Comprehensive Behavioral Phenotyping of Ryanodine Receptor type 3 (RyR3) Knockout Mice: Decreased Social Contact Duration in Two Social Interaction Tests

Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University Toyoake, Japan.
Frontiers in Behavioral Neuroscience (Impact Factor: 3.27). 02/2009; 3:3. DOI: 10.3389/neuro.08.003.2009
Source: PubMed


Dynamic regulation of the intracellular Ca2+ concentration is crucial for various neuronal functions such as synaptic transmission and plasticity, and gene expression. Ryanodine receptors (RyRs) are a family of intracellular calcium release channels that mediate calcium-induced calcium release from the endoplasmic reticulum. Among the three RyR isoforms, RyR3 is preferentially expressed in the brain especially in the hippocampus and striatum. To investigate the behavioral effects of RyR3 deficiency, we subjected RyR3 knockout (RyR3-/-) mice to a battery of behavioral tests. RyR3-/- mice exhibited significantly decreased social contact duration in two different social interaction tests, where two mice can freely move and make contacts with each other. They also exhibited hyperactivity and mildly impaired prepulse inhibition and latent inhibition while they did not show significant abnormalities in motor function and working and reference memory tests. These results indicate that RyR3 has an important role in locomotor activity and social behavior.

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    • "In agreement with the role of RyR in synaptic plasticity, it was reported that RyR may play a role in learning and memory. Thus, RyR3 knockout mice exhibit decreased social behavior [171], and memory retention is accompanied by increased expression of RyR2 mRNA in the hippocampus of water maze-trained rats as compared to swimming controls [172]. "
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    • "Tendency to spend time with a novel mouse versus a novel nonsocial object is evaluated in a social approach apparatus (Figure 1). This 3-chambered assay, which was developed by our team to provide a simple measure of general sociability,30 is widely used as an initial, highthroughput test for social deficits in mouse models of autism.27,32,34,38,41,64-70 "
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    • "Spatial learning is tightly correlated with selective upregulation of RyR expression (Adasme et al. 2011; Cavallaro et al. 1997; Yang et al. 2009; Zhao et al. 2000). Targeted deletion of RyR3 in mice causes impairments in social behavior (Matsuo et al. 2009) and deficits in contextual fear conditioning but improves spatial learning in the Morris water maze task (Futatsugi et al. 1999; Kouzu et al. 2000), whereas selective knockdown of RyR2 and RyR3 impairs avoidance memory processes (Galeotti et al. 2008). Previous studies have implicated a local release of Ca 2+ from intracellular stores in the maintenance of dendrites (Lohmann et al. 2002), the regulation of the motility of dendritic filopodia (Lohmann et al. 2005), and the increased size of dendritic spines (Korkotian and Segal 1999). "
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