在双向突触可塑性期间,对不同的AMPA受体酸化位的调节
H K Lee1, M Barbarosie, K Kameyama
1Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins Medical School, Baltimore, Maryland, USA.
Nature
|July 6, 2000
概括
与长期强化 (LTP) 和抑郁 (LTD) 一样,突触可塑性涉及AMPA受体酸化. 这些过程根据先前的突触活动改变了GluR1亚单元上的不同位置,揭示了依赖历史的信号通路.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 突触性可塑性 突触性可塑性
背景情况:
- 神经突触传输效率的变化,包括海马长期增强 (LTP) 和长期抑郁 (LTD),对于大脑信息存储至关重要.
- 假设AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazloe propionic acid) 受体酸化的调节可以调节LTP和LTD.
研究的目的:
- 研究AMPA受体GluR1亚单元酸化在LTP和LTD中的作用.
- 确定LTP和LTD是否涉及相同酸化位点或不同的位点的逆调制.
- 探索突触史对在LTP和LTD期间激活的信号通路的影响.
主要方法:
- 在LTP和LTD期间研究了AMPA受体GluR1亚单元酸化的可逆变化.
- 检查了与LTP和LTD诱导相关的酸化位点特异性.
- 研究了先前突触强化或抑郁对后续可塑性诱导的影响.
- 根据突触史评估了LTP对CaMKII和PKA抑制剂的差异敏感性.
主要成果:
- LTP和LTD可逆地改变AMPA受体的GluR1亚单元酸化.
- LTP和LTD调节不同的GluR1酸化位,而不是相反的位点.
- 突触历史决定了哪些化位点被调节:LTD在原始突触中的PKA位点和潜在突触中的CaMKII位点进行了化.
- 在原始突触中,LTP诱导了CaMKII位点和压抑突触中的PKA位点的酸化.
- 对CaMKII和PKA抑制剂的LTP敏感性随着突触史而变化.
结论:
- AMPA受体酸化对于突触可塑性至关重要.
- 突触可塑性机制不是简单的反向;它们涉及不同的酸化位点.
- 通过相同的刺激条件招募的信号传导通路取决于突触的先前活动历史.
相关概念视频
Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when presynaptic neurons...
Hebbian LTP
LTP can occur when presynaptic neurons...
Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...


