Non-coding variants in the human MIR137 gene locus increase schizophrenia risk at a genomewide significance level. However, the functional consequence of these risk alleles is unknown. Here, we examined induced human neurons harboring the minor alleles of four disease-associated single nucleotide polymorphisms (SNPs) in MIR137, and observed increased MIR137 levels compared to major allele-carrying cells. We found that miR-137 gain-of-function causes downregulation of the presynaptic target genes, Complexin-1 (Cplx1), Nsf, and Synaptotagmin-1 (Syt1), leading to impaired vesicle release. In vivo, miR-137 gain-of-function results in changes in synaptic vesicle pool distribution, impaired mossy fiber-LTP induction and deficits in hippocampus-dependent learning and memory. By sequestering endogenous miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement of Syt1 expression partially restored synaptic plasticity, demonstrating the importance of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by which miR-137 dysregulation can impair synaptic plasticity in the hippocampus.

Single crystals of the filled skutterudite compound ThFe 4 As 12 were examined down to T = 0.4 K and in magnetic fields up to B = 9 T. Electron transport properties combined with results of Hall-effect measurements indicate semimetallic properties with a charge carrier density of the order of 2 × 10 20 cm-3. In terms of a two-band model, the effective mass of the electrons is nearly a factor of 5 larger than the hole effective mass. A small carrier density is in line with the lack of magnetic ordering in this Fe-based filled skutterudite. Therefore, a Sommerfeld coefficient of the electronic specific heat of 45 mJmol-1 K-2 for semimetallic ThFe 4 As 12 is an unexpected observation whose origin remains to be explained.

Ability to efficiently extinguish fear memories is critical for individual well-being, and extinction impairments are commonly observed in a variety of neuropsychiatric conditions. Efficient extinction is also a critical component of exposure therapy, the most widely utilized form of treatment for anxiety and trauma/stressor-related disorders. While individual as well as sex-related differences in extinction are recognized, their neurobiological underpinnings remain unclear. To examine neurobehavioral and molecular features that may contribute to the efficacy of fear memory extinction in genetically similar subjects raised in the same conditions, extinction learning was analyzed in the cohorts of inbred wild-type male and female mice. We showed that unlike memory acquisition, anxiety status of the animals appeared to significantly influence extinction. Interestingly, the effect was sex-specific: the level of anxiety-related behavior inversely correlated with extinction efficacy in male mice only. Significant difference in hippocampal expression of anxiolytic Corticotropin Releasing Hormone Receptor 2 (CRHR2) between the male, but not female animals differing in extinction efficacy, suggests that CRHR2 may serve as a key factor underlying sexually dimorphic interplay between anxiety and fear memory extinction. Our results emphasize the need for tailoring treatment strategies for anxiety and fear-related disorders in accordance with the patient sex and identify specific neurobehavioral and molecular features potentially important for such adjustments.

In the known topological semimetals, conventional charge carriers exist in addition to relativistic quasiparticles, and thus a disentangling of their conduction properties remains challenging. Here, we address an unsaturated extreme magnetoresistance (XMR) with a marked deviation from the semiclassical B 2 behavior that is commonly credited to the presence of topologically protected electronic states. For the topologically trivial semimetal LuAs, we observe a nonsaturating XMR with a nonquadratic magnetic-field dependence gained up to nearly 60 T. Remarkably, this diamagnetic material exhibits a very large magnetostriction that provides solid evidence for a field-dependent variation of electron and hole concentrations. We show that an underlying strain-induced change in the charge-carrier densities can give rise to an unsaturated XMR even in a moderately imbalanced semimetal. Our finding is of importance as well for topological semimetals in which the number of conventional charge carriers can be continuously altered with increasing field, and hence some of their high-field properties may not necessarily reflect the presence of massless quasiparticles.The last decade has experienced considerable effort in the synthesis of materials with unconventional band structures, initiated by studies of graphene and topological insulators. Most recently, great interest is directed toward other exotic and topologically protected phases -Dirac and Weyl semimetals. In topological quantum semimetals linearly dispersing conduction and valence bands intersect at points or along lines in momentum space, and hence are supposed to allow the propagation of electron waves that behave as Dirac and Weyl fermions in the bulk. Many Dirac and Weyl semimetals show exceptional properties, such as an electrical conductivity higher than noble metals, high charge-carrier mobilities and extreme magnetoresistance (XMR) with field dependences varying between quasilinear [1-4] and near quadratic [5][6][7][8][9][10][11].