Research articles

The authors use developmental changes in chromatin accessibility to identify thousands of enhancer elements that are active at different postnatal developmental stages in granule neurons of the cerebellum. Zic transcription factors were found to promote gene expression patterns key for neuronal maturation by binding to late-acting enhancer elements.

Hormone-induced brain masculinization occurs during a perinatal sensitive period but endures into adulthood. Researchers explored DNA methylation as a candidate mechanism. Methylation is higher in female brain and suppresses masculinization genes, which are liberated by hormone-induced reductions in DNMT activity in males. Pharmacological inhibition of DNMTs reduces methylation, masculinizes female brain and behavior and reopens the sensitive period.

Socioeconomic status is associated with cognitive development, but the extent to which this reflects neuroanatomical differences is unclear. In 1,099 children and adolescents, family income was nonlinearly associated with brain surface area, and this association was greatest among disadvantaged children. Further, surface area mediated links between income and executive functioning.

Furutachi et al. identified a slowly dividing subpopulation of embryonic progenitors that later gives rise to most adult neural stem cells (NSCs) in the subependymal zone. Moreover, they found that p57 is responsible for the slow cell cycle of this embryonic population and acts causally in the emergence of adult NSCs.

Processing multiple sensory modalities is critical for executing complex behaviors. This study finds that single cerebellar granule cells integrate inputs from both vestibular and visual input pathways, each exhibiting characteristic synaptic strengths and plasticities. These are translated into output dynamics that enhance the network's representation of complex sensory contexts.

DISC1 is believed to be a genetic risk factor for schizophrenia, but its pathophysiological functions are not fully understood. Using proteomics, Tsuboi et al. identify several RNA-binding proteins, including HZF, as DISC1 interactors and reveal that DISC1, together with HZF, regulates the dendritic transport of ITPR1 mRNA to modulate synaptic plasticity.

The authors show that chronic neonatal hypoxia reduces GABA_A receptor–mediated signaling to oligodendrocyte precursor cells in the cerebellar white matter and enhances their proliferation, delays oligodendrocyte maturation and disrupts myelination. Following hypoxia, treatment with a GABA uptake blocker restores myelination.

The authors show that haploinsufficiency of TBK1 causes familial forms of the neurodegenerative diseases ALS and FTD. Loss of binding of a TBK1 protein interaction domain to optineurin, a protein previously linked to ALS, is sufficient to cause the disease. Both proteins regulate autophagy and inflammation.

Although it has been widely hypothesized that decisions can be guided by mental simulation of their likely consequences, there has not been direct evidence linking prospection to choices. Here, using fMRI, the authors show that neural representation of future outcomes is related to the choices that participants make.

The relationship between EEG oscillations and underlying neural activity is unclear. The authors find a U-shaped relationship between the two in visual cortex that is linked to visuospatial attention performance in monkeys. A neural network model indicates a critical role for selective inputs to inhibitory neurons.

Forgetting can at times serve an adaptive purpose. Here the authors develop a method for dynamically tracking neocortical activity patterns related to the retrieval of individual episodic memories. They show that remembering gradually enhances relevant memories but also suppresses the cortical traces of interfering memories, causing adaptive forgetting.

Expression of TET1 dioxygenase, which catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, is downregulated by repeated cocaine administration in mouse nucleus accumbens, where it controls cocaine reward. Genome-wide mapping of 5-hydroxymethylcytosine in this brain region reveals novel modes of epigenetic regulation by cocaine.

Using a quantitative perfusion imaging technique, the authors investigated in healthy humans what brain regions encode a slowly varying tonic pain state. Only a small region in the contralateral dorsal posterior insula tracked the full pain experience, suggesting it is the homolog of a nociception-specific region found in animals.

This study shows how somatostatin (SOM)-expressing interneurons contribute to odor coding in mouse olfactory cortex. Odor-tuned SOM cells regulate neuronal output through a purely subtractive operation that is independent of odor identity or intensity. This operation enhances the salience of odor-evoked activity without changing cortical odor tuning.

The authors used rewarding stimulations triggered by place cell activity during sleep to create a place preference for the related place field in mice once they woke up. This shows that an explicit memory trace can be created during sleep and demonstrates a causal role of place cells in spatial navigation.

The authors demonstrate that the anti-stress peptide neuropeptide Y reduces binge drinking in monkeys and mice by inhibiting neurons in the amygdala that contain the stress peptide corticotropin-releasing factor. Further, the authors find that chronic drinking leads to changes in anti-stress peptide systems that may underlie the pathology stemming from binge drinking.

The developing human cortex contains diverse populations of neural progenitor cells, including a large proportion of outer radial glia (ORG), a progenitor type that is rare in the mouse. The authors identify a transcriptional signature of ORG characterized by markers of neuronal lineage fate and use single-cell analyses to contrast the heterogeneity of cortical progenitors across human, mouse and ferret.

This study utilizes in vivo clonal lineage tracing of adult subependymal zone neural stem cells in mice to reveal frequent stem cells divisions and significant progeny expansion, thus allowing rapid clonal growth. The authors also show that neural stem cells lacked significant long-term self-renewal abilities which led to clonal exhaustion. Olfactory bulb neuronal diversity emerges at the population level, as single stem cells show restricted diversity in neuronal subtype production.

The authors use computational modeling of participants' performance on an aversive learning task to examine how decision-making is altered in anxiety. Results indicate that anxious individuals struggle to use information regarding the stability of action-outcome relationships to guide their choices. Pupillometry data link this deficit to altered norepinephrinergic function.

Ling and colleagues report evidence for orientation selective responses in the human lateral geniculate nucleus (LGN). Moreover, they found that the nature of these orientation representations depend on attentional feedback, suggesting that the LGN serves as an early filter for sensory information, altering contour signals before they reach cortex.