Presynaptic inhibitory terminals are functionally abnormal in a rat model of posttraumatic epilepsy.
Partially isolated "undercut" neocortex with intact pial circulation is a well-established model of posttraumatic epileptogenesis. Results of previous experiments showed a decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal (Pyr) neurons of undercuts. We further examined possible functional abnormalities in GABAergic inhibition in rat epileptogenic neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. Compared with controls, IPSCs in Pyr neurons of injured slices showed increased threshold and decreased peak amplitude at threshold, decreased input/output slopes, increased failure rates, and a shift from paired pulse depression toward paired pulse facilitation (increased paired pulse ratio or PPR). Increasing [Ca(2+)](o) from 2 to 4 mM partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto FS cells also had an increased PPR and failures. Blockade of GABA(B) receptors did not affect the paired results. These findings suggest that there are functional alterations in GABAergic presynaptic terminals onto both Pyr and FS cells in this model of posttraumatic epileptogenesis.
Faria
Leonardo C
LC
Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, California 94305-5122, USA.
Prince
David A
DA
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D055724:Electrophysiological Phenomena; D004834:Epilepsy, Post-Traumatic / Q000209:etiology* / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D009044:Motor Cortex / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects; D013003:Somatosensory Cortex / Q000503:physiopathology
D018755:GABA Agonists; D018756:GABA Antagonists; D018080:Receptors, GABA-B; D002118:Calcium