Inter-ictal- and ictal-like epileptic discharges in the dendritic tree of neocortical pyramidal neurons.
Dendritic mechanisms have been implied to play a key role in the formation of epileptic discharges. However, presently only a handful of direct dendritic recordings have been reported during epileptic discharges. In this study, I performed simultaneous voltage recordings from the soma and apical dendrite of the same neuron combined with calcium-imaging measurements to investigate inter-ictal- and ictal-like epileptic discharges in dendrites of layer 5 pyramidal neurons. Neocortical brain slices treated with bicuculline (BCC) produced both isolated "inter-ictal" paroxysymal depolarization shift (PDS) responses and electrographic seizures. Concomitant voltage recordings from the soma and apical dendrite revealed that PDS responses developed in both the apical dendrites and soma. However, the two responses differed from one another. In apical dendrites, the PDS was significantly higher in amplitude and shorter in duration compared with the somatic PDS. The PDS response in dendrites had a peak amplitude of 68.9 +/- 2.2 (SD) mV, peak voltage value of 9.3 +/- 2.7 mV, and half-width of 203.8 +/- 38.4 ms. In contrast, the somatic PDS had a peak amplitude of 48.7 +/- 2.7 mV, peak voltage value of -11.9 +/- 3.1 mV, and half-width of 247.8 +/- 57.3 ms (P < 0.01, n = 18). In addition the apical dendritic PDS always preceded the somatic counterpart in all 18 neurons examined. Concomitant calcium-imaging measurements showed the PDS evoked large calcium influx into the entire dendritic tree including the apical tuft, basal, and oblique dendrites. The PDS evoked [Ca(2+)](i) were not uniform along the dendritic tree, being highest in the oblique dendrites (71.3 +/- 14.5 microM) and lowest at the distal tuft branches (9.3 +/- 0.7 microM). The PDS responses persisted after blockade of voltage-gated sodium channels by intracellular QX-314 but became narrower (by 69.6 +/- 9.7%) following intracellular administration of the voltage-gated calcium channel blocker D600. Electrographic seizures recorded in the soma and apical dendrites were composed of recurrent bursts. The initial bursts represented PDS responses. During the seizure the amplitude of bursts gradually attenuated and reached an average value of 26 +/- 13% of the initial ictal PDS burst. Double recordings during electrographic seizures revealed the initial one to four ictal bursts appeared first at the apical dendrite while later ictal bursts were always observed first at the soma. In conclusion, the results of this study show "inter-ictal" PDS responses originated in the apical dendritic tree, were partially mediated by voltage-gated calcium channels and spread throughout the dendritic tree including the fine tuft, basal, and oblique dendrites. During electrographic seizures the origin of epileptic bursts shifted from the apical dendritic tree to the soma-basal region.
Schiller
Yitzhak
Y
Department of Neurology, Rambam Medical Center, Haifa 31696, Israel. y.schiller@yahoo.com
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D019579:Neocortex / Q000503:physiopathology*; D009994:Osmolar Concentration; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats
D002118:Calcium