Thiels E, Xie X, Yeckel M F, Barrionuevo G, Berger T W
Department of Neuroscience, University of Pittsburgh, Pennsylvania, USA.
Hippocampus. 1996;6(1):43-51. doi: 10.1002/(SICI)1098-1063(1996)6:1<43::AID-HIPO8>3.0.CO;2-8.
In simulations with artificial neural networks, efficient information processing and storage has been shown to require that the strength of connections between network elements has the capacity to both increase and decrease in a use-dependent manner. In contrast to long-term potentiation (LTP) of excitatory synaptic transmission, activity-dependent long-term depression (LTD) has been difficult to demonstrate in forebrain in vivo. Theoretical arguments indicate that coincidence of presynaptic excitation and low-magnitude postsynaptic activation are the necessary prerequisites for LTD induction. Here we report that stimulation paradigms which cause 1) sufficient excitation to result in NMDA receptor activation and simultaneously 2) attenuate the level of postsynaptic activation by recruitment of GABAA receptor-mediated inhibition consistently produce LTD of commissural input to area CA1 in the hippocampus of anesthetized adult rats, and of the perforant path input to the dentate gyrus in the hippocampus of anesthetized and unanesthetized adult rabbits. A functionally similar pre- and postsynaptic activation pattern applied to the hippocampal slice preparation by injecting hyperpolarizing current into the postsynaptic cell during NMDA receptor-mediated excitation also was effective in consistently inducing LTD. Results of studies in vitro show that Ca2+ influx through the NMDA channel is necessary for the induction of LTD, and moreover, that NMDA receptors also participate in the expression of LTD. Our findings demonstrate a general mechanism for the implementation of a theoretically derived learning rule in adult forebrain in vivo and in vitro and provide justification for the inclusion of use-dependent decreases of connection weights in formal models of cognitive processing.
在人工神经网络模拟中，已表明高效的信息处理和存储要求网络元件之间连接的强度能够以使用依赖的方式增加和减少。与兴奋性突触传递的长时程增强（LTP）相反，活动依赖的长时程抑制（LTD）在体内前脑一直难以得到证实。理论论证表明，突触前兴奋与低幅度突触后激活的同时发生是LTD诱导的必要前提。在此我们报告，刺激模式若能导致1）足够的兴奋以激活NMDA受体，同时2）通过募集GABAA受体介导的抑制来减弱突触后激活水平，则能持续在成年麻醉大鼠海马体中诱导连合输入至CA1区的LTD，以及在成年麻醉和未麻醉家兔海马体中诱导穿通通路输入至齿状回的LTD。在NMDA受体介导的兴奋过程中，通过向突触后细胞注入超极化电流，将功能相似的突触前和突触后激活模式应用于海马切片标本，也能有效地持续诱导LTD。体外研究结果表明，通过NMDA通道的Ca2+内流是LTD诱导所必需的，而且，NMDA受体也参与LTD的表达。我们的研究结果证明了在成年前脑体内和体外实施理论推导的学习规则的一般机制，并为在认知加工的形式模型中纳入连接权重的使用依赖型降低提供了依据。
