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.）的非巧合学习和条件抑制的细胞过程。这种基本的，但不为人所知的联想学习类别可以很容易地在h.c.中产生，通过将动物暴露在经典的条件反射过程中，光（CS）表示没有旋转（US）。明显的不配对（EU）光和旋转的表现增加了动物的趋光行为。我们将继续描述cs通路中B型和A型光感受器产生的持续兴奋性变化。我们发现，来自eu训练而非对照条件的动物的眼B型细胞表现出稳态去极化产生电位（SSGPs）的持续下降，以及光诱发峰频率的下降。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和光激发的尖峰频率增加。光感受器兴奋性变化的离子基础将使用电压钳、离子取代和药理学方法进行研究。我们将完成我们的研究，表明B细胞兴奋性的降低是由于体细胞K+电流（IA和IK-Ca）的持续增加，并进一步表征其机制。将研究钙依赖过程对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。我们将通过在学习后的保留日同时记录突触前和突触后细胞的细胞内记录，测试eu在B-B和B-A光感受器之间突触传递中产生的变化。我们将通过使用体外调节方案，继续我们对B细胞兴奋性降低的诱导研究，并将测试钙、蛋白磷酸酶1 （PP1）和花生四烯酸（AA）在eu相关的B细胞兴奋性降低的产生中的作用。由于时间变化的[Ca2+]i水平可能是B细胞是否表现出兴奋性降低或增加的关键因素，因为不同的刺激方案涉及光和旋转，我们将测量B细胞[Ca2+]i水平在不同的时间点光后。比率fura-2成像方法将用于观察导致成功的eu调节的间刺激间隔是否与特定的[Ca2+]i水平相匹配。