Dynamic electrical synapses rewire brain networks for persistent oscillations and epileptogenesis

• 成果类型: Article
• 署名作者: Yang, Ya-Chi; Wang, Guan- Hsun; Chou, Ping; Hsueh, Shu- Wei; Lai, Yi- Chen; Kuo, Chung-Chin
• 署名单位: Chang Gung University; Chang Gung University; Chang Gung Memorial Hospital; Chang Gung Memorial Hospital; Chang Gung Memorial Hospital; Chang Gung Memorial Hospital; National Taiwan University; National Taiwan University; National Taiwan University Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9834
• DOI: 10.1073/pnas.2313042121
• 发表日期: 2024-02-20
• 关键词: gabaergic interneurons; seizure susceptibility; antiepileptic drugs; zonula occludens-1; pyramidal cells; amygdala; excitability; inhibition; expression; excitation

摘要

One of the very fundamental attributes for telencephalic neural computation in mammals involves network activities oscillating beyond the initial trigger. The continuing and automated processing of transient inputs shall constitute the basis of cognition and intelligence but may lead to neuropsychiatric disorders such as epileptic seizures if carried so far as to engross part of or the whole telencephalic system. From a conventional view of the basic design of the telencephalic local circuitry, the GABAergic interneurons (INs) and glutamatergic pyramidal neurons (PNs) make negative feedback loops which would regulate the neural activities back to the original state. The drive for the most intriguing self- perpetuating telencephalic activities, then, has not been posed and characterized. We found activity- dependent deployment and delineated functional consequences of the electrical synapses directly linking INs and PNs in the amygdala, a prototypical telencephalic circuitry. These electrical synapses endow INs dual (a faster excitatory and a slower inhibitory) actions on PNs, providing a network- intrinsic excitatory drive that fuels the IN-PN interconnected circuitries and enables persistent oscillations with preservation of GABAergic negative feedback. Moreover, the entities of electrical synapses between INs and PNs are engaged in and disengaged from functioning in a highly dynamic way according to neural activities, which then determine the spatiotemporal scale of recruited oscillating networks. This study uncovers a special wide - range and context- dependent plasticity for wiring/rewiring of brain networks. Epileptogenesis or a wide spectrum of clinical disorders may ensue, however, from different scales of pathological extension of this unique form of telencephalic plasticity.