Synaptic plasticity in young versus aged cortex

年轻皮层与老年皮层的突触可塑性

基本信息

批准号：
9891059
负责人：
Elizabeth Mary Quinlan
金额：
$ 40.71万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9891059
关键词：
5 year old Adult Age Amblyopia Animal Model Axon Biological Markers Blindness Clinical Clinical Treatment Data Development Electrophysiology (science)Environment Estrogen Replacements Family Felidae Fluorescence Gonadal Steroid Hormones Individual Instruction Interneurons Intuition Life Light MMP9 gene Matrix Metalloproteinases Mediating Metalloproteases Methods Modeling Molecular Genetics Monocular Vision Mus Neurons Pathway interactions Peptide Hydrolases Population Proteolysis Psychophysics Recovery Regulation Resistance Resolution Rodent Structure Supplementation Synapses Synaptic plasticity Testing Thalamic structure Time Translations Vision Visual Visual Acuity Visual Cortex Work aged area striata critical period experience extracellular functional plasticity in vivo in vivo two-photon imaging insight light effects morphometry optogenetics predictive modeling synaptogenesis tool visual deprivation

项目摘要

Project Summary The decline in synaptic plasticity with age is thought to impose severe constraints on the recovery from amblyopia in adults. Although this developmental loss was previously thought to be irreversible, our previous work established that robust plasticity can be reactivated in the adult visual cortex via visual deprivation by dark exposure. Furthermore, dark exposure followed by instructive visual experience enables complete recovery from severe amblyopia in adulthood. Our previous work assumed that the elimination of visual input during dark exposure was sufficient to reactivate plasticity. However, our preliminary data demonstrate that light reintroduction after dark exposure is responsible for the reactivation of structural and functional plasticity in the adult mouse visual cortex. We propose to show that LRx following dark exposure increases the activity of a key extracellular protease (matrix metalloprotease-9) at thalamic inputs to cortical neuron and a counter- intuitive decrease in the excitability of regular spiking neurons to reactivate robust plasticity in the adult dark- exposed cortex.

项目概要突触可塑性随年龄的下降被认为严重限制了神经元的恢复。成人弱视。尽管这种发育损失以前被认为是不可逆转的，但我们之前研究表明，通过视觉剥夺可以重新激活成人视觉皮层的强大可塑性黑暗曝光。此外，黑暗曝光和指导性视觉体验可以实现完整的成年后从严重弱视中恢复。我们之前的工作假设消除视觉输入在黑暗暴露期间足以重新激活可塑性。然而，我们的初步数据表明黑暗暴露后重新引入光线负责结构和功能可塑性的重新激活在成年小鼠的视觉皮层中。我们建议证明黑暗暴露后 LRx 会增加活性丘脑输入皮质神经元的关键细胞外蛋白酶（基质金属蛋白酶-9）和反作用常规尖峰神经元的兴奋性直观下降，以重新激活成人黑暗中的强大可塑性暴露的皮质。