title: Netrin-G1 regulates fear-like and anxiety-like behaviors in dissociable neural circuits.
abstract: In vertebrate mammals, distributed neural circuits in the brain are involved in emotion-related behavior. Netrin-G1 is a glycosyl-phosphatidylinositol-anchored synaptic adhesion molecule whose deficiency results in impaired fear-like and anxiety-like behaviors under specific circumstances. To understand the cell type and circuit specificity of these responses, we generated netrin-G1 conditional knockout mice with loss of expression in cortical excitatory neurons, inhibitory neurons, or thalamic neurons. Genetic deletion of netrin-G1 in cortical excitatory neurons resulted in altered anxiety-like behavior, but intact fear-like behavior, whereas loss of netrin-G1 in inhibitory neurons resulted in attenuated fear-like behavior, but intact anxiety-like behavior. These data indicate a remarkable double dissociation of fear-like and anxiety-like behaviors involving netrin-G1 in excitatory and inhibitory neurons, respectively. Our findings support a crucial role for netrin-G1 in dissociable neural circuits for the modulation of emotion-related behaviors, and provide genetic models for investigating the mechanisms underlying the dissociation. The results also suggest the involvement of glycosyl-phosphatidylinositol-anchored synaptic adhesion molecules in the development and pathogenesis of emotion-related behavior.
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Sano
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Masuda
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ando
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005239:Fear; D051379:Mice; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology; D000075385:Netrins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D000075385:Netrins; C000618035:Ntng1 protein, mouse