Bussey-Saksida touch screen chambers for monitoring cognitive behaviour in mice

相当多的加拿大人患有肥胖症，在控制食物摄入量方面存在困难。控制食物摄入量的困难源于消费食物的动机增加和抑制食物摄取的能力减弱。我的实验室主要关注腹侧被盖区(VTA)的多巴胺神经元，它编码了对线索的学习，这些线索预测了奖励和增加了获得食物的动机，这些线索是由它们在目标结构(如纹状体)中的输出驱动的。该研究计划的首要目标是描绘动机状态和决策过程中潜在的神经回路，并确定这些回路节点中与食物摄入量增加相关的神经适应。VTA多巴胺能神经元的谷氨酸能输入调节与食物有关的线索的学习。此外，皮层内的回路及其向纹状体的投射可能牵涉到是否进食的决定。利用药理学和膜片钳电生理学的结合，我们在确定这些回路节点内的突触强度如何随激素或神经肽发出的饱腹感状态而变化方面取得了重大进展。我们现在处于该项目的关键阶段，我们需要了解这些机制在病理生理环境中是如何工作的。事实上，对食物的异常动机导致食物摄入量增加，可能会导致认知行为的改变，包括决策和冲动。这项提议是为了让基金购买一种触摸屏系统来测量小鼠的认知行为，这样结合光遗传学，我们就可以分离出不同电路对预测奖励、决策和冲动的线索学习的贡献。在用Bussey-Saksida小室进行行为评估后，我们可以用现有的设备测量这些电路中不同节点的突触效率。使用这一策略，我们将能够测量同一只小鼠的突触、神经回路和行为水平的变化。与这笔赠款相关的培训还将为受训人员提供一个学习尖端技术的独特机会，使他们在学术、生物技术或工业研究领域的职业生涯中具有很高的市场竞争力。

A substantial number of Canadians are obese and have trouble regulating their food intake. Difficulties in regulating food intake derive from an increased motivation to consume food and a decreased ability to inhibit food intake. My laboratory primarily focuses on dopamine neurons of the ventral tegmental area (VTA), which encode the learning of cues that predict rewards and increased motivation to obtain food driven by their output in target structures, such as the striatum. The overarching goal of the research program is to delineate neural circuits underlying changes in motivational state and decision-making and determine the neuroadaptations associated with increased food intake in nodes of these circuits. Glutamatergic inputs to the VTA dopaminergic neurons modulate learning of food-related cues. Furthermore, circuits within the cortex and their projections to the striatum may be implicated in deciding whether or not to eat. Using a combination of pharmacology and patch-clamp electrophysiology, we have made significant progress in determining how synaptic strength within nodes of these circuits varies with satiety state signaled by hormones or neuropeptides. We are now at a critical stage of the project where we need to understand how these mechanisms work in a pathophysiological circumstance. Indeed, aberrant motivation for food resulting in increased food intake can lead to alterations in cognitive behaviors including decision-making and impulsivity. This proposal is for funds to purchase a touch screen system to measure cognitive behaviors in mice so that, in combination with optogenetics, we can dissociate the contribution of different circuits underlying the learning of cues that predict rewards, decision making, and impulsivity. After behavioral assessment with the Bussey-Saksida chambers, we can then measure synaptic efficacy at different nodes within these circuits with our existing equipment. Using this strategy, we will be able to measure changes at the synaptic, neural circuit and behavioural level in the same mouse. Training associated with this grant will also provide a unique opportunity for trainees to learn a cutting-edge technology making them highly marketable for careers in academic, biotechnological or industrial research.