Evolution of behavioural control in vertebrates

脊椎动物行为控制的进化

• 批准号: RGPIN-2014-06383
• 负责人: Laberge, Frederic
• 金额: $ 1.89万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631397
• 关键词: Evolution; behavioural; control; vertebrates

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.

两栖动物和羊膜动物的大脑显示出保守的总体组织模式，但有一些显著的差异。两栖动物的模式要简单得多，因为与哺乳动物和鸟类的情况相比，较少的较大神经元和较少的核分裂。了解这种更简单的神经底物是如何发挥作用的，可以为脊椎动物控制行为的核心大脑通路提供有用的机械信息。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进化。我们最近对火腹蟾蜍(Bombina Orientalis)的研究表明，行为持久力随着对猎物捕捉反应的长期训练而发展。起初，蟾蜍的捕食行为是灵活的，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。滥用药物还可以通过在非常长的一段时间内--可能是永久性的--改变行为，从而产生持久性。然而，具体的作用机制仍在激烈辩论中。尽管数量稀少，但在两栖动物身上使用滥用药物的研究表明，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，我建议调查在火腹蟾蜍身上看到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路径。拟议的实验将首先调查苯丙胺暴露对猎物捕捉的影响，这是一种基本的动机行为，然后调查苯丙胺自我给药的影响。安非他命之所以被选中，是因为它能够增强行为的持久性。重点将放在产生行为持久性和通过与药物相关的线索进行控制的学习范例上。此外，还将调查通过与毒品有关的线索或吸毒状态恢复已熄灭的猎物或寻找毒品的反应，以找出蟾蜍是否表现出复发的行为。最后，计划对行为持续性和苯丙胺效应的神经底物进行调查。后者将通过测量大脑中即刻早期基因的表达来进行研究，这可以作为神经元活动的间接测量。在整个实验过程中，分析将评估是否有一部分蟾蜍容易受到苯丙胺的影响，从而模仿反复接触这种药物的哺乳动物的脆弱性。这项拟议工作的发现将有助于显著提高我们对脊椎动物奖赏和习惯学习的基本机制的理解，并确定它们如何/是否与药物效果有关。此外，这项工作可以提高我们对大脑进化创新如何与脊椎动物的行为能力相关的知识，这一点人们知之甚少。