Amakhin Dmitry V, Ergina Julia L, Chizhov Anton V, Zaitsev Aleksey V
Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences Saint Petersburg, Russia.
Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesSaint Petersburg, Russia; Computational Physics Laboratory, Division of Plasma Physics, Atomic Physics and Astrophysics, Ioffe InstituteSaint Petersburg, Russia.
Front Cell Neurosci. 2016 Oct 13;10:233. doi: 10.3389/fncel.2016.00233. eCollection 2016.
In epilepsy, the balance of excitation and inhibition underlying the basis of neural network activity shifts, resulting in neuronal network hyperexcitability and recurrent seizure-associated discharges. Mechanisms involved in ictal and interictal events are not fully understood, in particular, because of controversial data regarding the dynamics of excitatory and inhibitory synaptic conductances. In the present study, we estimated AMPAR-, NMDAR-, and GABA R-mediated conductances during two distinct types of interictal discharge (IID) in pyramidal neurons of rat entorhinal cortex in cortico-hippocampal slices. Repetitively emerging seizure-like events and IIDs were recorded in high extracellular potassium, 4-aminopyridine, and reduced magnesium-containing solution. An original procedure for estimating synaptic conductance during IIDs was based on the differences among the current-voltage characteristics of the synaptic components. The synaptic conductance dynamics obtained revealed that the first type of IID is determined by activity of GABA R channels with depolarized reversal potential. The second type of IID is determined by the interplay between excitation and inhibition, with early AMPAR and prolonged depolarized GABA R and NMDAR-mediated components. The study then validated the contribution of these components to IIDs by intracellular pharmacological isolation. These data provide new insights into the mechanisms of seizures generation, development, and cessation.
在癫痫中，神经网络活动基础的兴奋与抑制平衡发生改变，导致神经网络兴奋性过高以及与癫痫发作相关的反复放电。发作期和发作间期事件所涉及的机制尚未完全明确，尤其是关于兴奋性和抑制性突触电导动力学存在争议性数据。在本研究中，我们在皮质-海马脑片中，对大鼠内嗅皮层锥体细胞两种不同类型的发作间期放电（IID）期间，由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）、N-甲基-D-天冬氨酸受体（NMDAR）和γ-氨基丁酸受体（GABA R）介导的电导进行了评估。在高细胞外钾、4-氨基吡啶以及含镁量降低的溶液中记录到反复出现的癫痫样事件和IID。一种用于评估IID期间突触电导的原始方法基于突触成分电流-电压特性之间的差异。所获得的突触电导动力学表明，第一种类型的IID由具有去极化反转电位的GABA R通道活性决定。第二种类型的IID由兴奋与抑制之间的相互作用决定，早期有AMPAR以及持续的去极化GABA R和NMDAR介导的成分。然后该研究通过细胞内药理学分离验证了这些成分对IID的作用。这些数据为癫痫发作、发展和停止的机制提供了新的见解。
