to explore. Familiarity signaling in the interpeduncular nucleus is bidirectionally modulated by habenula and ventral tegmental area afferents to control novelty preference.

Although the hippocampus has long been linked to planning, it has not been shown to be necessary for planning behavior. Using computational modeling and a new rat task that allows the quantification of planning behavior across many repeated trials, the authors report the first evidence that hippocampal inactivation impairs planning.

A fundamental goal of learning is to establish neural patterns that cause desired behaviors. This paper demonstrates that sleep-dependent processing is required for credit assignment and the establishment of task-related activity reflecting the causal neuron-behavior relationship. Decoupling of spiking to sleep slow oscillations using optogenetics methods disrupted this process.

Yates and colleagues statistically dissect MT and LIP responses during motion discrimination. They show decreasing temporal weighting of motion in MT, consistent with psychophysical weighting, and show that LIP spikes encode the upcoming choice more than integrated motion or simultaneously recorded MT spikes, suggesting an indirect relationship between these areas.

The authors address why the use of prior expectations might be compromised in autism, by using computational models and pupillometric markers of the neuromodulator noradrenaline. They show that by estimating the world to be more changeable than it really is, adults with autism have difficulty in learning what to expect.

Korin et al. use CyTOF mass cytometry to characterize immune cell populations in the naive mouse brain (parenchyma, choroid plexus and meninges). This single-cell analysis of cell-surface proteins reveals the presence and phenotype of distinctive immune populations in the mouse brain compartment.

To what extent are population-level results an expected byproduct of simpler structure already known to exist in single neurons? Conventional controls are insufficient to perform this critical investigation. The authors developed a methodological framework to test the significance of population-level studies and apply it to prefrontal and motor cortices.