Burrone Juan, O'Byrne Michael, Murthy Venkatesh N
Department of Molecular & Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature. 2002 Nov 28;420(6914):414-8. doi: 10.1038/nature01242.
The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.
神经元活动导致中枢神经系统突触长期修饰的规则尚未完全明了。基于竞争或相关性的规则会导致突触的局部修饰，而稳态修饰则允许全神经元范围内突触强度的变化，从而促进稳定性。对中枢神经系统突触这些规则的实验研究通常依赖于操纵神经元群体的活动。在此，我们通过过表达内向整流钾通道来研究抑制活跃海马神经元网络中单个神经元兴奋性的影响。在突触形成之前降低神经元的活动会导致该神经元功能性突触输入的减少；当所有神经元的活动被均匀抑制时，则未观察到这种减少。相反，在突触建立后抑制单个神经元的活动会导致突触输入的稳态增加，从而将该神经元的活动恢复到对照水平。我们的结果突出了活动全局抑制与选择性抑制之间的差异，以及活动早期操纵与晚期操纵之间的差异。
