Achievements 

https://doi.org/10.3389/fncel.2024.1513347

Autism spectrum disorder (ASD) is characterized by social deficits and restricted behaviors, with developmental defects in GABAergic circuits proposed as a key underlying etiology. Here, we introduce the V-Y assay, a novel space preference test in which one arm of the Y-maze is initially hidden and later revealed as a novel space. Using an ASD mouse model with FOXG1 haploinsufficiency, which exhibits ASD-like social impairments that can be either exacerbated or ameliorated by GABAergic circuit manipulations, we observed impaired novel space preference and exploratory behavior in the V-Y assay. Interestingly, unlike social phenotypes, novel space preference was initially established by three weeks of age but regressed by six weeks. Furthermore, alterations in GABAergic signaling via Gad2 mutation did not affect novel space preference, in contrast to their impact on social behaviors. These findings reveal that the regression of novel space preference in ASD follows a distinct developmental trajectory from GABA-driven social impairments, providing new insights into the mechanisms underlying ASD.

https://doi.org/10.1016/j.neures.2024.08.002

Environmental factors have well-documented impacts on brain development and mental health. Therefore, it is crucial to employ a reliable assay system to assess the spatial preference of model animals. In this study, we introduced an unbiased quadrant chamber assay system and discovered that parental pup-gathering behavior takes place in a very efficient manner. Furthermore, we found that test mice exhibited preferences for specific environments in both spontaneous and parental pup-gathering behavior contexts. Notably, the spatial preferences of autism spectrum disorder model animals were initially suppressed but later equalized during the spontaneous behavior assay, accompanied by increased time spent in the preferred chamber. In conclusion, our novel quadrant chamber assay system provides an ideal platform for investigating the spatial preference of mice, offering potential applications in studying environmental impacts and exploring neurodevelopmental and psychiatric disorder models.

https://doi.org/10.1073/pnas.2317783121

GABAergic inhibitory interneurons, originating from the embryonic ventral forebrain territories, traverse a convoluted migratory path to reach the neocortex. These interneuron precursors undergo sequential phases of tangential and radial migration before settling into specific laminae during differentiation. Here, we show that the developmental trajectory of FoxG1 expression is dynamically controlled in these interneuron precursors at critical junctures of migration. By utilizing mouse genetic strategies, we elucidate the pivotal role of precise changes in FoxG1 expression levels during interneuron specification and migration. Our findings underscore the gene dosage–dependent function of FoxG1, aligning with clinical observations of FOXG1 haploinsufficiency and duplication in syndromic forms of autism spectrum disorders. In conclusion, our results reveal the finely tuned developmental clock governing cortical interneuron development, driven by temporal dynamics and the dose-dependent actions of FoxG1.

https://www.nature.com/articles/s41467-021-23987-z

Abnormalities in GABAergic inhibitory circuits have been implicated in the etiology of autism spectrum disorder (ASD), but when and how GABAergic dysfunction leads to ASD-related social impairments is poorly understood. Here we have selectively manipulated the expression of the syndromic ASD gene FOXG1 in rodent models to identify that the second postnatal week is the critical period to establish juvenile inhibitory circuits and to prevent ASD social phenotypes. Either increased or decreased FoxG1 levels result in social impairments but only when alterations take place in both excitatory and inhibitory populations, indicating a pre-and postsynaptic role for FoxG1 in GABAergic circuit development. We find that supplementation of GABAergic interneuron precursors prior to the critical period ameliorates ASD-related circuit and behavioral phenotypes, whereas reduction in GABAergic tone via Gad2 mutation exacerbates social impairments. Our results reveal the developmental timing and inhibitory circuit mechanisms that are promising for therapeutic intervention in ASD.

https://bsd.neuroinf.jp/wiki/大脳皮質介在ニューロンの発生

https://www.sciencedirect.com/science/article/pii/S0168010218305248?via%3Dihub

https://www.jneurosci.org/content/35/37/12869

https://link.springer.com/chapter/10.1007/978-4-431-54496-8_5

https://www.sciencedirect.com/science/article/pii/S0896627312004229?via%3Dihub

Campbell K and Waclaw R: F1000Prime Recommendation of Evaluation In F1000Prime, 23 Jul 2012; 

F1000Prime.com/717948664#eval793453766

Mueller U and Franco S: F1000Prime Recommendation of Evaluation In F1000Prime, 25 Oct 2012; 

F1000Prime.com/717948664#eval793463266

https://academic.oup.com/cercor/article/21/4/845/287805

https://www.jneurosci.org/content/30/5/1582.long

https://www.jneurosci.org/content/27/29/7786.long

https://www.sciencedirect.com/science/article/pii/S0959438806001188?via%3Dihub

https://www.jneurosci.org/content/24/14/3672.long