Revealing single-neuron and network-activity interaction by combining high-density microelectrode array and optogenetics.

The synchronous activity of neuronal networks is considered crucial for brain function. However, the interaction between single-neuron activity and network-wide activity remains poorly understood. This study explored this interaction within cultured networks of rat cortical neurons. Employing a combination of high-density microelectrode array recording and optogenetic stimulation, we established an experimental setup enabling simultaneous recording and stimulation at a precise single-neuron level that can be scaled to the level of the whole network. Leveraging our system, we identified a network burst-dependent response change in single neurons, providing a possible mechanism for the network-burst-dependent loss of information within the network and consequent cognitive impairment during epileptic seizures. Additionally, we directly recorded a leader neuron initiating a spontaneous network burst and characterized its firing properties, indicating that the bursting activity of hub neurons in the brain can initiate network-wide activity. Our study offers valuable insights into brain networks characterized by a combination of bottom-up self-organization and top-down regulation.