Selective inhibition of excitatory synaptic transmission alters the emergent bursting dynamics of in vitro neural networks

Neurons in vitro connect to each other and form neural networks that display emergent electrophysiological activity. This activity begins as spontaneous uncorrelated firing in the early phase of development, and as functional excitatory and inhibitory synapses mature, this activity typically emerges as spontaneous network bursts. Network bursts are events of coordinated global activation among many neurons interspersed with periods of silencing and are important for synaptic plasticity, neural information processing, and network computation. While bursting is the consequence of balanced excitatory-inhibitory (E/I) interactions, the functional mechanisms underlying their evolution from physiological to potentially pathophysiological states are still poorly understood. This is partly because we have limited knowledge of and access to the synaptic connections themselves. In this study, we used selective chemogenetic inhibition to target and disrupt excitatory synaptic transmission in in vitro neural networks to study functional response and recovery of spontaneous network bursts over time. We found that inhibition resulted in neural networks subsequently exhibiting high frequency network bursts with high number of spikes per bursts, and with up to 98% of all spikes being in network bursts. Our results imply that the disruption in excitatory synaptic transmission during early network development likely affected inhibitory synaptic maturity which resulted in an overall decrease in network inhibition at later stages. These findings give evidence to the importance of E/I balance in maintaining physiological bursting patterns in neural networks.