Asymmetric dynamics of GABAergic system and paradoxical responses of GABAergic neurons in piriform seizures.

Autor: Tao Y; Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China., Zhao Y; Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China., Zhong W; Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China., Zhu H; Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China., Shao Z; Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China., Wu R; Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, China.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2024 Dec 10. Date of Electronic Publication: 2024 Dec 10.
DOI: 10.1111/epi.18202
Abstrakt: Objective: The piriform cortex (PC) plays a critical role in ictogenesis, where an excitation/inhibition imbalance contributes to epilepsy etiology. However, the epileptic dynamics of the gamma-aminobutyric acid (GABA) system and the precise role of GABAergic neurons within the PC in epilepsy remain unclear.
Methods: We combined Ca 2+ and GABA sensors to investigate the dynamics of Gad2-expressing neurons and GABA levels, and selectively manipulated GABAergic neurons in the PC through chemogenetic inhibition and caspase3-mediated apoptosis targeting Gad2 interneurons.
Results: GABAergic system dynamics in the PC were bidirectional and asymmetric, accompanied by PC optokindling-induced seizures, notably characterized by a robust response of Gad2 neurons but a rapid descent of GABA content during seizures. Chemogenetic inhibition of PC Gad2 neurons induced seizure-like behavior, with a discrepancy between the GABAergic neuron activities and GABA levels, signifying a transition from interictal to ictal states. Surprisingly, selective inhibition of Gad2 neurons in the PC produced paradoxical activation in a subset of Gad2 neurons. Moreover, the chronic deficiency of PC Gad2 neurons triggered spontaneous recurrent seizures.
Significance: Our findings uncover the dynamic interplay within PC inhibitory components and elaborate counteractive mechanisms in seizure regulation. These insights could inform future therapeutic strategies targeting GABAergic neurons to control epileptic activity.
(© 2024 International League Against Epilepsy.)
Databáze: MEDLINE
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