Abnormalities in GABAergic synaptic transmission of intralaminar thalamic neurons in a genetic rat model of absence epilepsy.
Synaptic activity mediated via GABA receptors in thalamic circuits is critically involved in the generation of hypersynchrony associated with absence epilepsy. Neurons of "unspecific" intralaminar thalamic nuclei display characteristic burst patterns during seizure activity, although their synaptic properties remain largely unknown. Here, we used in vitro patch-clamp techniques in neurons of the paracentral (PC) thalamic nucleus, derived from a genetic model of absence epilepsy (WAG-Rij) and a non-epileptic control strain (ACI) to elucidate intrinsic and synaptic properties. PC neurons displayed voltage-dependent low threshold spike bursts or tonic spike firing, typical of thalamic neurons. These parameters, and electrotonic properties, were similar in PC neurons of the two strains. Analyses of miniature inhibitory post synaptic currents (mIPSCs) mediated via GABA(A) receptors revealed no difference in decay time constant and inter-event interval between strains, but a significantly larger amplitude and higher single channel conductance (as assessed by non-stationary variance analysis) in WAG-Rij compared to ACI. By comparison, thalamocortical neurons from the ventrobasal complex of the thalamus showed no difference in mIPSC kinetics and unitary conductance between the two rat strains. In view of the critical role of GABAergic inhibition for synchronous activity in thalamocortical circuits, it is concluded that the increase in unitary conductance of IPSCs in PC neurons contributes to hypersynchrony characterizing seizure activity.
Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Johannes
J
Brockhaus
Hans-Christian
HC
Pape
D000818:Animals; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D020646:Intralaminar Thalamic Nuclei / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid