Contribution of L-type Ca2+ channel subtypes to burst firing of dopaminergic cells in the mouse ventral tegmental area

L 型 Ca2 通道亚型对小鼠腹侧被盖区多巴胺能细胞爆发放电的贡献

• 批准号: 261384-2008
• 负责人: Chen, Xihua
• 金额: $ 4.17万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=547739
• 关键词: Contribution; type; Ca2+; channel; subtypes

Increased dopamine in the brain is believed to contribute to addiction and psychosis, it is therefore important to understand how dopamine output is regulated. Cells that make and release dopamine fire in different temporal patterns, clustered firing in short bursts has been found to be more effective in raising dopamine levels. We have previously reported that the L-type calcium channel is involved in generating this particular firing pattern, now we propose to examine this in more detail using mice that do not have one subtype of the ion channel. The ion channel in question is important for many functions, it is expected that a given subtype may be more implicated in a particular functions involving a specific group of cells in the brain. We will first examine which subtype is important for encoding burst firing to release more dopamine. We further reason that different dopamine cells may have different subtypes of the L-type ion channel that are connected to different parts of the brain. These subtypes will then be involved in regulating dopamine output to different parts of the brain depending on their connectivity. The proposed experiments in this program of research will provide necessary details for us to understand the workings of the brain dopamine system and will also provide clues as to how to target the system in the management of addiction and psychosis.

大脑中增加的多巴胺被认为会导致成瘾和精神病，因此了解多巴胺的输出是如何调节的是很重要的。以不同的时间模式产生和释放多巴胺的细胞，短时间的群集性放电被发现在提高多巴胺水平方面更有效。我们以前已经报道过L类型的钙通道参与了这种特殊的放电模式的产生，现在我们建议使用没有离子通道的一个亚型的小鼠来更详细地研究这一点。所讨论的离子通道对许多功能都很重要，预计给定的亚型可能与涉及大脑中特定细胞组的特定功能更相关。我们将首先研究哪种亚型对编码猝发放电以释放更多多巴胺是重要的。我们进一步推测，不同的多巴胺细胞可能有不同亚型的L类型的离子通道，连接到大脑的不同部分。然后，这些亚型将参与调节多巴胺输出到大脑不同部位，这取决于它们的连通性。这项研究计划中提议的实验将为我们了解大脑多巴胺系统的工作原理提供必要的细节，并将为如何在成瘾和精神病管理中针对该系统提供线索。