title: Selective activation of parvalbumin- or somatostatin-expressing interneurons triggers epileptic seizurelike activity in mouse medial entorhinal cortex.
abstract: GABAergic interneurons are thought to play a critical role in eliciting interictal spikes (IICs) and triggering ictal discharges in temporal lobe epilepsy, yet the contribution of different interneuronal subtypes to seizure initiation is still largely unknown. Here we took advantage of optogenetic techniques combined with patch-clamp and field recordings to selectively stimulate parvalbumin (PV)- or somatostatin (SOM)-positive interneurons expressing channelrhodopsin-2 (CHR-2) in layers II-III of adult mouse medial entorhinal cortical slices during extracellular perfusion with the proconvulsive compound 4-aminopyridine (4-AP, 100-200 μM). In control conditions, blue laser photostimulation selectively activated action potential firing in either PV or SOM interneurons and, in both cases, caused a robust GABAA-receptor-mediated inhibition in pyramidal cells (PCs). During perfusion with 4-AP, brief photostimuli (300 ms) activating either PV or SOM interneurons induced patterns of epileptiform activity that closely replicated spontaneously occurring IICs and tonic-clonic ictal discharges. Laser-induced synchronous firing in both interneuronal types elicited large compound GABAergic inhibitory postsynaptic currents (IPSCs) correlating with IICs and preictal spikes. In addition, spontaneous and laser-induced epileptic events were similarly initiated in concurrence with a large increase in extracellular potassium concentration. Finally, interneuron activation was unable to stop or significantly shorten the progression of seizurelike episodes. These results suggest that entorhinal PV and SOM interneurons are nearly equally effective in triggering interictal and ictal discharges that closely resemble human temporal lobe epileptic activity.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Latefa
authors.initials: L
authors.lastname: Yekhlef
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Breschi
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lagostena
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy stefano.taverna@iit.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Taverna
mesh_terms: D000200:Action Potentials; D000818:Animals; D018728:Entorhinal Cortex / Q000166:cytology / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D010320:Parvalbumins; D013004:Somatostatin
keywords: epilepsy; interneurons; optogenetics; parvalbumin; somatostatin