Spatial Learning and Motor Deficits in Vacuolar Protein Sorting-associated Protein 13b (Vps13b) Mutant Mouse

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.

Imaging and analysis of genetically encoded calcium indicators linking neural circuits and behaviors

Confirming the direct link between neural circuit activity and animal behavior has been a principal aim of neuroscience. The genetically encoded calcium indicator (GECI), which binds to calcium ions and emits fluorescence visualizing intracellular calcium concentration, enables detection of in vivo neuronal firing activity. Various GECIs have been developed and can be chosen for diverse purposes. These GECI-based signals can be acquired by several tools including two-photon microscopy and microendoscopy for precise or wide imaging at cellular to synaptic levels. In addition, the images from GECI signals can be analyzed with open source codes including constrained non-negative matrix factorization for endoscopy data (CNMF_E) and miniscope 1-photon-based calcium imaging signal extraction pipeline (MIN1PIPE), and considering parameters of the imaged brain regions (e.g., diameter or shape of soma or the resolution of recorded images), the real-time activity of each cell can be acquired and linked with animal behaviors. As a result, GECI signal analysis can be a powerful tool for revealing the functions of neuronal circuits related to specific behaviors.

Effects of the Female Estrous Cycle on the Sexual Behaviors and Ultrasonic Vocalizations of Male C57BL/6 and Autistic BTBR T+ tf/J Mice

A primary characteristic of autism, which is a neurodevelopmental disorder, is impaired social interaction and communication. Furthermore, patients with autism frequently show abnormal social recognition. In mouse models of autism, social recognition is usually assessed by examining same-sex social behavior using various tests, such as the three-chamber test. However, no studies have examined the ability of male mice with autism to recognize the estrous cycle of female partners. In this study, we investigated the sexual behaviors, especially mounting and ultrasonic vocal communication (USV), of BTBR T+ tf/J (BTBR) mice, which are used as a well-known mouse model of autism, when they encountered estrus or diestrus female mice. As expected, C57BL/6 mice mounted more female mice in the estrus stage compared with the diestrus stage. We found that BTBR mice also mounted more female mice in the estrus stage than female mice in the diestrus stage. Although the USV emission of male mice was not different between estrus and diestrus female mice in both strains, the mounting result implies that BTBR mice distinguish sexual receptivity of females.