Schwyzer Lucia, Mateos José María, Abegg Mathias, Rietschin Lotty, Heeb Lucette, Thompson Scott M, Lüthi Andreas, Gähwiler Beat H, McKinney R Anne
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Eur J Neurosci. 2002 Nov;16(10):1939-48. doi: 10.1046/j.1460-9568.2002.02259.x.
Expression of neurotrophins (NTs) and their receptors is elevated in the adult CNS under several neuropathological conditions. We have investigated the anatomical and electrophysiological consequences of chronic NT-3 or NT-4/5 treatment on established organotypic hippocampal slice cultures maintained in vitro for > 14 days. Both NT-3 and NT-4/5 increased spontaneous, action potential-dependent excitatory synaptic activity (sEPSCs), but only NT-3 increased inhibitory synaptic activity (sIPSCs) in CA3 pyramidal cells. Both NTs strongly promoted spontaneous synaptic bursting activity. Spontaneous bursts of EPSCs were observed after either NT treatment but only NT-3-treated cultures exhibited an increase in spontaneous bursts of IPSCs. In addition, sIPSC bursts were eliminated by blocking glutamatergic excitation. The frequency of miniature inhibitory postsynaptic currents, but not miniature excitatory postsynaptic currents, was also increased by both NT-3 and NT-4/5. Furthermore, NT-3 and NT-4/5 induced an up-regulation of the growth-associated protein GAP-43, suggesting that neurotrophins may be able to induce axonal reorganization in established neuronal networks. CA1 pyramidal cells exhibited slight alterations in dendritic branching after NT-4/5, but not NT-3 treatment. We conclude that chronic treatment with NT-3 or NT-4/5 can affect an established hippocampal network by elevating spontaneous inhibitory and excitatory synaptic activity and inducing coordinated pre- and postsynaptic structural changes.
在几种神经病理条件下，神经营养因子（NTs）及其受体在成体中枢神经系统中的表达会升高。我们研究了慢性给予NT-3或NT-4/5对体外维持超过14天的成熟海马脑片培养物的解剖学和电生理学影响。NT-3和NT-4/5均增加了自发的、动作电位依赖性的兴奋性突触活动（sEPSCs），但只有NT-3增加了CA3锥体神经元的抑制性突触活动（sIPSCs）。两种神经营养因子均强烈促进自发突触爆发活动。给予任何一种神经营养因子处理后均观察到EPSCs的自发爆发，但只有经NT-3处理的培养物中IPSCs的自发爆发增加。此外，通过阻断谷氨酸能兴奋消除了sIPSC爆发。NT-3和NT-4/5还增加了微小抑制性突触后电流的频率，但未增加微小兴奋性突触后电流的频率。此外，NT-3和NT-4/5诱导生长相关蛋白GAP-43上调，提示神经营养因子可能能够在成熟神经元网络中诱导轴突重组。NT-4/5处理后CA1锥体神经元的树突分支有轻微改变，但NT-3处理后未出现此现象。我们得出结论，慢性给予NT-3或NT-4/5可通过提高自发抑制性和兴奋性突触活动以及诱导突触前和突触后结构的协调变化来影响成熟的海马网络。
