Evolution of behavioural control in vertebrates

两栖动物和羊膜动物的大脑显示出保守的一般组织模式，有一些显著的差异。与哺乳动物和鸟类相比，两栖动物的模式更简单，因为它们的大神经元数量更少，核分裂也更少。了解这种简单的神经基质如何发挥作用，可以提供有关脊椎动物控制行为的核心脑通路的有用机制信息。我的研究项目的长期目标是了解脊椎动物行为控制的神经机制的进化。我们最近对火腹蟾蜍（bomina orientalis）的研究表明，通过对猎物捕获反应的长期训练，行为持久性得以发展。蟾蜍捕捉猎物的行为起初是灵活的，但随着训练的增加，它变得更加自动和持久，最终变得不灵活。滥用药物也可以通过在很长一段时间内，也许是永久地改变行为而产生持久性。然而，起作用的具体机制正在激烈辩论中。尽管数量很少，但在两栖动物身上进行的药物滥用研究表明，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，我打算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获的影响，这是一种基本的动机行为，然后是安非他明自我服用的影响。选择安非他明是因为它能增强行为持久性。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例上。此外，通过药物相关线索或药物状态，将研究蟾蜍是否表现出类似复发的行为，从而恢复已灭绝的猎物捕获或寻求药物的反应。最后，研究行为持久性和安非他明效应的神经基质。后者将通过测量大脑中直接早期基因的表达来研究，这可以作为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易受安非他命的影响，从而模仿反复暴露于这种药物的哺乳动物的脆弱性。这项研究的结果将有助于我们更好地理解脊椎动物的奖励和习惯学习的基本机制，并确定它们是否与药物作用有关。此外，这项工作可以提高我们对大脑进化创新与脊椎动物行为能力之间关系的认识，这是我们知之甚少的。

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.