Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models

© 2020, The Author(s). Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS

A Simplified Gas Chromatographic Fatty-Acid Analysis by the Direct Saponification/Methylation Procedure and Its Application on Wild Tuna Larvae

A method for the direct preparation of fatty‐acid methyl esters (FAME) was simplified for fatty‐acid analysis of a single fish larva using gas chromatography (GC). The method included the isolation of a larval trunk and drying in a glass vial, followed by saponification of all the contents without prior lipid extraction. Thereafter, the fatty acids released were methylated by trimethylsilyldiazomethane. This method has advantages over another method, direct acid‐catalyzed transesterification, because both the saponification and methylation at room temperature can reduce loss of unsaturated fatty acids and formation of artifacts unavoidable in acidic reaction at high temperature. GC of the products showed that the simplified method can yield methyl esters without artifacts interfering analysis. More than 50 fatty acids were determined, which are twice as many as those previously analyzed using high‐performance liquid chromatography. Observation of consistent small impurities in GC of blank tests allowed the accurate determination of fatty acids by correcting the peak areas. Dry matter weights (<3 mg) and the total fatty‐acid contents displayed a linear relationship. Fatty‐acid analysis of wild larvae of bluefin tuna, yellowfin tuna, and skipjack tuna collected from the waters around Japan (n = 100) revealed that the eicosapentaenoic acid (EPA) level in bluefin tuna collected from the Japan Sea was significantly higher than that in the three species collected from Nansei Islands. The simplified direct saponification/methylation method will be a powerful tool for investigating growth and survival of individual larval tuna and other fish species

Individual variations in fatty acid composition and concentration as indicators of the nutritional condition of wild pointhead flounder larvae

We investigated the fatty acid compositions and concentrations of wild marine fish larvae with a highly accurate method because our knowledge of them has been seriously limited compared with cultured larvae. This study presents estimates of the fatty-acid-based nutritional condition of individual larvae in the field. Because the pointhead flounder Cleisthenes pinetorum displays relatively high stock size fluctuations, we investigated the developmental change in the fatty acid compositions of the body trunk, head, and eye and the annual fluctuations in the fatty acid concentrations in the trunk. We show that the process of fatty acid accumulation is not uniform across body parts and that the trunk is a better indicator of larval nutritional status than other parts because there is less time lag. Starved larvae with simultaneously high docosahexaenomic acid ratios and low total fatty acid concentrations, as observed in laboratory experiments, are rare in the wild. Thus, starved larvae must be removed rapidly by predators before they can experience a relatively long period of starvation in the wild. Fatty acid accumulation was greater in the larvae of the 2005 year class than in those of the 2006 year class in their first feeding stage, according to the optimal model derived with generalized linear model. A previous study indicated that the 2005 year class showed stronger recruitment than the 2006 year class. We conclude that the fatty acid analysis of wild larvae is a useful index of their nutritional status and mortality, especially in the first feeding stage

Contrast Sensitivity Function and Ocular Higher-Order Aberrations following Overnight Orthokeratology

PURPOSE. To evaluate relationships among contrast sensitivity function, ocular higher-order aberration, and myopic correction in eyes undergoing overnight orthokeratology for myopia. METHODS. A prospective study was conducted in 46 eyes of 23 patients undergoing orthokeratology. Inclusion criteria were spherical equivalent refraction between –1.00 and –4.00 diopters (D), refractive astigmatism up to 1.00 D, and best-corrected visual acuity of 20/20 or better. Ocular higher-order aberrations and contrast sensitivity function were determined before and 3 months after initiation of the procedure. We measured three indices of contrast sensitivity function: contrast sensitivity, low-contrast visual acuity, and letter contrast sensitivity with the CSV-1000 charts (Vector Vision Co., Greenville, OH). Area under the log contrast sensitivity function (AULCSF) was calculated from the contrast sensitivity data. RESULTS. Orthokeratology significantly improved logMAR uncorrected visual acuity (P � 0.0001; paired t-test) but significantly increased ocular higher-order aberrations (P � 0.0001) and decreased contrast sensitivity function, including AULCSF (P � 0.0001), low-contrast visual acuity (P � 0.0025), and letter contrast sensitivity (P � 0.0001; Wilcoxon signed-rank test). The induced changes in AULCSF, low-contrast visual acuity, and letter contrast sensitivity by orthokeratology showed significant correlation with changes in third-order (Pearson r � –0.430, P � 0.0026; r � 0.423, P � 0.0031; and Spearman rs � –0.351, P � 0.0186, respectively), fourth-orde

噴火湾とその周辺海域におけるソウハチ Cleisthenes pinetorum 仔魚の摂餌生態

The feeding habits of pointhead flounder Cleisthenes pinetorum larvae were investigated in and near Funka Bay, Hokkaido Island during 10-20 August 2001. As the larvae grew, the principal prey shifted from copepod nauplii (especially, Oithona similis and Pseudocalanus newmani) as the initial food item to copepodites and an appendicularia Oikopleura sp. Nauplii of Microsetella sp. were abundant in the sampling area, but few were eaten by the larvae. The number of prey in the larval digestive tracts increased from 08:55 and peaked near sunset, suggesting the larvae are visual day feeders. Nauplii concentrations in the water varied geographically, but the number of nauplii in the larval digestive tracts did not vary. Pointhead flounder larvae in the first feeding stage might not starve in and near Funka Bay in August 2001.2001年8月10-20日の期間，北海道噴火湾とその周辺海或においてソウハチCleisthenes pnietorum仔魚の摂自生態を調査した。仔魚は成長とともに，初期飼料であるかいあし類ノープリウス（特にOithona similisとPseudcalanus newmaniからコペポダイトや尾虫類Oikopleura属の1種へと主要餌生物を移行させていた。Microsetella属の1種のノープリウスは調査海域に豊富に生息していたが，仔魚にはほとんど摂餌されていなかった。仔魚1個体が摂餌していた餌生物の平均個体数は08:55から高くなり，日没前後に最も高い値を示したことから，仔魚は視覚捕食者であることが示された。水域によってノープリウスの密度は変動していたにもかかわらず，仔魚1個体が摂餌していたノープリウスの個体数は異ならなかった。2001年夏季の噴火湾とその周辺海域において，摂餌開始期のソウハチ仔魚の飢餓による死亡の可能性は低いと考えられた

Inheritance of growth ring components and the possibility of early selection for higher wood density in Japanese cedar (Cryptomeria japonica D. Don)

Abstract Key message We elucidated the age trends of narrow-sense heritability and phenotypic/genetic correlations and the age–age genetic correlation of growth ring components of Cryptomeria japonica D. Don by investigating progenies of controlled crossings by soft X-ray densitometry analysis. Wood density in the C. japonica breeding program can be efficiently improved by selecting trees with a higher earlywood density and latewood percentage as early as forest stand ages of 5–9 years. Context Wood density within the trunk is affected by the intra-ring wood density profile and its age trend from pith to bark. Wood density can be efficiently improved by clarifying whether wood density and highly correlated intra-ring components are under additive genetic control. Aims The aim of this study was to elucidate the age trends of narrow-sense heritability and phenotypic/genetic correlations of growth ring components and investigate the possibility of early selection for improving wood density in Cryptomeria japonica. Methods We quantified seven growth ring components (width, density, earlywood/latewood width, average earlywood/latewood density, and latewood percentage) for 5112 annual rings of 342 18-year-old trees derived from 24 controlled pollinated full-sib families of C. japonica plus tree clones by soft X-ray densitometry analysis. Genetic parameters and correlations among the seven growth ring components were analyzed using a linear mixed model and the breedR package. Results Earlywood density and latewood percentage exhibited a higher phenotypic and genetic correlation with ring density than the other ring components at almost all ages. Earlywood density and latewood percentage exhibited a lower correlation with ring width than the other ring components after a stand age of 5 years. The age–age genetic correlation of earlywood density and latewood percentage was 0.70 for a stand age of 17 years and was strong at stand ages of 5 and 9 years. Conclusion Efforts focusing on improving earlywood density and latewood percentage may contribute to improving wood density efficiently in tree breeding programs for C. japonica. Traits related to the ring density of C. japonica trees can possibly be selected as early as stand ages of 5–9 years, and the required period for progeny selection may be substantially shortened when selecting trees with high wood density