Spontaneous ictal-like discharges and sustained potential shifts in the developing rat neocortex

Academic Article

Abstract

  • Intra- and extracellular recording techniques were used to study epileptogenesis in in vitro slices of immature rat neocortex. Slices of sensorimotor cortex were prepared from animals 5-60 days old. Epileptiform activity was induced by bath application of 50 μM picrotoxin. Convulsant-induced paroxysmal activity was observed only rarely in the youngest age group (5-7 days) and consisted of orthodromically evoked bursts of low-amplitude isolated discharges. This activity was labile and could be evoked only at long interstimulus intervals (>10 s). Extracellular recordins in slices from 8- to 15-day-old rats showed spontaneous epileptiform activity consisting of 10- to 30-s paroxysms of repetitive spike discharges superimposed on a 3- to 5-mV negative steady potential. This steady potential declined slightly during the course of the prolonged discharge and returned quickly to base line following the last spike discharge. Laminar analysis of epileptiform activity in 8- to 15-day-old rats showed that the spike discharges were negative and superimposed on a positive slow wave in superficial cortical layers. At 100 μm below the pial surface, the slow potential reversed polarity and remained negative throughout the remainder of the cortex. Spike discharges reversed polarity 800 μm below the pial surface. In intracellular recordings from slices obtained from 9- to 14-day-old animals, each paroxysm began with a sharply rising membrane depolarization (paroxysmal depolarizing shift, or PDS). A second PDS occurred before the cells repolarized to their resting potential. A series of PDSs then followed, superimposed on a sustained membrane depolarization. This was associated with a 33% decrease in input resistance. Afterhyperpolarizations (AHPs) following termination of the depolarization were low in amplitude or absent. In the 16- to 30-day-old age group, extracellular recordings showed paroxysmal activity consisting of 3-10 initial spikes followed by a sustained, slow, negative-potential shift. This slow potential could be as great as 30 mV in amplitude and could last as long as 180 s. Paroxysmal events recurred spontaneously at intervals of 4-11 min. Spontaneous PDSs and slow, negative-potential shifts were not observed after 30 days of age, although PDSs could still be evoked by orthodromic stimulation. Intracellular recordings in the 16- to 30-day-old group revealed that each paroxysmal event consisted of an initial period of increased synaptic activity and cellular firing, following by a marked, long-lasting depolarization (LLD), culminating in an AHP. Input resistance was decreased during the initial burst of PDS-like activity and was virtually immeasurable during the peak of the LLD. Extracellular recordings showed that PDS activity conducted rapidly through the neocortex. LLDs traveled much slower, propagating at rates of 3-11 mm/min, indicative of a spreading depression type of phenomenon. Laminar analysis of LLDs indicated that their duration and amplitude varied as a function of depth in the cortex, but no reversal of the slow negativity was observed. These results show that the immature cortex is capable of generating synchronized epileptiform activity. The nature of the activity observed varies with the stage of development.
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    Author List

  • Hablitz JJ
  • Start Page

  • 1052
  • End Page

  • 1065
  • Volume

  • 58
  • Issue

  • 5