Recruitment of apical dendritic T‐type Ca 2 + channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis

A single episode of status epilepticus ( SE ) induced in rodents by the convulsant pilocarpine, produces, after a latent period of ≥ 2 weeks, a chronic epileptic condition. During the latent period of epileptogenesis, most CA1 pyramidal cells that normally fire in a regular pattern, acquire low‐threshold bursting behaviour, generating high‐frequency clusters of 3–5 spikes as their minimal response to depolarizing stimuli. Recruitment of a Ni 2+ ‐ and amiloride‐sensitive T‐type Ca 2+ current ( I CaT ), shown to be up‐regulated after SE , plays a critical role in burst generation in most cases. Several lines of evidence suggest that I CaT driving bursting is located in the apical dendrites. Thus, bursting was suppressed by focally applying Ni 2+ to the apical dendrites, but not to the soma. It was also suppressed by applying either tetrodotoxin or the K V 7/M‐type K + channel agonist retigabine to the apical dendrites. Severing the distal apical dendrites ∼150 μ m from the pyramidal layer also abolished this activity. Intradendritic recordings indicated that evoked bursts are associated with local Ni 2+ ‐sensitive slow spikes. Blocking persistent Na + current did not modify bursting in most cases. We conclude that SE ‐induced increase in I CaT density in the apical dendrites facilitates their depolarization by the backpropagating somatic spike. The I CaT ‐driven dendritic depolarization, in turn, spreads towards the soma, initiating another backpropagating spike, and so forth, thereby creating a spike burst. The early appearance and predominance of I CaT ‐driven low‐threshold bursting in CA1 pyramidal cells that experienced SE most probably contribute to the emergence of abnormal network discharges and may also play a role in the circuitry reorganization associated with epileptogenesis.