Genetic mutations in the gene encoding transport protein particle complex 9 (trappc9), a subunit of TRAPP that acts as a guanine nucleotide exchange factor for rab proteins, cause intellectual disability with brain structural malformations by elusive mechanisms. Here, we report that trappc9-deficient mice exhibit a broad range of behavioral deficits and postnatal delay in growth of the brain. Contrary to volume decline of various brain structures, the striatum of trappc9 null mice was enlarged. An imbalance existed between dopamine D1 and D2 receptor containing neurons in the brain of trappc9-deficient mice; pharmacological manipulation of dopamine receptors improved performances of trappc9 null mice to levels of wild-type mice on cognitive tasks. Loss of trappc9 compromised the activation of rab11 in the brain and resulted in retardation of endocytic receptor recycling in neurons. Our study elicits a pathogenic mechanism and a potential treatment for trappc9-linked disorders including intellectual disability.

The D2 dopamine receptor (Drd2) is implicated in several brain disorders such as schizophrenia, Parkinson’s disease, and drug addiction. Drd2 is also the primary target of both antipsychotics and Parkinson’s disease medications. Although the expression pattern of Drd2 is relatively well known in mouse brain, the temporal and spatial distribution of Drd2 is lesser clear in rat brain due to the lack of Drd2 reporter rat lines. Here, we used CRISPR/Cas9 techniques to generate two knockin rat lines: Drd2::Cre and Rosa26::loxp-stop-loxp-tdTomato. By crossing these two lines, we produced Drd2 reporter rats expressing the fluorescence protein tdTomato under the control of the endogenous Drd2 promoter. Using fluorescence imaging and unbiased stereology, we revealed the cellular expression pattern of Drd2 in adult and postnatal rat forebrain. Strikingly, the Drd2 expression pattern differs between Drd2 reporter rats and Drd2 reporter mice generated by BAC transgene in prefrontal cortex and hippocampus. These results provide fundamental information needed for the study of Drd2 function in rat forebrain. The Drd2::Cre rats generated here may represent a useful tool to study the function of neuronal populations expressing Drd2.

Blended instruction integrating off-line and on-line teaching has become an important instrument for promoting educational reform and innovation. However, the results of current empirical studies diverge on the effect of blended instruction on student performance, which necessitates further research on the effectiveness of blended instruction and related factors. This study, using an evidence-based meta-analytical approach, conducts a quantitative analysis of 106 experimental and quasi- experimental studies published from January 2000 to September 2021 in China and abroad, and systematically examines the effectiveness of blended instruction. The research finds that: i) The summary effect size (ES) of the included sample is 0.669 (n=142), indicating that blended instruction has above-moderate positive effects on student performance, especially on student learning motivation and academic emotions and attitude; ii) In terms of education levels, experimental periods and class sizes, blended instruction has the most significant positive effect on junior and senior secondary school students, on a teaching period from one to three months, and on a class size of 51 to 100 students; iii) Regarding the proportion and interactive patterns of online teaching, 50% composition of online teaching and synchronous or synchronous + asynchronous interaction exert the most significant positive effects on student learning. iv) Teaching methods including task-driven learning, role-playing, inquiry-based teaching, and case-based teaching have greater positive effects on student performance than other methods. Group study yields a greater effect on promoting student learning compared to individual study. Based on the findings, the present study also makes suggestions for the effective practice of blended instruction.

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