Mechanism of highly synchronized bilateral hippocampal activity

Abstract

In vivo studies of epileptiform discharges in the hippocampi of rodents have shown that bilateral seizure activity can sometimes be synchronized with very small delays (< 2 ms). This observed small time delay of epileptiform activity between the left and right CA3 regions is unexpected given the physiological propagation time across the hemispheres (> 6 ms). The goal of this study is to determine the mechanisms of this tight synchronization with in-vitro electrophysiology techniques and computer simulations. The hypothesis of a common source was first eliminated by using an in-vitro preparation containing both hippocampi with a functional ventral hippocampal commissure (VHC) and no other tissue. Next, the hypothesis that a noisy baseline could mask the underlying synchronous activity between the two hemispheres was ruled out by low noise in-vivo recordings and computer simulation of the noisy environment. Then we built a novel bilateral CA3 model to test the hypothesis that the phenomenon of very small left-to-right propagation delay of seizure activity is a product of epileptic cell network dynamics. We found that the commissural tract connectivity could decrease the delay between seizure events recorded from two sides while the activity propagated longitudinally along the CA3 layer thereby yielding delays much smaller than the propagation time between the two sides. The modeling results indicate that both recurrent and feedforward inhibition were required for shortening the bilateral propagation delay and depended critically on the length of the commissural fiber tract as well as the number of cells involved in seizure generation. These combined modeling/experimental studies indicate that it is possible to explain near perfect synchronization between the two hemispheres by taking into account the structure of the hippocampal network.

Identification of Pre-Spike Network in Patients with Mesial Temporal Lobe Epilepsy

“…Previously, it was thought that seizure and epileptiform discharges are initiated in one hippocampus and propagate to the contralateral hippocampus through the fornix. However, the short delay (20 ms) between activity in right and left hippocampi raises the possibility that the hippocampi are functionally synchronized ( 33 ). Studies of inter-hippocampal synchronization using intracranial EEG in animals and human beings have shown that normally, there is electrophysiological coherence between the hippocampi in the delta wave frequency range during wakefulness (0.5–2 Hz) ( 34 , 35 ) and rapid eye movement sleep ( 36 ).…”

Assessing functional connectivity across 3D tissue engineered axonal tracts using calcium fluorescence imaging

“…Pearson crosscorrelation and phase synchronization are used to infer non-directed synchronous patterns in the micro-TENN ROIs. Phase synchronization has previously been demonstrated both in vitro and in vivo, including from cortical and hippocampal local field potentials, and whole cell voltage clamp recordings of thalamic neurons [38], [39].…”

Microcircuits and their interactions in epilepsy: is the focus out of focus?

“…This finding suggests that chandelier cells may be specifically recruited by epileptic activity, and that by vetoing spike output via shut-down of pyramidal cell axons, may serve as a microcircuit emergency brake. Although the specific excitatory versus inhibitory effects of activating chandelier cells remain controversial 12,65–67 , their activation potentially represents another seizure choke point.…”