Determinants of spontaneous activity in networks of cultured hippocampus

Abstract

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.