Collingridge G L, Randall A D, Davies C H, Alford S
Department of Pharmacology, University of Birmingham, Medical School, Edgbaston, UK.
Ciba Found Symp. 1992;164:162-71; discussion 172-5. doi: 10.1002/9780470514207.ch11.
Long-term potentiation (LTP) in the hippocampus is a model system for understanding the synaptic basis of learning and memory. We have studied the mechanism of induction of LTP using voltage-clamp techniques and confocal imaging of Ca2+ in rat hippocampal slices. In the Schaffer collateral-commissural pathway the neurotransmitter L-glutamate activates two classes of ionotropic receptor, named after the selective ligands AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) and NMDA (N-methyl-D-aspartate). During low frequency transmission the excitatory postsynaptic potential (EPSP) is mediated predominantly by AMPA receptors. NMDA receptors play a minor role because their ion channels are substantially blocked by Mg2+, and this block is intensified by GABA-mediated synaptic inhibition. During high frequency transmission the GABA-mediated inhibition is depressed, by mechanisms initiated by GABAB autoreceptors. This allows a greater contribution from the NMDA receptors, through which Ca2+ enters the dendrites of the postsynaptic neurons to initiate a cascade of biochemical processes which ultimately result in enhanced synaptic efficiency.
海马体中的长时程增强（LTP）是理解学习和记忆突触基础的一个模型系统。我们利用电压钳技术和对大鼠海马切片中Ca2+的共聚焦成像研究了LTP的诱导机制。在海马的Schaffer侧支-连合通路中，神经递质L-谷氨酸激活两类离子型受体，它们以选择性配体AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）和NMDA（N-甲基-D-天冬氨酸）命名。在低频传递过程中，兴奋性突触后电位（EPSP）主要由AMPA受体介导。NMDA受体起次要作用，因为它们的离子通道被Mg2+大量阻断，并且这种阻断因GABA介导的突触抑制而增强。在高频传递过程中，GABA介导的抑制通过GABAB自身受体启动的机制而受到抑制。这使得NMDA受体有更大的贡献，Ca2+通过NMDA受体进入突触后神经元的树突，启动一系列生化过程，最终导致突触效率提高。
