Electrophysiology of CA1 pyramidal neurons in an animal model of neuronal migration disorders: prenatal methylazoxymethanol treatment.
Prenatal methylazoxymethanol acetate (MAMac) injection disrupts cell migration in developing rats. We investigated the electrophysiological characteristics of hippocampal CA1 pyramidal neurons from young MAMac-treated animals (postnatal days 25-35). In vitro intracellular recordings from CA1 cells in MAMac-treated tissue revealed resting membrane potential (mean, -61.5 +/- 1.5 mV), action potential amplitude (mean, 69 +/- 3.1 mV), action potential duration (mean, 2.1 +/- 0.2 ms), input resistance (mean, 51.5 +/- 3.6 M omega) and time constant (mean, 33.2 +/- 1.2 ms) similar to those of CA1 cells from control tissue. However, MAMac-treated tissue could be distinguished as having a higher percentage of cells (62% vs. 10%) which fire a burst of action potentials in response to suprathreshold current injection. The synaptic responses of CA1 cells in MAMac-treated and control tissue were comparable. The CA1 field response to stimulation was also comparable at all stimulus intensities tested (50-1500 microA). Elevation of extracellular potassium concentration ([K+]o) from 3 mM to 6 mM resulted in epileptiform discharge activity in response to stratum radiatum stimulation in all MAMac-treated slices (10/10) but in only one-third of controls (3/9). Spontaneous epileptiform discharges were also observed in the majority (8/13) of MAMac-treated slices bathed in 6 mM KCl but in no controls. These data suggest that MAMac treatment during fetal development not only disrupts normal anatomical organization but also leads to alterations in electrophysiological features of the hippocampal CA1 pyramidal cell region. As such, the MAMac model may provide insights into early onset seizure syndromes associated with developmental abnormalities.
Baraban
S C
SC
Department of Neurological Surgery, University of Washington, Seattle 98195, USA.
Schwartzkroin
P A
PA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D008297:Male; D008746:Methylazoxymethanol Acetate; D008831:Microcephaly / Q000139:chemically induced / Q000503:physiopathology*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D008746:Methylazoxymethanol Acetate; D011189:Potassium Chloride