title: Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic-anterior cingulate slice.
abstract: OBJECTIVE
  Seizure-like activities generated in anterior cingulate cortex (ACC) are usually classified as simple partial and are associated with changes in autonomic function, motivation, and thought. Previous studies have shown that thalamic inputs can modulate ACC seizure, but the exact mechanisms have not been studied thoroughly. Therefore, we investigated the role of thalamic inputs in modulating ACC seizure-like activities. In addition, seizure onset and propagation are difficult to determine in vivo in ACC. We studied the spatiotemporal changes in epileptiform activity in this cortex in a thalamic-ACC slice to clearly determine seizure onset.
  
  
  METHODS
  We used multielectrode array (MEA) recording and calcium imaging to investigate the modulatory effect of thalamic inputs in a thalamic-ACC slice preparation.
  
  
  RESULTS
  Seizure-like activities induced with 4-aminopyridine (4-AP; 250 μm) and bicuculline (5-50 μm) in ACC were attenuated by glutamate receptor antagonists, and the degree of disinhibition varied with the dose of bicuculline. Seizure-like activities were decreased with 1 Hz thalamic stimulation, whereas corpus callosum stimulation could increase ictal discharges. Amplitude and duration of cingulate seizure-like activities were augmented after removing thalamic inputs, and this effect was not observed with those induced with elevated bicuculline (50 μm). Seizure-like activities were initiated in layers II/III and, after thalamic lesions, they occurred mainly in layers V/VI. Two-dimensional current-source density analyses revealed sink signals more frequently in layers V/VI after thalamic lesions, indicating that these layers produce larger excitatory synchronization. Calcium transients were synchronized after thalamic lesions suggesting that ACC seizure-like activities are subjected to desynchronizing modulation by thalamic inputs. Therefore, ACC seizure-like activities are subject to desynchronizing modulation from medial thalamic inputs to deep layer pyramidal neurons.
  
  
  CONCLUSIONS
  Cingulate seizure-like activities were modulated significantly by thalamic inputs. Repeated stimulation of the thalamus efficiently inhibited epileptiform activity, demonstrating that the desynchronization was pathway-specific. The clinical implications of deep thalamic stimulation in the modulation of cingulate epileptic activity require further investigation.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wei-Pang
authors.initials: WP
authors.lastname: Chang
authors.forename: Jiun-Shian
authors.initials: JS
authors.lastname: Wu
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Lee
authors.forename: Brent A
authors.initials: BA
authors.lastname: Vogt
authors.forename: Bai-Chuang
authors.initials: BC
authors.lastname: Shyu
mesh_terms: D015761:4-Aminopyridine / Q000633:toxicity; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000633:toxicity; D001683:Biological Clocks / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003337:Corpus Callosum / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004566:Electrodes; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D013788:Thalamus / Q000502:physiology*
chemical_list: D009118:Muscimol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015761:4-Aminopyridine; D002118:Calcium; D001640:Bicuculline