T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants.
T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants.
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DOI：
10.3389/fnbeh.2014.00092
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发表时间：
2014
影响因子：
3
通讯作者：
Valjent E
中科院分区：
文献类型：
--
作者：
Gangarossa G;Laffray S;Bourinet E;Valjent E
神经元兴奋性的微调依赖于对钙离子稳态的严格控制。低电压激活的T型钙通道(Cav3.1、Cav3.2和CaV3.3亚型)在调节这些过程中起着关键作用。尽管它们广泛表达于中枢神经系统，但T型Cav3.2亚型在脑功能中的意义仍不清楚。在这里，我们研究了该亚型的基因消融在情感障碍中的作用，包括焦虑、认知功能以及对滥用药物的敏感性。通过广泛的行为分析，我们发现，cacna1h基因的遗传消融导致了焦虑样的表型，而新鲜感诱导的运动活动没有受到影响。T型通道Cav3.2的缺失也会引发海马体依赖的识别记忆受损。在T型Cav3.2缺陷小鼠中，由D-苯丙胺和可卡因引起的急性和敏感型多动运动显著减少。此外，给予T型阻滞剂TTA-A2可阻止在野生型小鼠中观察到的运动敏化的表达。综上所述，我们的数据显示，这种特殊的钙通道的生理活动是情感和认知行为所必需的。此外，我们的工作强调了T型通道阻滞剂作为逆转药物相关改变的治疗策略的兴趣。
The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type channel Cav3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca2+ channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations.
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影响因子：
3.7
作者：
Chen CC;Shen JW;Chung NC;Min MY;Cheng SJ;Liu IY
通讯作者：
Liu IY
影响因子：
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Brami-Cherrier, K;Valjent, E;Caboche, J
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Hammond, C
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通讯作者：
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