Real time processing and synchronization in hybrid hippocampal microcircuits

Abstract

Objectives: Synchronization among neurons is thought to arise from the interplay between excitation and inhibition but the connectivity rules that contribute to synchronization are unknown.<br />Neuronal networks are extremely complex, not only because of the huge amount of cells involved but also because of the variety of different actions contributing to network activities. We studied this problem by investigating hippocampal microcircuits in CA1 using the multi channel patch clamp technique and real-time computing. Methods: The real-time system in combination with the patch clamp technique which is often referred to as dynamic clamp, allowed us to build hybrid neuronal networks containing both biological and artificial (modeled) cells. We were able to introduce the synaptic responses from other cells to patched neurons during network activity. By connecting a model interneuron with two pyramidal cells (PC), we were able to test the role of different connection rules in synchronizing pyramidal cell activity. Results: Our experiments demonstrated that eliminating the feedback from PCs to the interneuron produced the greatest level of synchronization.<br />We investigated several aspects of interneuron-PC-PC communication and studied the synchrony level of the two patched pyramidal cells by simulating different biological realistic hippocampal microcircuits.<br />Moreover we investigated the role of intrinsic membrane mechanisms contributing to synchronization. Application of the hyperpolarization-activated cyclic-nucleotide (HCN) cation channel current (Ih) blocker ZD7288 dramatically impaired PC synchronization and altered the connection pattern that produced the largest synchronization index. Conclusion: Our results shed light on how hippocampal microcircuits can synchronize and generate oscillatory activity. Additionally, we suggest how hippocampal neurons are connected and how these connections alter the way these circuits process information. We also demonstrate that changes in the conductance of HCN channels, by blocking them pharmacologically, can modulate hippocampal network synchronization.