Cellular bases of noncoincidence learning in Hermissenda

Hermissenda 中非巧合学习的细胞基础

• 批准号: 7031768
• 负责人: JOSEPH FARLEY
• 金额: $ 24.73万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031768
• 关键词: Hermissenda; afferent nerve; aminopyridines; association learning; behavioral /social science research tag; biological signal transduction; calcium flux; calcium indicator; conditioning; membrane potentials; molecular psychobiology; neurophysiology; nonvisual photoreceptor; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): We will study cellular processes underlying non-coincidence learning and conditioned inhibition in the mollusk Hermissenda (H.c.). This fundamental, but poorly understood category of associative learning can be readily produced in H.c., by exposing animals to a classical conditioning procedure where light (the CS) signals the absence of rotation (the US). Explicitly unpaired (EU) presentations of light and rotation increase animals' phototactic behavior. We will continue to characterize the persistent excitability changes that are produced in Type B and A photoreceptors within the CS-pathway. We have found that ocular Type B cells from EU-trained, but not control-condition, animals exhibit persistent decreases in their steady-state depolarizing generator potentials (SSGPs), and decreases in light-evoked spike frequencies. We will complete our studies demonstrating that Type A cells show complementary changes with EU-training: increases in SSGPs and light-elicited spike frequency. The ionic bases of the changes in photoreceptor excitability will be studied using voltage-clamp, ion substitution, and pharmacological methods. We will complete our studies that indicate that the decreased excitability of B cells is due to persistent increases in somatic K+ currents (IA and IK-Ca), and further characterize the mechanisms responsible. The contribution of calcium-dependent processes to expression of B cell photoresponse changes will be studied, as well as the contribution of changes in IA to the EU decreases in spike frequency. We will also determine the ionic conductance changes responsible for the increased excitability of Type A cells. We will test for the occurrence of EU-produced changes in synaptic transmission between B-B and B-A photoreceptors, through simultaneous intracellular recordings from pre- and postsynaptic cells on retention days following learning. We will continue our studies of the induction of decreases in B cell excitability, through the use of an in vitro conditioning protocol, and will test for the involvement of calcium, protein phosphatase 1 (PP1), and arachidonic acid (AA) in the production of the EU-associated decreases in B cell excitability. Because temporally-varying [Ca2+]i levels may be a crucial factor as to whether B cells exhibit excitability decreases or increases due to different stimulation regimens involving light and rotation, we will measure B cell [Ca2+]i levels at different time points following light. Ratiometric fura-2 imaging methods will be used to see if the interstimulus intervals that result in successful EU-conditioning match a specific [Ca2+]i level.

描述（由申请人提供）：我们将研究软体动物 Hermissenda (H.c.) 中非巧合学习和条件抑制的细胞过程。这种基本但知之甚少的联想学习类别可以在 H.c. 中很容易地产生，方法是将动物暴露于经典的条件反射程序中，其中光（CS）表示不存在旋转（US）。明确不成对（EU）的光和旋转呈现会增加动物的趋光行为。我们将继续表征 CS 通路内 B 型和 A 型光感受器产生的持续兴奋性变化。我们发现，经过 EU 训练（而非对照条件）的动物眼部 B 型细胞的稳态去极化发生器电位 (SSGP) 持续降低，并且光诱发尖峰频率降低。我们将完成我们的研究，证明 A 型细胞在 EU 训练中表现出互补的变化：SSGP 和光引发的尖峰频率增加。将使用电压钳、离子取代和药理学方法来研究光感受器兴奋性变化的离子基础。我们将完成我们的研究，表明 B 细胞兴奋性降低是由于体细胞 K+ 电流（IA 和 IK-Ca）持续增加所致，并进一步描述其机制。将研究钙依赖性过程对 B 细胞光响应变化表达的贡献，以及 IA 变化对 EU 尖峰频率降低的贡献。我们还将确定导致 A 型细胞兴奋性增加的离子电导变化。我们将通过学习后保留天的突触前和突触后细胞的同步细胞内记录，测试 B-B 和 B-A 光感受器之间突触传递中 EU 产生的变化的发生情况。我们将继续研究通过使用体外调节方案诱导 B 细胞兴奋性降低，并将测试钙、蛋白磷酸酶 1 (PP1) 和花生四烯酸 (AA) 在生产中的参与情况EU 相关的 B 细胞兴奋性降低。由于随时间变化的 [Ca2+]i 水平可能是决定 B 细胞是否因涉及光和旋转的不同刺激方案而表现出兴奋性降低或增加的关键因素，因此我们将在光照射后的不同时间点测量 B 细胞 [Ca2+]i 水平。将使用比例 fura-2 成像方法来查看导致成功 EU 调节的刺激间隔是否与特定的 [Ca2+]i 水平相匹配。