Resources in 2015

The authors applied a correlation-based metric, ‘differential stability’ (DS), to assess reproducibility of gene expression patterning across individual brains, revealing mesoscale genetic organization. The highest DS genes were enriched for brain-related biological annotations, disease associations and drug targets, and their anatomical expression pattern correlated with resting state functional connectivity.

The authors performed a comprehensive proteome analysis of the adult mouse brain, its major regions and CNS cell types at a depth of >13,000 proteins. This new resource represents the largest collection of cell type–resolved protein expression data of the brain. The power of the data set was illustrated by identifying novel adhesion molecules in glia and neuron interaction.

The authors used trans-synaptic tracing to examine and compare circuit anatomy in mouse barrel and medial prefrontal cortex, revealing novel organizational features and contrasts between the two areas. Notably, medial prefrontal layer 5 neurons receive more long-distance inputs and more local inhibitory inputs than layer 5 neurons in barrel cortex.

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.

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.

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 discovered that circular RNAs are significantly enriched in the mouse brain and can be visualized in situ, near synapses. They observed that many circRNAs change their abundance during synaptogenesis and also following neuronal homeostatic plasticity, suggesting a function for circRNA in regulating synaptic development and plasticity.