Imaging neurochemical and neural signalling with fiber photometry

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都是至关重要的，我们以前的工作已经表明大脑化学物质多巴胺，特别是在额叶中，在这些过程中起着至关重要的作用。不同大脑区域（包括额叶及其皮层下连接）内多巴胺信号的中断会阻碍不同形式的认知灵活性和其他形式的认知，包括在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，并且可能与接收这些多巴胺信号的神经元活动的类似变化有关。然而，不同的行为事件是如何通过额叶和相互连接的区域内的神经化学和神经活动的短暂变化来编码的，以及它们对行为的因果贡献仍然有待澄清。 为了直接解决这个问题，目前的提案要求专门的纤维光度成像设备，使我们能够监测多巴胺传输和神经活动的变化。还需要额外的设备，使我们能够同时操纵这些信号在时间上精确的方式与激光。本质上，我们希望通过监测正常条件下以及在特定行为事件（例如，行动的发起，对其结果的评估），我们将精确地确定这些信号如何在秒到秒的基础上控制行为。所要求的设备是必不可少的，我们采用这种方法，使我们能够提供直接的实验数据的功能相神经化学和神经信号。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, particularly within the frontal lobes plays a crucial role in these processes. Disruptions in dopamine signaling within different brain regions including the frontal lobes and its subcortical connections impedes different forms of cognitive flexibility and other forms of cognition, 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, and may be associated with similar changes in activity in neurons that receive these dopamine signals. However, how different behavioural events are encoded by brief changes in neurochemical and neural activity within the frontal lobes and interconnected regions remains to be clarified, as does their causal contribution to behavior. To address this issue directly, the present proposal is requesting specialized fiber photometry imagining equipment that will enable us to monitor changes in dopamine transmission and neural activity. Additional equipment is also requested to enable us to concurrently manipulate these signals in a temporally-precise manner with laser light. In essence, we hope that by monitoring changes in this activity under normal conditions and when activating/inhibiting dopamine neurons during specific behavioral events (e.g., initiation of actions, evaluation of their outcomes) we will ascertain precisely how these signals control behaviour on a second-to-second basis. The requested equipment is essential for us to employ this approach, enabling us to provide direct experimental data regarding the function of phasic neurochemical and neural 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.