Evolution of behavioural control in vertebrates

两栖动物和两栖动物的大脑显示出一种保守的一般组织模式，但有一些显著的差异。与哺乳动物和鸟类的情况相比，两栖动物的模式要简单得多，因为较大的神经元数量较少，核分裂较少。了解这种更简单的神经基质如何发挥作用，可以提供有关控制脊椎动物行为的核心大脑通路的有用机制信息。我的研究计划的长期目标是了解脊椎动物行为控制的神经机制的演变。我们最近在火腹蟾蜍（铃蟾东方）的工作表明，行为的持久性开发与猎物捕捉反应的扩展训练。蟾蜍捕食行为起初是灵活的，但随着训练的增加，它变得更加自动和持久，最终，不灵活。药物滥用还可以通过在特别长的一段时间内，也许是永久性地改变行为而产生持久性。然而，正在激烈辩论起作用的具体机制。虽然很少，但在两栖动物中使用滥用药物进行的研究表明，这些动物可能是研究药物对大脑和行为影响的基本机制的良好模型。在接下来的5年里，我建议研究火腹蟾蜍的行为持久性是否涉及行为控制的多个方面，并确定正常学习和药物暴露导致的持久性所涉及的神经通路。拟议的实验将首先调查安非他明暴露对猎物捕捉的影响，一个基本的动机行为，然后安非他明自我管理的影响。选择安非他明是因为其能够增强行为持久性。重点将放在通过药物相关线索产生行为持久性和控制的学习范式上。此外，恢复熄灭的猎物捕捉或药物寻求反应的药物相关的线索或吸毒状态将进行调查，以找出蟾蜍显示复发样行为。最后，调查的神经基板的行为持久性和安非他明的影响计划。后者将通过测量大脑中即刻早期基因的表达来研究，这可以用作神经元活动的间接测量。在整个实验过程中，分析将评估蟾蜍的一个子集是否容易受到安非他明的影响，从而模仿哺乳动物反复接触这种药物的脆弱性。从拟议的工作中得出的发现将有助于显着提高我们对脊椎动物奖励和习惯学习的基本机制的理解，并确定它们如何/是否与药物作用有关。此外，这项工作可以提高我们对大脑中进化创新如何与脊椎动物行为能力相关的知识，这是一个知之甚少的问题。

Amphibian and amniote brains display a conserved general pattern of organization with a few notable differences. The amphibian pattern is much simpler due to a smaller number of larger neurons and less nuclear divisions compared to the situation in mammals and birds. Understanding how this simpler neural substrate functions could provide useful mechanistic information about the core brain pathways controlling behaviour in vertebrates. The long-term goal of my research program is to understand the evolution of neural mechanisms of behavioural control in vertebrates. Our recent work in the fire-bellied toad (Bombina orientalis) showed that behavioural persistence developed with extended training of a prey catching response. Toad prey catching behaviour was at first flexible, but with increased training it became more automatic and persistent, and ultimately, inflexible. Drugs of abuse can also produce persistence by altering behaviour for an exceptionally long period of time, perhaps permanently. However, the specific mechanisms at play are under intense debate. Although sparse, the research done using drugs of abuse in amphibians suggests that these animals could be good models to investigate the basic mechanisms of drug effects on brain and behaviour. Over the next 5 years, I propose to investigate if the behavioural persistence seen in the fire-bellied toad engages multiple aspects of behaviour control and to identify the neural pathways involved in persistence that results from normal learning and drug exposure. The proposed experiments will first investigate the effects of amphetamine exposure on prey catching, a basic motivated behaviour, and then the effects of amphetamine self-administration. Amphetamine is chosen for its ability to enhance behavioural persistence. Emphasis will be on learning paradigms that produce behavioural persistence and control by drug-associated cues. Additionally, reinstatement of extinguished prey catching or drug-seeking responses by drug-associated cues or a drugged state will be investigated to find out if toads display relapse-like behaviour. Finally, investigation of the neural substrate of behavioural persistence and amphetamine effects is planned. The latter will be investigated by measuring the expression of immediate-early genes in the brain, which can be used as an indirect measure of neuronal activity. Throughout the experiments, analyses will assess if a subset of toads are vulnerable to amphetamine effects, thereby mimicking the vulnerability seen in mammals repeatedly exposed to this drug. The findings derived from the proposed work will help to significantly improve our understanding of the basic mechanisms of reward and habit learning in vertebrates, and determine how/if they relate to drug effects. Further, this work could improve our knowledge of how evolutionary innovations in the brain relate to behavioural capacities across vertebrates, something that is poorly understood.