title: Thalamic modulation of cingulate seizure activity via the regulation of gap junctions in mice thalamocingulate slice.
abstract: The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5-50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Wei-Pang
authors.initials: WP
authors.lastname: Chang
authors.forename: José Jiun-Shian
authors.initials: JJ
authors.lastname: Wu
authors.forename: Bai-Chuang
authors.initials: BC
authors.lastname: Shyu
mesh_terms: D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D004351:Drug Resistance; D017034:Epilepsy, Frontal Lobe / Q000473:pathology* / Q000503:physiopathology*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D015767:Mefloquine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D000442:Octanols / Q000494:pharmacology; D062211:Spatio-Temporal Analysis; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D013826:Theta Rhythm / Q000187:drug effects
chemical_list: D000442:Octanols; D002229:Carbenoxolone; D015767:Mefloquine