Nonassociative and Associative Neuroplasticity

非联想和联想神经可塑性

基本信息

批准号：
7389721
负责人：
Thomas W Abrams
金额：
$ 30.64万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-30 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7389721
关键词：
Action Potentials Adenylate Cyclase Afferent Neurons Animals Antibodies Aplysia Attention Behavioral Binding Calcium Calmodulin Chromosome Pairing Conditioned Stimulus Decision Making Depressed mood Development Disease Dominant-Negative Mutation Drosophila genus Enzymes Equilibrium Event Fire - disasters Homosynaptic Depression Human Individual Learning Lipids Localized Maintenance Mammals Marines Mediating Mental Depression Modeling Modification Molecular Monomeric GTP-Binding Proteins Motor Neurons Mus Neuronal Plasticity Neurons Neurotransmitters Pain Pathway interactions Pattern Peptides Phosphatidic Acid Phospholipase D Phospholipids Play Process Protein Isoforms Protein Kinase C Proteins RNA Interference Reflex action Research Research Personnel Role Running Sensory Serotonin Signal Transduction Site Snails Stimulus Synapses Synaptic Transmission Synaptic plasticity Testing Thinking Training Vesicle Withdrawal analog base classical conditioning conditioning detector insight millisecond postsynaptic presynaptic prevent programs receptor research study response rho synaptic depression transmission process

项目摘要

DESCRIPTION (provided by applicant): We are studying activity-dependent forms of synaptic modification that are important in the representation of stimuli in the CNS during learning. It has long been hypothesized that the dually-regulated, calcium/calmodulin-sensitive adenylyl cyclase enzyme plays a role in associative learning in the marine snail Aplysia, in fruit flies and in mammals. Although this enzyme has been shown to be critical in learning in both Drosophila and mice, it has been difficult to directly explore the hypothesis that calmodulin-sensitive adenylyl cyclase serves as a molecular coincidence detector, integrating the cellular signals Ca and modulator/ neurotransmitter. We have now cloned three isoforms of adenylyl cyclase in Aplysia, including one that binds to and is stimulated by calmodulin. In cellular electrophysiological experiments we will test the role of convergent activation of this adenylyl cyclase in associative synaptic strengthening during conditioning. During conditioning, the associative synaptic modification enhances the importance of particular stimuli for the animal. Non-associative activity-dependent plasticity also plays an essential role in learning, determining which stimuli receive effective attention. This is critical in the context of learning, because without appropriate afferent transmission of information about stimuli, learning is not possible. In the activation of Hebbian mechanisms of synaptic strengthening during learning, it is essential that afferent input successfully activate the postsynaptic neurons. We are analyzing an activity-dependent switch that can either shut off or maintain synaptic transmission in a sensory pathway, depending on the precise pattern of sensory neuron activity. This switch involves activity-dependent, calcium-mediated activation of protein kinase C, precisely localized to presynaptic transmitter release sites. The pathway that is regulated in an activity-dependent manner appears to involve phospholipid synthesis and the small GTPase ARF. We will explore the molecular steps in this pathway, using RNAi, dominant-negative proteins and caged lipids. These studies are relevant for both for learning and for attention disorders.

描述（由申请人提供）：我们正在研究在学习过程中刺激中CNS中刺激的代表的突触修饰形式。长期以来，人们一直认为，双重调节的，钙/钙调蛋白敏感的腺苷酸环化酶酶在海洋蜗牛腹泻，水果蝇和哺乳动物中起作用。尽管该酶在果蝇和小鼠中都至关重要，但很难直接探索钙调蛋白敏感蛋白敏感的腺苷酸环酶作为分子巧合探测器的假设，从而整合了细胞信号CA和调节剂/神经递质。现在，我们已经克隆了三种腺苷环酶的三种同工型，其中包括与钙调蛋白结合并刺激的同工型。在细胞电生理实验中，我们将测试该腺苷酸环化酶在调节过程中联想突触增强中的收敛激活的作用。在调节过程中，联想突触修饰增强了特定刺激对动物的重要性。非缔合活动依赖性可塑性在学习中也起着至关重要的作用，确定哪些刺激受到有效的关注。这在学习的背景下至关重要，因为如果没有适当的传播信息传播有关刺激的信息，就不可能学习。在学习过程中突触加强的Hebbian机制时，传入输入能够成功激活突触后神经元至关重要。我们正在分析一个与活动相关的开关，该开关可以取决于感觉神经元活性的精确模式，该开关可以关闭或保持感觉途径的突触传播。该开关涉及活性依赖性的，钙介导的蛋白激酶C的激活，该蛋白激酶C精确地定位于突触前发射器释放位点。以活性依赖性方式调节的途径似乎涉及磷脂合成和小的GTPase ARF。我们将使用RNAi，显性阴性蛋白和笼脂质探索该途径中的分子步骤。这些研究与学习和注意力障碍有关。