AMPA Silencing Is a Prerequisite for Developmental Long-Term Potentiation in the Hippocampal CA1 Region
AMPA Silencing Is a Prerequisite for Developmental Long-Term Potentiation in the Hippocampal CA1 Region
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DOI：
10.1152/jn.90476.2008
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发表时间：
2008-11-01
影响因子：
2.5
通讯作者：
Hanse, Eric
中科院分区：
文献类型：
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作者：
Abrahamsson, Therese;Gustafsson, Bengt;Hanse, Eric
AMPA沉默是海马CA1区发育长期增强的先决条件。中国生物医学工程学报（英文版），2009,31(4):559 - 564。首次发表于2008年9月7日；doi: 10.1152 / jn.90476.2008。AMPA （α -氨基-3-羟基-5-甲基-4-异唑烯丙酸）解除沉默是一种经常被提出的表达机制，既涉及发育长期增强（LTP），参与大脑发育过程中的电路完善，也涉及成熟的LTP，参与学习和记忆。在海马CA3-CA1连接中，初始（非刺激）突触是AMPA信号传导，AMPA沉默突触是由初始AMPA信号传导（AMPA不稳定）突触通过测试脉冲突触激活（AMPA沉默）产生的。为了研究不同发育阶段的LTP在多大程度上可以通过AMPA的沉默来解释，在这些不同发育阶段获得的LTP的数量与诱导LTP之前AMPA沉默的数量有关。当在出生后第二周进行检查时，发现Hebbian诱导产生的稳定增强并不比导致AMPA沉默之前存在的原始突触强度的增强更稳定。此外，在没有AMPA沉默的情况下，Hebbian诱导不会产生高于初始突触强度的稳定增强。因此，这种早期或发展性LTP只不过是AMPA信号的解除沉默（抑郁）和稳定，而AMPA信号因先前的AMPA沉默而丢失。这种AMPA信号的抑制和稳定被蛋白激酶A激活剂forskolin的存在所模拟。随着AMPA沉默的相对程度随着发育而降低，LTP越来越多地表现为“真正的”增强（而不是抑郁），而不是AMPA不稳定突触的沉默和稳定。这种“真正的”或成熟的LTP从出生后第13天(P)之前几乎没有总LTP，到第16天(P)时约占总LTP的70%，到第30天(P)时约占总LTP的90%。发育性LTP通过稳定ampa不稳定的突触，因此似乎适应于选择突触连接到生长的突触网络。成熟的LTP通过加强细胞之间现有的稳定连接，可能在该网络中创建功能紧密连接的细胞组件。
Abrahamsson T, Gustafsson B, Hanse E. AMPA silencing is a prerequisite for developmental long-term potentiation in the hippocampal CA1 region. J Neurophysiol 100: 2605-2614, 2008. First published September 7, 2008; doi:10.1152/jn.90476.2008. AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) unsilencing is an often proposed expression mechanism both for developmental long-term potentiation (LTP), involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3-CA1 connection naive (non-stimulated) synapses are AMPA signaling and AMPA-silent synapses are created from naive AMPA-signaling (AMPA-labile) synapses by test-pulse synaptic activation (AMPA silencing). To investigate to what extent LTP sat different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naive synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naive synaptic strength. Thus this early, or developmental, LTP is nothing more than an unsilencing (dedepression) and stabilization of the AMPA signaling that was lost by the prior AMPA silencing. This dedepression and stabilization of AMPA signaling was mimicked by the presence of the protein kinase A activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a "genuine" potentiation (as opposed to a dedepression) not explained by unsilencing and stabilization of AMPA-labile synapses. This "genuine," or mature, LTP rose from close to nothing of total LTP prior to postnatal day (P)13, to about 70% of total LTP at P16, and to about 90% of total LTP at P30. Developmental LTP, by stabilization of AMPA-labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.