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

灵活地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，我们以前的工作表明大脑化学物质多巴胺在这些过程中起着至关重要的作用。某些药物对多巴胺信号传导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之间转换，以及对与不同风险和回报相关的不同选择做出决策。 多巴胺对这些过程的贡献被认为部分是由中脑多巴胺神经元活动的短暂的“阶段性”增加和减少介导的，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发挥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电刺激或向该区域提供抑制性输入，以模仿这些神经元在动物获得奖励或没有获得预期奖励时的行为方式。从本质上讲，我们希望通过以时间特异性的方式激活或抑制多巴胺神经元，我们可以模拟这些阶段性事件，以确定它们对行为的控制，本质上是欺骗大脑编码奖励或非奖励事件，从而导致行为的改变。所要求的设备是必不可少的，我们采用这种方法，使我们能够提供第一个直接的实验数据的功能相多巴胺信号。这些信息将提供至关重要的洞察力，了解多巴胺沟通的基本形式如何有助于奖励相关学习的不同方面，以及如何修改学习行为以应对奖励意外事件的变化。

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.