NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice

• Published in: Physiology & behavior 2014-05, Vol.130, p.91-98
• Main Authors: de Rezende, Vitor Bortolo, Rosa, Daniela Valadão, Comim, Clarissa Martinelli, Magno, Luiz Alexandre Viana, Rodrigues, Ana Lucia Severo, Vidigal, Paula, Jeromin, Andreas, Quevedo, João, Romano-Silva, Marco Aurélio
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Anti-Anxiety Agents - pharmacology; Antidepressive Agents, Tricyclic - pharmacology; Anxiety; Anxiety Disorders - drug therapy; Anxiety Disorders - physiopathology; Avoidance Learning - physiology; Behavior; Behavioral psychophysiology; Biological and medical sciences; Depression; Depressive Disorder - drug therapy; Depressive Disorder - physiopathology; Diazepam - pharmacology; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; Fundamental and applied biological sciences. Psychology; Imipramine - pharmacology; Knockout; Male; Medical sciences; Memory; Memory Disorders - physiopathology; Memory, Long-Term - physiology; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Miscellaneous; Mood disorders; NCS-1; Neuronal Calcium-Sensor Proteins - deficiency; Neuronal Calcium-Sensor Proteins - genetics; Neuronal Calcium-Sensor Proteins - physiology; Neuropeptides - deficiency; Neuropeptides - genetics; Neuropeptides - physiology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Recognition (Psychology) - physiology; Social Behavior
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2014.03.005

Abstract Sensing and regulating intracellular levels of calcium are essential for proper cellular function. In neurons, calcium sensing plays important roles in neuronal plasticity, neurotransmitter release, long-term synapse modification and ion channel activity. Neuronal calcium sensor-1 (NCS-1) is a member of the highly conserved neuronal calcium sensor family. Although NCS-1 has been associated with psychiatric conditions including autism, bipolar disorder and schizophrenia, it is unclear which role NCS-1 plays in behavior. To understand the involvement of NCS-1 in psychiatric conditions, we provided a comprehensive behavioral characterization of NCS-1 knockout (KO) mice. These mice grow and develop normally without apparent abnormalities in comparison to wild type littermates. However, open field showed that NCS-1 deficiency impairs novelty-induced exploratory activity in both KO and heterozygote (HT) mice. Moreover, NCS-1-deficiency also resulted in anxiety- and depressive-like behaviors as demonstrated by elevated plus maze, large open field, forced swim and tail suspension tasks. Furthermore, based on spontaneous object recognition test, non-aversive long-term memory was impaired in NCS-1 KO mice. In contrast, neither social behavior nor a kind of aversive memory was affected under NCS-1 deficiency. These data implicate NCS-1 in exploratory activity, memory and mood-related behaviors, suggesting that NCS-1 gene ablation may result in phenotypic abnormalities associated with neuropsychiatric disorders.