Motor Systems Supporting Pavlovian Conditioning

描述（由申请人提供）：本研究项目的长期目标是确定负责产生光引发的纤毛运动和反射引发的足部收缩的神经回路;并了解巴甫洛夫条件反射如何改变神经元之间的突触连接并改变回路中的内在细胞兴奋性。在这项授权中提出的实验将提供深入了解如何通过巴甫洛夫条件反射来修改神经回路，以支持两种条件反应的产生; CS引起的足部收缩和光引起的运动的条件抑制。为了实现这些目标，一个多学科的方法来研究光引起的纤毛运动和脚收缩的细胞和突触基础将在海洋软体动物Hermissenda中进行;一种已被证明在生物物理，生物化学和分子学习研究中有用的制剂。一个主要的目标将是分析电导，有助于提高内在兴奋性的条件动物使用电压钳技术的中间神经元。我们还将进一步识别支持光诱导的纤毛运动和反射诱导的后足收缩的神经元。使用孤立的神经系统，完整的动物和半完整的制剂，我们将确定电路的神经元，并确定网络的属性如何有助于产生光引起的纤毛运动和反射引起的足部收缩。第二个主要目标是确定支持运动和反射引起的足部收缩的回路如何通过巴甫洛夫条件反射进行修改。我们将检查纤毛激活和平衡囊引起的足收缩在半完整的准备，同时记录从中间神经元和足运动神经元。将识别和表征从识别的光感受器和毛细胞接收感觉输入并投射到纤毛激活和足收缩足运动神经元的中间神经元。我们将研究突触输入到条件动物的多感觉I型中间神经元，以确定巴甫洛夫条件反射如何修改一个感觉输入，由条件刺激（CS）介导，而不增加I型中间神经元对其他感觉输入的反应。这种实验方法将扩大我们对Hermissenda条件反射的理解，通过识别支持行为产生的神经回路，由条件反射产生的可塑性的其他潜在位点，并提供数据库，以了解如何在还必须支持正常多感觉处理的回路中表达特定于一种模态的内在细胞和突触修饰。这些研究将有助于阐明产生行为的多感觉神经系统的组织及其通过学习进行修改的一般原则。

DESCRIPTION (provided by applicant): The long-term objective of this research project is to identify the neural circuit that is responsible for the generation of light-elicited ciliary locomotion and reflex-elicited foot contraction; and to understand how Pavlovian conditioning changes synaptic connections between neurons and alters intrinsic cellular excitability in the circuit. The experiments proposed in this grant will provide insights into how a neural circuit can be modified by Pavlovian conditioning to support the generation of two conditioned responses; CS-elicited foot contraction and conditioned inhibition of light-elicited locomotion. To achieve these goals, a multidisciplinary approach to the study of the cellular and synaptic basis of light-elicited ciliary locomotion and foot contraction will be carried out in the marine mollusk Hermissenda; a preparation that has proven useful in biophysical, biochemical, and molecular studies of learning. One primary goal will be to analyze conductances that contribute to the enhanced intrinsic excitability of the interneurons of conditioned animals using voltage-clamp techniques. We will also further identify neurons in the circuit that supports the generation of light-elicited ciliary locomotion and reflex-elicited contraction of the posterior foot. Using isolated nervous systems, intact animals and semi-intact preparations, we will identify the neural elements of the circuit and determine how the properties of the network contribute to the generation of light-elicited ciliary locomotion and reflex-elicited foot contraction. A second major goal is to determine how the circuit supporting locomotion and reflex-elicited foot contraction can be modified by Pavlovian conditioning. We will examine ciliary activation and statocyst-elicited foot contraction in semi-intact preparations while recording from interneurons and pedal motor neurons. Interneurons that receive sensory input from identified photoreceptors and hair cells, and project to cilia-activating and foot contraction pedal motor neurons will be identified and characterized. We will examine synaptic input to polysensory type I interneurons of conditioned animals to determine how Pavlovian conditioning modifies one sensory input, mediated by the conditioned stimulus (CS), without increasing the responsiveness of the type I interneurons to other sensory inputs. This experimental approach will expand our understanding of conditioning in Hermissenda by identifying within the neural circuit supporting the generation of behavior, other potential loci of plasticity produced by conditioning and provide the database for understanding how intrinsic cellular and synaptic modifications specific to one modality can be expressed in a circuit that must also support normal polysensory processing. These studies will help to elucidate general principles underlying the organization of polysensory neural systems generating behavior and their modification by learning.