MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

基本信息

批准号：
7230625
负责人：
REBEKAH J CORLEW
金额：
$ 2.7万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7230625
关键词：
AMPA Receptors Action Potentials Adolescent Adult Affect Age Amblyopia Animal Model Animals Belief Biological Assay Blindness Cells Child Chromosome Pairing Chronic Complex Condition Conflict (Psychology)Consensus Contralateral Cortical Blindness Coupled Darkness Data Depressed mood Development Diagnosis Disputes Down-Regulation Early Diagnosis Educational process of instructing Electrophysiology (science)Epilepsy Excitatory Amino Acid Antagonists Excitatory Postsynaptic Potentials Exhibits Eye Fellowship Program Fire - disasters Glutamate Receptor Glutamates Goals Hippocampus (Brain)Human Immunoelectron Microscopy In Vitro Infusion procedures Ipsilateral Lead Left Life Ligands Long-Term Depression Mediating Minority Modification Mus N-Methyl-D-Aspartate Receptors NR1 gene Names Neurons Neurotransmitters Numbers Ocular Dominance Pathway interactions Pattern Peripheral Phosphorylation Predisposition Pregnenolone Prevention Probability Procedures Property Puberty Publishing Pyramidal Cells Rate Rattus Recovery Regulation Relative (related person)Resistance Rodent Role Sensory Sensory Deprivation Shapes Site Slice Staging Strabismus Synapses Synaptic Transmission Synaptic plasticity Testing Thinking Time Vision research Visual Visual Cortex Visual system structure Week Whole-Cell Recordings Yang age effect base cannabinoid receptor critical developmental period dark rearing day deprivation detector entorhinal cortex excitatory neuron experience extracellular human NR1 protein insight monocular monocular deprivation mouse model neurotransmitter release novel postnatal postsynaptic pre-doctoral presynaptic prevent programs pup receptive field receptor receptor expression receptor function research study response sensory cortex somatosensory synaptic depression transmission process vision development visual deprivation visual receptive field

AMPA Receptors Action Potentials Adolescent Adult Affect Age Amblyopia Animal Model Animals Belief Biological Assay Blindness Cells Child Chromosome Pairing Chronic Complex Condition Conflict (Psychology)Consensus Contralateral Cortical Blindness Coupled Darkness Data Depressed mood Development Diagnosis Disputes Down-Regulation Early Diagnosis Educational process of instructing Electrophysiology (science)Epilepsy Excitatory Amino Acid Antagonists Excitatory Postsynaptic Potentials Exhibits Eye Fellowship Program Fire - disasters Glutamate Receptor Glutamates Goals Hippocampus (Brain)Human Immunoelectron Microscopy In Vitro Infusion procedures Ipsilateral Lead Left Life Ligands Long-Term Depression Mediating Minority Modification Mus N-Methyl-D-Aspartate Receptors NR1 gene Names Neurons Neurotransmitters Numbers Ocular Dominance Pathway interactions Pattern Peripheral Phosphorylation Predisposition Pregnenolone Prevention Probability Procedures Property Puberty Publishing Pyramidal Cells Rate Rattus Recovery Regulation Relative (related person)Resistance Rodent Role Sensory Sensory Deprivation Shapes Site Slice Staging Strabismus Synapses Synaptic Transmission Synaptic plasticity Testing Thinking Time Vision research Visual Visual Cortex Visual system structure Week Whole-Cell Recordings Yang age effect base cannabinoid receptor critical developmental period dark rearing day deprivation detector entorhinal cortex excitatory neuron experience extracellular human NR1 protein insight monocular monocular deprivation mouse model neurotransmitter release novel postnatal postsynaptic pre-doctoral presynaptic prevent programs pup receptive field receptor receptor expression receptor function research study response sensory cortex somatosensory synaptic depression transmission process vision development visual deprivation visual receptive field

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项目摘要

DESCRIPTION (provided by applicant): It is widely accepted that activation of the NMDA-type glutamate receptor (NMDAR) is required for experience-dependent strengthening and weakening of visual cortical synaptic connections. This plasticity occurs predominantly during a critical period of visual cortex development when visual receptive fields are being formed and refined. Some forms of NMDAR-mediated plasticity may be strictly confined to developmental time points. Other forms are sensitive to experience, where brief periods of sensory deprivation can alter the mechanisms as well as the capacity for NMDAR-dependent plasticity. Recent evidence suggests that presynaptic NMDARs may have a unique role in this refinement, yet the developmental and experience-dependent regulation of presynaptic NMDARs have not been studied. To understand the role that presynaptic NMDARs have in visual receptive field refinement, we need to study their effects on synaptic plasticity during development and with altered visual experience. We will use electrophysiology and immuno-electron microscopy on mice at different stages of visual system development, raised with or without visual experience, to test three hypotheses formed by our preliminary findings. 1) There is a developmental decrease in the functional expression of presynaptic NMDARs, which increases glutamate release early in development. 2) The contribution of presynaptic NMDARs to release probability changes after visual deprivation in the adult, but dark rearing at younger stages does not. 3) These developmental and experience-dependent changes modify the properties of spike timing-dependent synaptic depression. There is a consensus that NMDARs are required for many types of plasticity in the visual system, but the mechanisms and limitations of this plasticity continue to be disputed. Our study will examine the possibility that the conflicting data on the role of NMDARs in plasticity may be explained by developmental differences in the expression of experience-dependent plasticity. Elucidating the involvement of pre- versus postsynaptic NMDARs in synaptic plasticity will provide insights into the eventual treatment of amblyopia and other conditions caused by the improper development of synaptic connections.

描述（由申请人提供）：广泛接受的是，NMDA型谷氨酸受体（NMDAR）的激活是依赖经验的增强和弱化视觉皮质突触连接所必需的。这种可塑性主要发生在形成和完善视觉接受场的关键时期。某些形式的NMDAR介导的可塑性可能严格仅限于发育时间点。其他形式对经验很敏感，其中短暂的感觉剥夺可以改变机制以及依赖NMDAR依赖性可塑性的能力。最近的证据表明，突触前NMDAR可能在这种完善中具有独特的作用，但是尚未研究突触前NMDAR的发展和经验依赖性调节。为了了解突触前NMDAR在视觉接受场的细化中的作用，我们需要研究它们对发育过程中突触可塑性的影响，并随着视觉体验的改变。我们将在视觉系统发育的不同阶段对小鼠进行电生理学和免疫电子显微镜，以测试我们的初步发现形成的三个假设。 1）突触前NMDAR的功能表达有所下降，这会在发育早期增加谷氨酸释放。 2）突触前NMDAR在成人视觉剥夺后释放概率变化的贡献，但在年轻阶段进行深度饲养。 3）这些发展和经验依赖性变化改变了峰值依赖性突触抑制的特性。有一个共识，即视觉系统中许多类型的可塑性需要NMDAR，但是这种可塑性的机制和局限性仍在争议中。我们的研究将研究有关NMDAR在可塑性中作用的相互冲突数据的可能性，可以通过经验依赖性可塑性的表达来解释。阐明前与突触后NMDAR参与突触可塑性的参与将为最终治疗弱视和其他疾病的洞察力提供见解。