Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Brain. 2022 Jul 29;145(7):2347-2360. doi: 10.1093/brain/awac073.
Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyperexcitation, then propagate more broadly once inhibitory restraint in the surround is overcome.
癫痫发作被认为是由于兴奋和抑制性神经元活动失衡引起的。虽然大多数经典研究表明过度兴奋的神经活动起主要作用，但一些最新的发现对这一观点提出了挑战，反而认为抑制性神经元的过度活动会引发癫痫发作。我们使用核定位钙传感器对斑马鱼癫痫模型进行了双光子成像，研究了整个大脑中兴奋性和抑制性神经元活动的失衡问题。我们发现，癫痫发作总是从中脑的特定区域开始，然后再传播到其他脑区。与传播区相比，起始区兴奋性神经元的数量更多，也更容易被招募。这些发现支持了一种机制性的观点，即癫痫发作起始于一个过度兴奋的区域，然后在周围抑制作用被克服后更广泛地传播。
