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Role of CA3 theta-modulated interneurons during the transition to spontaneous seizures
Journal article   Peer reviewed

Role of CA3 theta-modulated interneurons during the transition to spontaneous seizures

Suganya Karunakaran, Dane W Grasse and Karen A Moxon
Experimental neurology, v 283(Pt A), pp 341-352
Sep 2016
PMID: 27353968

Abstract

Action Potentials - physiology Animals CA3 Region, Hippocampal - pathology CA3 Region, Hippocampal - physiopathology Disease Models, Animal Epilepsy - chemically induced Epilepsy - drug therapy Epilepsy - pathology Interneurons - physiology Male Movement - physiology Muscarinic Agonists - toxicity Pilocarpine - toxicity Rats Rats, Long-Evans Statistics, Nonparametric Theta Rhythm - drug effects Theta Rhythm - physiology
Multiple studies have observed heterogeneous neuronal firing patterns as a local network transitions to spontaneous seizures. We demonstrated that separately examining interneurons and pyramidal cells during this transition in a rat model of temporal lobe epilepsy elucidates some of this heterogeneity. Recently, it was demonstrated that classifying cells into specific theta-related subtypes further clarified the heterogeneity. Moreover, changes in neuronal synchrony with the local field potential were identified and determined to be specific to interneurons during the transition to seizures. To extend our understanding of the chronic changes in epileptic networks, we examined field potentials and single neuron activity in the CA3 hippocampus of pilocarpine-treated rats during interictal periods and compared these to neuronal activity in healthy controls and during preictal periods. Neurons were classified into theta-subtypes based on changes in firing patterns during theta periods. As previously reported, we find a high probability of theta oscillations before seizure onset and a selective increase in theta-on interneuron firing rate immediately preceding seizure onset. However, we also find overall slower theta rhythm and a general decrease in subtype-specific firing during interictal periods compared to that in control animals. The decrease in subtype specific interneuron activity is accompanied by increases in synchrony. Exceptionally, theta-on interneurons, that selectively increase their firing rate at seizure onset, maintain similar firing rates and synchrony as controls during interictal period. These data suggest that increased synchrony during interictal periods may compensate for low firing rates creating instability during theta that is prone to seizure initiation via a transition to hyper-synchronous activation of theta-on interneurons.

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