title: Altered spontaneous synaptic inhibition in an animal model of cerebral heterotopias.
abstract: We have investigated spontaneous synaptic transmission in hippocampal nodular heterotopias in rats exposed to methylazoxymethanol (MAM) in utero. Pregnant Wistar rats were injected with MAM at E16. Acute hippocampal slices were prepared from the rat pups P14 to P40. Whole-cell voltage-clamp recordings were made from visually identified neurons using IR-DIC video microscopy. Synaptic events were recorded from either heterotopic neurons in the CA1 region or "slice-matched" normotopic CA1 pyramidal neurons. Both the spontaneous inhibitory (sIPSC) and excitatory synaptic transmission (sEPSC) to the same neurons were recorded. We found a profound reduction in the frequency of sIPSCs in the heterotopic neurons vs. normotopic neurons. No significant differences in the frequency of sEPSCs were found. We also found a profound reduction in the frequency of spontaneous IPSCs in normotopic neurons following application of the GABA reuptake blocker, NO-711, even in the presence of a GABA(B) receptor antagonist (CGP 55845). Preferentially blocking extrasynaptic GABA(A) receptors caused an increased frequency of sIPSCs in the heterotopic neurons. Our data suggest that there is a predominant change in inhibitory synaptic transmission, as measured by changes in sIPSCs, with no change in excitatory synaptic transmission to heterotopic neurons in hippocampus of rats exposed to MAM in utero. We suggest that this change is caused by an increase in the extracellular concentration of GABA but is not mediated via activation of presynaptic GABA(B) receptors. Rather, we propose that the increased extracellular GABA concentration in the heterotopias dampens the activity in inhibitory neurons via activation of extrasynaptic GABA(A) receptors.
authors.affiliation: Epilepsy Research Group, Section of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, SE 413 45 Göteborg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.forename: Catarina
authors.initials: C
authors.lastname: Lindquist
authors.forename: Kristina
authors.initials: K
authors.lastname: Malmgren
authors.forename: Fredrik
authors.initials: F
authors.lastname: Asztely
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D054091:Periventricular Nodular Heterotopia / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D055366:Synaptic Potentials / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid