@entity302 are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most @entity410 involve two stages: an initial tonic phase, followed by a longer clonic phase that is characterized by rhythmic bouts of synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and network mechanisms underlying hippocampal ADs in an effort to understand how they maintain @entity410 activity. Using in vitro hippocampal slice models from @entity35 and @entity19 , we performed electrophysiological recordings from @entity4779 pyramidal neurons to monitor network activity and changes in GABAergic signaling during @entity302 . First, we show that the highest synchrony occurs during clonic ADs, consistent with the idea that specific circuit dynamics underlie this phase of the @entity302 . We then show that ADs require intact GABAergic synaptic transmission, which becomes excitatory as a result of a transient collapse in the @entity2865 (Cl(-)) reversal potential. The depolarizing effects of @entity1246 are strongest at the soma of pyramidal neurons, which implicates somatic-targeting interneurons in AD activity. To test this, we used optogenetic techniques to selectively control the activity of somatic-targeting @entity7053 -expressing (PV(+)) interneurons. Channelrhodopsin-2-mediated activation of PV(+) interneurons during the clonic phase generated excitatory GABAergic responses in pyramidal neurons, which were sufficient to elicit and entrain synchronous AD activity across the network. Finally, archaerhodopsin-mediated selective silencing of PV(+) interneurons reduced the occurrence of ADs during the clonic phase. Therefore, we propose that activity-dependent Cl(-) accumulation subverts the actions of PV(+) interneurons to perpetuate rather than terminate pathological network hyperexcitability during the clonic phase of @entity410 .

Excitatory effects of XXXX -expressing interneurons maintain @entity302 via synchronous afterdischarges.

@entity410 :: ('MESH:D012640', 'Disease') :: ['seizure', 'seizures'] @entity7053 :: ('25269(Tax:10116)', 'Gene') :: ['parvalbumin'] @entity1246 :: ('MESH:D005680', 'Chemical') :: ['GABA'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity4779 :: ('12350(Tax:10090)', 'Gene') :: ['CA3'] @entity302 :: ('MESH:D004827', 'Disease') :: ['Epileptic seizures', 'epileptiform activity'] @entity2865 :: ('CHEBI:17996', 'Chemical') :: ['chloride'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity7053 :: (25269(Tax:10116),Gene) :: ['parvalbumin']
