Mechanisms Behind the GABA-Mediated Field Potential in Hippocampus in the in vitro 4-aminopyridine Model of Epilepsy
Local field potentials (LFPs) mediated by GABAergic transmission have been recorded from resected human epileptic brain tissue, as confirmed by blockade of these events upon exposure to GABAergic transmission antagonists, and are generated through an unknown mechanism. To better understand the underlying causes of this abnormal synchronization of action potential firing of neurons it is therefore important to study the generation of GABAergic transmission-mediated LFPs. In the 4-aminopyridine (4-AP) in vitro model of epilepsy it has been previously established that one type of epileptiform LFP recorded in the hippocampus is generated by GABAergic transmission. Using a 60-channel perforated multi-electrode array (pMEA) I record LFPs and characterize the initiation and propagation of these events in mouse hippocampal slices. I found that LFPs initiated primarily in CA3. Most LFPs were of short duration and were restricted to CA3. I hypothesize that GABA-releasing interneurons in hippocampus are able to synchronize large groups of principal cells through depolarizing GABAergic transmission. Upon spike sorting of single unit activity I uncovered groups of neurons with interneuron characteristics, such as short action potential durations, that appeared to drive the propagation of the LFP from CA3 to DG. By utilizing juxtacellular and voltage clamp recordings and calcium imaging in combination with the pMEA, I also recorded low activity in granule cells during CA3-restricted LFPs and high activity when LFPs propagated to DG. This also suggests interneuron entrainment driving propagation into DG. Therefore, long duration LFPs that propagated to DG from CA3 appeared to recruit GABAergic transmission-mediated mechanisms that allowed for depolarization of most granule cells.
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