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

灵活使用信息并对不断变化的环境条件做出适当适应行为的能力对所有物种的生存都是必不可少的，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关键作用。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，包括在不同的行为策略和关于与不同风险和回报相关的不同选择的决策之间的转换。多巴胺在这些过程中的作用被认为部分是通过短暂的、“相”的中脑多巴胺神经元活动的增加和减少来调节的，这些神经元发出奖赏和非奖赏事件的信号。然而，阶段多巴胺活动在这些形式的行为灵活性中所起的具体作用不能用标准的药理学方法来确定。为了直接解决这个问题，目前的提议是要求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突发电刺激，或向该区域提供抑制输入，以模拟这些神经元在动物收到奖励或没有收到预期奖励时的行为方式。本质上，我们希望通过以一种特定的方式激活或抑制多巴胺神经元，我们可以模拟这些阶段事件，以确定它们对行为的控制，本质上欺骗大脑编码奖励或非奖励事件，导致行为变化。所需的设备对于我们采用这种方法是必不可少的，使我们能够提供第一个关于相多巴胺信号功能的直接实验数据。这些信息将提供至关重要的洞察力，以了解多巴胺交流的基本形式如何有助于与奖励相关的学习的不同方面，以及响应奖励偶发事件的变化而改变学习行为。

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.