Nonlinear frequency-dependent synchronization in the developing hippocampus.

Abstract

Synchronous population activity is present both in normal and pathological conditions such as epilepsy. In the immature hippocampus, synchronous bursting is an electrophysiological conspicuous event. These bursts, known as giant depolarizing potentials (GDPs), are generated by the synchronized activation of interneurons and pyramidal cells via GABAA, N-methyl-D-aspartate, and AMPA receptors. Nevertheless the mechanism leading to this synchronization is still controversial. We have investigated the conditions under which synchronization arises in developing hippocampal networks. By means of simultaneous intracellular recordings, we show that GDPs result from local cooperation of active cells within an integration period prior to their onset. During this time interval, an increase in the number of excitatory postsynaptic potentials (EPSPs) takes place building up full synchronization between cells. These EPSPs are correlated with individual action potentials simultaneously occurring in neighboring cells. We have used EPSP frequency as an indicator of the neuronal activity underlying GDP generation. By comparing EPSP frequency with the occurrence of synchronized GDPs between CA3 and the fascia dentata (FD), we found that GDPs are fired in an all-or-none manner, which is characterized by a specific threshold of EPSP frequency from which synchronous GDPs emerge. In FD, the EPSP frequency-threshold for GDP onset is 17 Hz. GDPs are triggered similarly in CA3 by appropriate periodic stimulation of mossy fibers. The frequency threshold for CA3 GDP onset is 12 Hz. These findings clarify the local mechanism of synchronization underlying bursting in the developing hippocampus, indicating that GDPs are fired when background levels of EPSPs or action potentials have built up full synchronization by firing at specific frequencies (>12 Hz). Our results also demonstrate that spontaneous EPSPs and action potentials are important for the initiation of synchronous bursts in the developing hippocampus.