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(V)7/M-type K+ channel agonist retigabine to the apical dendrites. Severing the distal apical dendrites similar to 150 mu M 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.