The effects of thalamoamygdalar synaptic potentiation on learning performance

丘脑杏仁核突触增强对学习表现的影响

• 批准号: 8063520
• 负责人: Kay Maxine Tye
• 金额: $ 5.05万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2012-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063520
• 关键词: Acute; Amygdaloid structure; Animal Housing; Animals; Aptitude; Area; Association Learning; Behavioral; Brain; Brain region; Calcium; Cannulas; Cell model; Chemosensitization; Cues; Dendrites; Electrodes; Electrophysiology (science); Environment; Fright; Glutamates; Gray unit of radiation dose; Growth; Implant; Information Storage; Laboratories; Lasers; Lateral; Learning; Left; Light; Long-Term Potentiation; Mediating; Membrane; Memory; Methods; Neurons; Outcome; Output; Pathway interactions; Performance; Population; Preparation; Presynaptic Terminals; Proliferating; Protocols documentation; Rattus; Recruitment Activity; Reporting; Research; Rewards; Sensory; Series; Signal Transduction; Site; Slice; Stimulus; Synapses; Synaptic plasticity; Testing; Tetanus; Thalamic structure; Time; Translating; Vertebral column; Work; behavior measurement; classical conditioning; density; experience; in vivo; interest; neurophysiology; neurotransmission; novel; patch clamp; research study; tool; trafficking

DESCRIPTION (provided by applicant): Long-term potentiation (LTP) is widely assumed to be the mechanism by which memory traces are encoded and stored (1-15). From Martin and colleagues, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." There is a great deal of evidence demonstrating that synaptic plasticity is necessary for learning and memory, but there is no convincing evidence supporting the notion of sufficiency (14). While numerous studies have shown that certain types of learning can occlude LTP in relevant brain regions (10-13,15-20), LTP has yet to be proven to occlude learning. Until now, technological limitations have precluded a convincing demonstration of LTP occlusion of learning, as delivering a tetanus with an electrode may have direct and indirect circuit-wide repercussions. With the recent advent and application of ChannelRhodopsin2 (ChR2) used in vivo (21-23) by the Deisseroth laboratory, where I will be working, and other groups, the tools are now available to selectively induce LTP into a specific subset of synapses thought to be important for associative learning. I hypothesize that selectively inducing LTP in the thalamo- amygdala pathway by using ChR2 will first occlude acquisition of a cue-outcome association, but will subsequently enhance the basal capacity of this pathway to be potentiated, thereby enhancing the aptitude for associative learning. I will test this hypothesis by first (Specific Aim 1) developing a novel method of inducing LTP in a specific subset of synapses using ChR2, and then by (Specific Aim 2) testing the learning ability of these rats at various time points after ChR2-LTP induction. These experiments will allow us to draw conclusions about the time course of the neurophysiological changes that mediate memory formation and storage with confidence

描述（由申请人提供）：长期增强（LTP）被广泛认为是编码和存储记忆迹线的机制（1-15）。从马丁及其同事中，突触可塑性和记忆假设指出，“在记忆形成过程中，在适当的突触下诱导了活动依赖性突触可塑性，并且对于观察到可变性的大脑区域介导的记忆类型的基础的信息既是必要且足够的信息。”有大量证据表明，突触可塑性对于学习和记忆是必要的，但是没有令人信服的证据支持足够的概念（14）。尽管大量研究表明，某些类型的学习可以在相关的大脑区域（10-13,15-20）遮住LTP，但LTP尚未证明可以阻塞学习。到目前为止，技术局限性排除了LTP学习的令人信服的证明，因为用电极提供破伤风可能会具有直接和间接的范围内电路范围的影响。随着Deisseroth Laboratory在体内使用的ChannelRhodopsin2（CHR2）的最新出现和应用，我将在这里工作，而其他组则可以选择地将LTP诱导到特定的突触子集中，这些突触被认为对关联学习很重要。我假设通过使用CHR2选择性地诱导LTP在丘脑杏仁核途径中，将首先遮挡提示结果关联的采集，但随后将增强该途径的基础能力，从而增强了该途径的能力，从而增强了社会学习能力。我将通过（特定目标1）使用CHR2的特定突触子集中诱导LTP，然后通过（特定目标2）测试这些大鼠在CHR2-LTP诱导后的各个时间点测试这些大鼠的学习能力。这些实验将使我们能够得出关于神经生理变化的时间过程的结论