Cohen Eyal, Ivenshitz Miriam, Amor-Baroukh Veronique, Greenberger Varda, Segal Menahem
Department of Neurobiology, The Weizmann Institute, Rehovot, Israel.
Brain Res. 2008 Oct 15;1235:21-30. doi: 10.1016/j.brainres.2008.06.022. Epub 2008 Jun 19.
The brain generates extensive spontaneous network activity patterns, even in the absence of extrinsic afferents. While the cognitive correlates of these complex activities are being unraveled, the rules that govern the generation, synchronization and spread of different patterns of intrinsic network activity in the brain are still enigmatic. Using hippocampal neurons grown in dissociated cultures, we are able to study these rules. Network activity emerges at 3-7 days in-vitro (DIV) independent of either ongoing excitatory or inhibitory synaptic activity. Network activity matures over the following several weeks in culture, when it becomes sensitive to chronic drug treatment. The size of the network determines its properties, such that dense networks have higher rates of less synchronized activity than that of sparse networks, which are more synchronized but rhythm at lower rates. Large networks cannot be triggered to fire by activating a single neuron. Small networks, on the other hand, do not burst spontaneously, but can be made to discharge a network burst by stimulating a single neuron. Thus, the strength of connectivity is inversely correlated with spontaneous activity and synchronicity. In the absence of confirmed 'leader' neurons, synchronous bursting network activity appears to be triggered by at least several local subthreshold synaptic events. We conclude that networks of neurons in culture can produce spontaneous synchronized activity and serve as a viable model system for the analysis of the rules that govern network activity in the brain.
即使在没有外在传入神经的情况下，大脑也会产生广泛的自发网络活动模式。虽然这些复杂活动的认知关联正在被揭示，但大脑中内在网络活动不同模式的产生、同步和传播所遵循的规则仍然是个谜。利用在解离培养物中生长的海马神经元，我们能够研究这些规则。网络活动在体外培养3 - 7天（DIV）时出现，与持续的兴奋性或抑制性突触活动无关。在接下来的几周培养过程中，网络活动逐渐成熟，并对长期药物治疗变得敏感。网络的大小决定其特性，密集网络的活动同步性较低但频率较高，而稀疏网络的同步性较高但频率较低。激活单个神经元无法触发大型网络放电。另一方面，小型网络不会自发爆发，但通过刺激单个神经元可以使其产生网络爆发。因此，连接强度与自发活动和同步性呈负相关。在没有确定的“主导”神经元的情况下，同步爆发的网络活动似乎至少由几个局部阈下突触事件触发。我们得出结论，培养中的神经元网络可以产生自发同步活动，并作为分析大脑中网络活动规则的可行模型系统。
