Recruitment of apical dendritic T-type Ca²⁺ 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 Ni²⁺ - and amiloride-sensitive T-type Ca²⁺ 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 Ni²⁺ to the apical dendrites, but not to the soma. It was also suppressed by applying either tetrodotoxin or the K_V7/M-type K⁺ channel agonist retigabine to the apical dendrites. Severing the distal apical dendrites ∼150 μm from the pyramidal layer also abolished this activity. Intradendritic recordings indicated that evoked bursts are associated with local Ni²⁺-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.