Short-interval amygdala kindling in neonatal rats

Abstract

The kindling paradigm provides a powerful tool for studying the generation, propagation and generalization of seizures. Such reproducible quantitative paradigms are a prerequisite for the experimental study of epilepsy in the developing brain. Kindling has been extensively utilized as a model of limbic seizures in the adult rat; amygdala short-interval kindling has been studied in > or = 15-day-old rats. We applied the short-interval kindling method, i.e., stimulation at every 15 min, to 7-12-day-old rats. Stage-5 behavioral seizures were achieved even in 7-day-old rats; however, the progression of behavioral kindling differed somewhat from that of older rats. Correlation of electrographic discharges and behavioral phenomena was inversely related to age. Reliable progressive amygdala discharges were difficult to assess in most < or = 10-day-old rats. Spontaneous seizures occurred relatively frequently in younger age groups. The amygdala short-interval kindling paradigm is reproducibly and reliably applicable to rats during the 2nd postnatal week. The presence of progressive focal to bilateral-generalized seizures suggests a significant functional maturity of the amygdala-limbic circuitry at this age.

Fig. 1

AD in 7–12-day-old rats subjected to short-interval stimulation. A: 7-day-old rat, subsequent to fifth stimulation. B: 9-day-old rat, fifth stimulation. C: 10-day-old rat, 19th stimulation. D: 12-day-old rat, 17th stimulation. Horizontal bar, 1 s; vertical bar, 10 μV in A, 20 μV in B and C, and 40 μV in D.

Fig. 2

Comparison of kindling rates in 7–8- and 12-day-old rats. Individual rats are plotted, showing number of stimulations for each behavioral stage. Inter-individual variability and kindling rate are higher in younger rats. Note different y axes (stimulation number).

Fig. 3

Correlation of AD duration and stimulation number in 9- and 12-day-old rats. See text for details of kindling paradigm.