Simultaneous analysis of social behaviors and neural responses in mice using round social arena system

Kim, Sunwhi; Kim, Yong-Eun; Kim, Il Hwan

doi:10.1016/j.xpro.2022.101722

Cited by 4 publications

(6 citation statements)

References 8 publications

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“…The behavior was recorded using a camera mounted overhead. The test animals’ interaction with strangers was determined by the reciprocal sniffing time as described previously (125, 126). The test animals’ interaction with a novel object was determined by the sniffing time that was defined as each instance in which a test mouse’s nose was oriented in a 10-degree head orientation and comes within 2 cm toward a mouse or a wire cup as described previously (14).…”

Section: Methodsmentioning

confidence: 99%

The autism-associated loss of δ-catenin functions disrupts social behaviors

Mendez-Vazquez¹,

Roach²,

Nip³

et al. 2023

Preprint

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δ–catenin is expressed in excitatory synapses and functions as an anchor for the glutamatergic AMPA receptor (AMPAR) GluA2 subunit in the postsynaptic density. The glycine 34 to serine (G34S) mutation in theδ–cateningene is found in autism spectrum disorder (ASD) patients and induces loss of δ–catenin functions at excitatory synapses, which is presumed to underlie ASD pathogenesis in humans. However, how the G34S mutation causes loss of δ–catenin functions to induce ASD remains unclear. Here, using neuroblastoma cells, we discover that the G34S mutation generates an additional phosphorylation site for glycogen synthase kinase 3β (GSK3β). This promotes δ–catenin degradation and causes the reduction of δ–catenin levels, which likely contributes to the loss of δ–catenin functions. Synaptic δ–catenin and GluA2 levels in the cortex are significantly decreased in mice harboring the δ–catenin G34S mutation. The G34S mutation increases glutamatergic activity in cortical excitatory neurons while it is decreased in inhibitory interneurons, indicating changes in cellular excitation and inhibition. δ–catenin G34S mutant mice also exhibit social dysfunction, a common feature of ASD. Most importantly, inhibition of GSK3β activity reverses the G34S-induced loss of δ–catenin function effects in cells and mice. Finally, using δ–catenin knockout mice, we confirm that δ–catenin is required for GSK3β inhibition-induced restoration of normal social behaviors in δ–catenin G34S mutant animals. Taken together, we reveal that the loss of δ–catenin functions arising from the ASD-associated G34S mutation induces social dysfunction via alterations in glutamatergic activity and that GSK3β inhibition can reverse δ–catenin G34S-induced synaptic and behavioral deficits.

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Section: Methodsmentioning

confidence: 99%

The autism-associated loss of δ-catenin functions disrupts social behaviors

Mendez-Vazquez¹,

Roach²,

Nip³

et al. 2023

Preprint

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“…Round Social Arena (RSA) test: Expanding on our previous studies, the RSA test was specifically designed to emphasize social interactions while minimizing the distractors and spatial biases often encountered in traditional 3-chamber tests 37,44 . The RSA consists of a circular arena (diameter: 49 cm) equipped with a central 3D-printed transparent bar cage (diameter: 8 cm, height: 10.5 cm) designed to house a social stimulus mouse.…”

Section: Behavioral Experimentsmentioning

confidence: 99%

Monosynaptically-interconnected Network Module (MNM) Approach for High-Resolution Brain Sub-Network Analysis

Kim,

Ujihara

et al. 2024

Preprint

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We introduce the Monosynaptically-interconnected Network Module (MNM) approach, an innovative method designed for efficiently analyzing the anatomical structure and functional dynamics of specific brain network modulesin vivo. Utilizing an Intein-mediated split-Cre system combined with bidirectional adeno-associated viruses, this technique precisely targets and manipulates monosynaptically interconnected modular subnetworks in freely moving animals. We demonstrate its utility through anatomical and functional mapping of a specific MNM encompassing the prefrontal cortex (PFC), basolateral amygdala (BLA), and intermediary hub regions. Specifically, the MNM approach with Cre-reporter mice visualizes detailed network architecture and enables the tracing of axonal connections among the nodes in the network. Furthermore, integration of the MNM approach with Cre-dependent Ca2+indicator and multi-fiber photometry in freely moving mice reveals enhanced correlative network activities in social contexts. This versatile technique offers significant potential for advancing our understanding of network functions that underlie complex behaviors, providing a modular network perspective.

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“…Round social arena (RSA) test: RSA paradigm was developed in our previous study for precise analysis of social behaviors 24,30 . This test was performed in a round-shaped chamber (49 (D) X 45 (H) cm) under 35 lx illumination.…”

Section: Behavioral Testsmentioning

confidence: 99%

“…Next, we investigated social and repetitive behaviors, the core behavioral domains commonly affected by ASD 29 . To precisely monitor detailed social behaviors, we used a Round Social Arena (RSA) paradigm as described in our previous studies 24,30 (Fig. 2i).…”

Section: Introductionmentioning

confidence: 99%

“…Leica VT1200S vibratome. The slices were placed in oxygenated NMDG-aCSF at30-32 °C for 12 min, then allowed to recover at RT in oxygenated HEPES-aCSF containing 92 mM NaCl, 2.5 mM KCl, 1.25 mM NaH 2 PO 4 , 30 mM NaHCO 3 , 20 mM HEPES, 25 mM D-glucose, 2 mM thiourea, 5 mM sodium ascorbate, 3 mM sodium pyruvate, 2 mM CaCl 2 , and 2 mM MgSO 4 with pH 7.4 and osmolarity ~315 mOsm for a minimum of 50 minutes. During the recording, slices were maintained in oxygenated external bath solution containing 119 mM NaCl, 2.5 mM KCl, 1.25 mM NaH 2 PO 4 , 24 mM NaHCO 3 , 12.5 mM D-…”

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confidence: 99%

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Endothelial SHANK3 Controls Tight Junction of Neonatal Blood-Brain Barrier

Kim,

Kim

et al. 2024

Preprint

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Autism spectrum disorder (ASD) is a neurodevelopmental disability condition arising from the combination of genetic and environmental factors. Despite the blood-brain barrier (BBB) serving as a crucial gatekeeper, conveying environmental influences into the brain parenchyma, the contributions of BBB in ASD pathogenesis remain largely uncharted. Here we report that a novel form of SHANK3, a gene strongly associated with Phelan-McDermid syndrome and ASD2, expresses in the BBB-forming brain endothelial cells (BECs) and regulates tight junctional (TJ) integrity essential for maintaining the BBB’s barrier function. Loss of Shank3 disrupts the TJ of BECs, leading to increased paracellular passage through endothelial linings. Neonates with endothelium-specific SHANK3 knockout exhibit increased BBB permeability, reduced neuronal excitability, and impaired ultra-sonic communications. Surprisingly, while BBB permeability is restored during adult age, the mutant mice continue to display reduced neuronal excitability, impaired sociability, and repetitive responses. Further investigation reveals that the hyperpermeability resulting from TJ disruption is attributed to the β-Catenin imbalance triggered by SHANK3 knockout, which is rescued by normalizing β-Catenin signaling in vitro and in vivo. These findings highlight a previously unknown pathogenic mechanism stemming from the ASD-risk SHANK3, emphasizing the significance of neonatal BECs in the BBB as a potential therapeutic target of ASD

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Simultaneous analysis of social behaviors and neural responses in mice using round social arena system

Cited by 4 publications

References 8 publications

The autism-associated loss of δ-catenin functions disrupts social behaviors

The autism-associated loss of δ-catenin functions disrupts social behaviors

Monosynaptically-interconnected Network Module (MNM) Approach for High-Resolution Brain Sub-Network Analysis

Endothelial SHANK3 Controls Tight Junction of Neonatal Blood-Brain Barrier

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