Behavioural testing equipment for investigating the role of phasic dopamine signaling in cognitive flexibility

用于研究阶段性多巴胺信号传导在认知灵活性中的作用的行为测试设备

• 批准号: 390160-2010
• 负责人: Floresco, Stanley
• 金额: $ 2.05万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments - Category 1 (<$150,000)
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=443122
• 关键词: Behavioural; testing; equipment; investigating; role

The ability to use information flexibly and execute appropriate adaptive behaviours in response to changing environmental conditions is essential for survival in all species, and our previous work has shown the brain chemical dopamine plays a crucial role in these processes. Disruptions in dopamine signaling with certain drugs impedes different forms of cognitive flexibility, including shifting between different behavioural strategies and decision making about different choices associated with different risks and rewards. The contribution of dopamine to these processes is thought to be mediated in part by brief, "phasic" increases and decreases in the activity of midbrain dopamine neurons that signal rewarded and non-rewarded events. However, the specific role that phasic dopamine activity plays in these forms of behavioural flexibility cannot be ascertained with standard pharmacological approaches. To address this issue directly, the present proposal is requesting specialized behavioural testing equipment that will enable us to deliver discrete bursts of electrical stimulation to dopamine neurons or inhibitory inputs to this region, to mimic the way these neurons behave when animals receive reward, or do not receive an expected reward. In essence, we hope that by activating or inhibiting dopamine neurons in a temporally specific manner we can mimic these phasic events to ascertain their control over behaviour, essentially tricking the brain into encoding a rewarded or non-rewarded events, leading to alterations in behaviour. The requested equipment is essential for us to employ this approach, enabling us to provide the first direct experimental data regarding the function of phasic dopamine signaling. This information will provide crucial insight into how a fundamental form of dopamine communication contributes to different aspects of reward-related learning and modification of learned behaviours in response to changes in reward contingencies.

灵活使用信息并执行适当的适应行为以应对不断变化的环境条件的能力对于所有物种的生存至关重要，我们之前的工作表明，大脑化学物质多巴胺在这些过程中发挥着至关重要的作用。某些药物对多巴胺信号的干扰会阻碍不同形式的认知灵活性，包括不同行为策略之间的转换以及与不同风险和回报相关的不同选择的决策。 多巴胺对这些过程的贡献被认为部分是通过中脑多巴胺神经元活性的短暂、“阶段性”增加和减少来介导的，这些神经元发出奖励和非奖励事件的信号。然而，阶段性多巴胺活性在这些形式的行为灵活性中所起的具体作用无法通过标准药理学方法来确定。为了直接解决这个问题，本提案要求使用专门的行为测试设备，使我们能够向多巴胺神经元提供离散的电刺激或向该区域提供抑制性输入，以模拟这些神经元在动物收到奖励或未收到预期奖励时的行为方式。本质上，我们希望通过以时间特定的方式激活或抑制多巴胺神经元，我们可以模仿这些阶段性事件，以确定它们对行为的控制，从本质上欺骗大脑编码奖励或非奖励事件，从而导致行为的改变。所需的设备对于我们采用这种方法至关重要，使我们能够提供有关相位多巴胺信号传导功能的第一个直接实验数据。这些信息将为我们提供重要的见解，让我们了解多巴胺交流的基本形式如何促进与奖励相关的学习的不同方面，以及如何根据奖励意外事件的变化来修改习得的行为。