Homeostatic regulation of mossy fiber-CA3 synapses in mature hippocampal gain con

成熟海马增益控制中苔藓纤维-CA3突触的稳态调节

• 批准号: 8529217
• 负责人: BN Queenan
• 金额: $ 2.78万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529217
• 关键词: AMPA Receptors; Acute; Adult; Agonist; Behavior; Biological Assay; Biological Neural Networks; Cells; Chronic; Complex; Confocal Microscopy; Control Locus; Data; Dendritic Spines; Distal; Epilepsy; Epileptogenesis; Excitatory Synapse; Feedback; Fiber; Frequencies; Hippocampus (Brain); Hyperactive behavior; In Vitro; Individual; Information Storage; Learning; Light; Location; Measures; Mediating; Memory; Morphology; Mus; Nerve Degeneration; Neuraxis; Neurologic Dysfunctions; Neurons; Pathogenesis; Physiology; Predisposition; Probability; Proteins; Pyramidal Cells; RNA Interference; Recycling; Regulation; Scaffolding Protein; Slice; Structure; Synapses; Synaptic plasticity; Temporal Lobe Epilepsy; Testing; Up-Regulation; Vertebral column; afadin; base; biocytin; cell type; dentate gyrus; granule cell; hippocampal pyramidal neuron; immunocytochemistry; in vivo; metabotropic glutamate receptor 2; mossy fiber; nerve supply; nervous system disorder; novel; patch clamp; postsynaptic; presynaptic; prevent; reconstruction; response; transmission process; vector

DESCRIPTION (provided by applicant): Individual neurons have been shown to homeostatically alter the strength of their excitatory connections in response to network activity: chronic inactivity induces compensatory increases in synaptic efficacy, while chronic hyperactivity induces compensatory decreases in synaptic efficacy. In fact, the negative feedback loops of homeostatic synaptic plasticity (HSP) are thought to be essential for the stability of neurons and neural networks. However, associative, or Hebbian, synaptic plasticity, which is thought to underlie learning and memory, is proposed to proceed via positive feedback-based changes in synaptic strength. It is therefore unclear how homeostatic synaptic adaptation can occur in established neuronal networks without threatening Hebbian information storage. Using both morphological and functional analysis, we have observed that HSP in mature hippocampal neurons in vitro occurred preferentially at proximal synapses. The mechanism of proximal adaptation consisted of the activity-dependent formation and elimination of large, multi-lobed dendritic spines which morphologically, biochemically, and pharmacologically resemble "thorny excrescences." Thorny excrescences, the complex proximal spines of CA3 pyramidal neurons in vivo, receive innervation from equally large presynaptic dentate gyrus (DG) mossy fiber terminals. The precise function of the highly specialized synapses between DG and CA3 neurons has remained enigmatic since their discovery over a century ago. We hypothesize that these synapses are the homeostatic "gain control locus" for not only mature hippocampal CA3 neurons, but for intact hippocampal networks. We therefore propose to investigate whether homeostatic synaptic adaptation occurs preferentially at mossy fiber-CA3 synapses. We will use a two-pronged functional and morphological approach to test this hypothesis both in vitro and in vivo.

描述（由申请人提供）：单个神经元已被证明可以动态地改变其兴奋性连接的强度，以响应网络活动。