Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOM-ER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric disorders. We further demonstrate that in vivo circHomer1 knockdown (KD) within the OFC can inhibit the synaptic expression of Homer1b mRNA. Furthermore, we show that circHomer1 directly binds to Homer1b mRNA and that Homer1b-specific KD increases synaptic circHomer1 levels and improves OFC-mediated behavioral flexibility. Importantly, double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we uncover an RNA-binding protein that can directly bind to circHomer1 and promote its biogenesis. Taken together, our data provide mechanistic insights into the importance of circRNAs in brain function and disease.

Omphacite is a major mineral phase of eclogite, which provides the main driving force for the slab subduction into the Earth's interior. We have measured the single‐crystal elastic moduli of omphacite at high pressures for the first time up to 18 GPa at ambient temperature using Brillouin spectroscopy. A least squares fit of the velocity‐pressure data to the third‐order finite strain equation of state yields KS0′ = 4.5 (3), G0′ = 1.6 (1) with ρ0 = 3.34 (1) g/cm3, KS0 = 123 (3) GPa, and G0 = 74 (2) GPa. In addition, the synchrotron single‐crystal X‐ray diffraction data have been collected up to 18 GPa and 700 K. The fitting to Holland‐Powell thermal‐pressure equation of state yields KT0′ = 4.6 (5) and α0 = 2.7 (8) × 10−5 K−1. Based on the obtained thermoelastic parameters of omphacite, the anisotropic seismic velocities of eclogite are modeled and compared with pyrolite between 200 and 500 km. The largest contrast between the eclogite and pyrolite in terms of seismic properties is observed between ~310 and 410 km.

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Fetal alcohol spectrum disorders (FASD) are heterogeneous disorders associated with alcohol exposure to the developing fetus that are characterized by a range of adverse neurodevelopmental deficits. Despite the numerous genomics and genetic studies on FASD models, the comprehensive molecular understanding of the mechanisms that underlie FASD-related neurodevelopmental deficits remains elusive. Circular RNAs (circRNAs) are a subtype of long non-coding RNAs that are derived from back-splicing and covalent joining of exons and/or introns of protein-coding genes. Recent studies have shown that circRNAs are highly enriched in the brain, where they are developmentally regulated. However, the role of the majority of brain-enriched circRNAs in normal and pathological brain development and function has not been explored yet. Here we carried out the first systematic profiling of circRNA expression in response to prenatal alcohol exposure (PAE) in male and female embryonic day 18 (E18) whole brains. We observed that the changes in circRNA expression in response to PAE were notably sex-specific and that PAE tended to erase most of the sex-specificity in circRNA expression present in control (saccharin-treated) mice. On the other hand, RNA sequencing (RNA-seq) in the same samples showed that changes in protein-coding gene expression were not predominantly sex-specific. Using circRNA quantitative real-time PCR (qRT-PCR), we validated that circSatb2 , which is generated from the special AT-rich sequence-binding protein 2 ( Satb2 ) gene, is significantly upregulated in the brain of E18 male PAE mice. We also show that circPtchd2 , a circRNA synthesized from dispatched RND transporter family member 3 ( Disp3 , also known as Ptchd2 ), exhibits significantly higher expression in E18 control but not PAE female mouse brain relative to males. Taken together, our results demonstrate that PAE differentially alters circRNA expression in the developing brain in a sex-specific manner.