کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5630497 1580612 2018 15 صفحه PDF سفارش دهید دانلود کنید
عنوان انگلیسی مقاله ISI
Brief activation of GABAergic interneurons initiates the transition to ictal events through post-inhibitory rebound excitation
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Brief activation of GABAergic interneurons initiates the transition to ictal events through post-inhibitory rebound excitation
چکیده انگلیسی


- Brief GABA-mediated inhibition initiates ictal events in cortical 4-AP models.
- Post-inhibitory rebound excitation was observed at transition to ictal activity.
- Ictal events were observed to be an all-or-none phenomenon.
- Key findings were replicated in neocortical tissue resected from epilepsy patients.
- Inhibitory interneurons can play a critical role in the transition to ictal events.

Activation of γ-aminobutyric acid (GABAA) receptors have been associated with the onset of epileptiform events. To investigate if a causal relationship exists between GABAA receptor activation and ictal event onset, we activated inhibitory GABAergic networks in the superficial layer (2/3) of the somatosensory cortex during hyperexcitable conditions using optogenetic techniques in mice expressing channelrhodopsin-2 in all GABAergic interneurons. We found that a brief 30 ms light pulse reliably triggered either an interictal-like event (IIE) or ictal-like (“ictal”) event in the in vitro cortical 4-Aminopyridine (4-AP) slice model. The link between light pulse and epileptiform event onset was lost following blockade of GABAA receptors with bicuculline methiodide. Additionally, recording the chronological sequence of events following a light pulse in a variety of configurations (whole-cell, gramicidin-perforated patch, and multi-electrode array) demonstrated an initial hyperpolarization followed by post-inhibitory rebound spiking and a subsequent slow depolarization at the transition to epileptiform activity. Furthermore, the light-triggered ictal events were independent of the duration or intensity of the initiating light pulse, suggesting an underlying regenerative mechanism. Moreover, we demonstrated that brief GABAA receptor activation can initiate ictal events in the in vivo 4-AP mouse model, in another common in vitro model of epileptiform activity, and in neocortical tissue resected from epilepsy patients. Our findings reveal that the synchronous activation of GABAergic interneurons is a robust trigger for ictal event onset in hyperexcitable cortical networks.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 109, Part A, January 2018, Pages 102-116
نویسندگان
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