TY - JOUR
T1 - Developmental characteristics of epileptiform activity in immature rat neocortex
T2 - A comparison of four in vitro seizure models
AU - Wong, Michael
AU - Yamada, Kelvin A.
N1 - Funding Information:
The authors thank Michael Province from the Division of Biostatistics at Washington University for assistance with the statistical analysis. This work was supported in part by NIH Neurological Sciences Academic Development Award 5K12NS0169004.
PY - 2001/6/29
Y1 - 2001/6/29
N2 - New-onset seizures and epilepsy have a relatively high incidence in infants and children. A leading hypothesis to explain an increased seizure susceptibility of the immature nervous system involves ontogenetic changes in different neurotransmitter systems, such as specific glutamate and GABA receptors. However, few studies have directly tested this hypothesis in a systematic fashion, especially in neocortical structures, where seizures in pediatric patients frequently arise. The present study investigated developmental changes in epileptiform activity in rat neocortical slices from four age groups (postnatal days P4-7, P13-16, P23-26, P41-47) due to four pharmacological conditions (4-aminopyridine, low magnesium, picrotoxin, CGP-35348) that differentially modulate glutamate and GABA systems. A characteristic age-dependence of the incidence of epileptiform activity was observed. In all pharmacological conditions, no epileptiform activity occurred in neocortical slices from P4-7 rats. Interictal discharges, ictal events, and spreading depression had a maximal incidence at P13-16 and decreased progressively in later age groups. 4-Aminopyridine, low magnesium, and picrotoxin induced all types of epileptiform activity with a similar age-dependent pattern, despite minor differences in quantitative characteristics of epileptiform activity between these three conditions. The GABAB antagonist, CGP-35348, did not elicit epileptiform activity in any age group, but could potentiate synaptic potentials. These findings establish that isolated neocortical tissue intrinsically displays ontogenetic changes in seizure susceptibility independent of systemic factors. The similar age-dependent patterns of epileptiform activity with multiple drugs support a concept of global developmental changes in excitability not specifically linked to any particular neurotransmitter system.
AB - New-onset seizures and epilepsy have a relatively high incidence in infants and children. A leading hypothesis to explain an increased seizure susceptibility of the immature nervous system involves ontogenetic changes in different neurotransmitter systems, such as specific glutamate and GABA receptors. However, few studies have directly tested this hypothesis in a systematic fashion, especially in neocortical structures, where seizures in pediatric patients frequently arise. The present study investigated developmental changes in epileptiform activity in rat neocortical slices from four age groups (postnatal days P4-7, P13-16, P23-26, P41-47) due to four pharmacological conditions (4-aminopyridine, low magnesium, picrotoxin, CGP-35348) that differentially modulate glutamate and GABA systems. A characteristic age-dependence of the incidence of epileptiform activity was observed. In all pharmacological conditions, no epileptiform activity occurred in neocortical slices from P4-7 rats. Interictal discharges, ictal events, and spreading depression had a maximal incidence at P13-16 and decreased progressively in later age groups. 4-Aminopyridine, low magnesium, and picrotoxin induced all types of epileptiform activity with a similar age-dependent pattern, despite minor differences in quantitative characteristics of epileptiform activity between these three conditions. The GABAB antagonist, CGP-35348, did not elicit epileptiform activity in any age group, but could potentiate synaptic potentials. These findings establish that isolated neocortical tissue intrinsically displays ontogenetic changes in seizure susceptibility independent of systemic factors. The similar age-dependent patterns of epileptiform activity with multiple drugs support a concept of global developmental changes in excitability not specifically linked to any particular neurotransmitter system.
KW - Development
KW - Epilepsy
KW - Neocortex
KW - Rat
KW - Seizure
KW - Synaptic transmission
UR - http://www.scopus.com/inward/record.url?scp=0035968044&partnerID=8YFLogxK
U2 - 10.1016/S0165-3806(01)00149-3
DO - 10.1016/S0165-3806(01)00149-3
M3 - Article
C2 - 11412897
AN - SCOPUS:0035968044
SN - 0165-3806
VL - 128
SP - 113
EP - 120
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 2
ER -