Motor Systems Supporting Pavlovian Conditioning

描述(申请人提供)：本研究项目的长期目标是确定负责产生光诱导的纤毛运动和反射引起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和改变回路中固有的细胞兴奋性。这项资助中提议的实验将为巴甫洛夫条件反射如何改变神经回路以支持两种条件反应的产生提供洞察力：CS诱导的足部收缩和光诱导的运动的条件抑制。为了实现这些目标，将在海洋软体动物Hermissanda中开展多学科方法来研究光诱导的纤毛运动和足部收缩的细胞和突触基础；这种准备已被证明在学习的生物物理、生化和分子研究中有用。其中一个主要目标将是利用电压钳技术分析有助于增强条件化动物中间神经元内在兴奋性的电导。我们还将进一步确定回路中的神经元，这些神经元支持光诱导的纤毛运动和反射引起的足后部收缩。使用分离的神经系统、完整的动物和半完整的准备，我们将识别电路的神经元件，并确定该网络的特性如何有助于产生光诱导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来改变。我们将在记录中间神经元和踏板运动神经元的同时，在半完整的准备中检查纤毛激活和他汀囊引起的足部收缩。从已识别的光感受器和毛细胞接受感觉输入，并投射到纤毛激活和足部收缩的中间神经元将被识别和表征。我们将研究对条件化动物I型多感觉中间神经元的突触输入，以确定巴甫洛夫条件反射如何在不增加I型中间神经元对其他感觉输入的反应性的情况下，改变由条件刺激(CS)介导的一种感觉输入。这种实验方法将通过在支持行为产生的神经回路中识别由条件作用产生的其他潜在的可塑性位点来扩大我们对Hermissenda中的条件反射的理解，并为理解特定于一种模式的内在细胞和突触修改如何在也必须支持正常多感觉加工的回路中表达提供数据库。这些研究将有助于阐明多感官神经系统组织、产生行为及其通过学习进行修改的一般原理。

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.