Repeated hippocampal seizures lead to brain-wide reorganization of circuits and seizure propagation pathways.
Repeated hippocampal seizures lead to brain-wide reorganization of circuits and seizure propagation pathways.
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DOI：
10.1016/j.neuron.2021.10.010
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发表时间：
2022-01-19
期刊：
影响因子：
16.2
通讯作者：
Hyung, Jin
中科院分区：
文献类型：
--
作者：
Choy, ManKin;Dadgar-Kiani, Ehsan;Cron, Greg O.;Duffy, Ben A.;Schmid, Florian;Edelman, Bradley J.;Asaad, Mazen;Chan, Russell W.;Vahdat, Shahabeddin;Hyung, Jin
Repeated seizure activity can lead to long-term changes in seizure dynamics and behavior. However, resulting changes in brain-wide dynamics remain poorly understood. This is partly due to technical challenges in precise seizure control and in vivo whole brain mapping of circuit dynamics. Here, we developed an optogenetic kindling model through repeated stimulation of ventral hippocampal CAMKII neurons in adult rats. We then combined fMRI with electrophysiology to track brain-wide circuit dynamics resulting from non-afterdischarge (AD)-generating stimulations, and individual convulsive seizures. Kindling induced widespread increases in non-AD-generating stimulation response and ipsilateral functional connectivity, and elevated anxiety. Individual seizures in kindled animals showed more significant increases in brain-wide activity and bilateral functional connectivity. Onset time quantification provided evidence for kindled seizure propagation from the ipsilateral to contralateral hemisphere. Furthermore, a core of slow-migrating hippocampal activity was identified in both non-kindled and kindled seizures, revealing a novel mechanism of seizure sustainment and propagation. Choy et al. develop an optogenetic model for epilepsy through repeated stimulations of the hippocampus. Using whole brain functional imaging and electrical recordings, they uncover that kindling results in reorganization of brain-wide circuitry, engaging a larger brain-wide network upon stimulation, elevated anxiety, and a core of slow-migrating hippocampal activities.
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