Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice
Calcium (Ca2+) influx through voltage-gated Ca2+ channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca2+ signaling, such as the CACNA1C, CACNB2, and CACNA1I...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-06-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00141/full |
| _version_ | 1811301577508519936 |
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| author | Akito eNakao Takafumi eMiki Hirotaka eShoji Miyuki eNishi Hiroshi eTakeshima Tsuyoshi eMiyakawa Yasuo eMori |
| author_facet | Akito eNakao Takafumi eMiki Hirotaka eShoji Miyuki eNishi Hiroshi eTakeshima Tsuyoshi eMiyakawa Yasuo eMori |
| author_sort | Akito eNakao |
| collection | DOAJ |
| description | Calcium (Ca2+) influx through voltage-gated Ca2+ channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca2+ signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC β subunits. To examine the role of the BARP in higher brain functions, we generated BARP knockout (KO) mice and conducted a comprehensive battery of behavioral tests. BARP KO mice exhibited greatly reduced locomotor activity, as evidenced by decreased vertical activity, stereotypic counts in the open field test, and activity level in the home cage, and longer latency to complete a session in spontaneous T-maze alteration test, which reached study-wide significance. Acoustic startle response was also reduced in the mutants. Interestingly, they showed multiple behavioral phenotypes that are seemingly opposite to those seen in the mouse models of schizophrenia and its related disorders, including increased working memory, flexibility, prepulse inhibition, and social interaction, and decreased locomotor activity, though many of these phenotypes are statistically weak and require further replications. These results demonstrate that BARP is involved in the regulation of locomotor activity and, possibly, emotionality. The possibility was also suggested that BARP KO mice may serve as a unique tool for investigating the pathogenesis/pathophysiology of schizophrenia and related disorders. Further evaluation of the molecular and physiological phenotypes of the mutant mice would provide new insights into the role of BARP in higher brain functions. |
| first_indexed | 2024-04-13T07:11:12Z |
| format | Article |
| id | doaj.art-5eff047a613b46e680575201163c2544 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-13T07:11:12Z |
| publishDate | 2015-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-5eff047a613b46e680575201163c25442022-12-22T02:56:52ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532015-06-01910.3389/fnbeh.2015.00141136527Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout miceAkito eNakao0Takafumi eMiki1Hirotaka eShoji2Miyuki eNishi3Hiroshi eTakeshima4Tsuyoshi eMiyakawa5Yasuo eMori6Fujita Health UniversityKyoto UniversityFujita Health UniversityKyoto UniversityKyoto UniversityFujita Health UniversityKyoto UniversityCalcium (Ca2+) influx through voltage-gated Ca2+ channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca2+ signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC β subunits. To examine the role of the BARP in higher brain functions, we generated BARP knockout (KO) mice and conducted a comprehensive battery of behavioral tests. BARP KO mice exhibited greatly reduced locomotor activity, as evidenced by decreased vertical activity, stereotypic counts in the open field test, and activity level in the home cage, and longer latency to complete a session in spontaneous T-maze alteration test, which reached study-wide significance. Acoustic startle response was also reduced in the mutants. Interestingly, they showed multiple behavioral phenotypes that are seemingly opposite to those seen in the mouse models of schizophrenia and its related disorders, including increased working memory, flexibility, prepulse inhibition, and social interaction, and decreased locomotor activity, though many of these phenotypes are statistically weak and require further replications. These results demonstrate that BARP is involved in the regulation of locomotor activity and, possibly, emotionality. The possibility was also suggested that BARP KO mice may serve as a unique tool for investigating the pathogenesis/pathophysiology of schizophrenia and related disorders. Further evaluation of the molecular and physiological phenotypes of the mutant mice would provide new insights into the role of BARP in higher brain functions.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00141/fullBehaviorpsychiatric disordersknockout mousevoltage-gated calcium channelsvoltage-gated calcium channel beta-anchoring and -regulatory protein |
| spellingShingle | Akito eNakao Takafumi eMiki Hirotaka eShoji Miyuki eNishi Hiroshi eTakeshima Tsuyoshi eMiyakawa Yasuo eMori Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice Frontiers in Behavioral Neuroscience Behavior psychiatric disorders knockout mouse voltage-gated calcium channels voltage-gated calcium channel beta-anchoring and -regulatory protein |
| title | Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice |
| title_full | Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice |
| title_fullStr | Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice |
| title_full_unstemmed | Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice |
| title_short | Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice |
| title_sort | comprehensive behavioral analysis of voltage gated calcium channel beta anchoring and regulatory protein knockout mice |
| topic | Behavior psychiatric disorders knockout mouse voltage-gated calcium channels voltage-gated calcium channel beta-anchoring and -regulatory protein |
| url | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00141/full |
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