The Septum–Hippocampal Cholinergic Circuit: A Novel Pathway for Seizure Control
The Septum–Hippocampal Cholinergic Circuit: A Novel Pathway for Seizure Control
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DOI：
10.1016/j.biopsych.2020.02.003
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发表时间：
2020-05
影响因子：
10.6
通讯作者：
J. Bao;Yan Jin;Yue-Peng Jiang;R. Khanna;Jie Yu
中科院分区：
文献类型：
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作者：
J. Bao;Yan Jin;Yue-Peng Jiang;R. Khanna;Jie Yu
颞叶癫痫(TLE)是一种常见的成人1号局灶性癫痫，通常起源于海马体，是一种常见的耐药形式。鉴于神经元兴奋和抑制之间的失衡在癫痫发作中的关键作用，大多数3种临床抗癫痫药物作用于离子通道或调节4个兴奋性谷氨酸能和/或抑制性GABA能神经元的突触功能(1)。然而，超过5-70%的TLE患者不能用现有的6种抗癫痫药物达到足够的控制。最近，在《生物精神病学》杂志上，Ying和7位同事发现了内侧隔(MS)-海马区8号胆碱能回路在TLE癫痫发作中的具体作用，并对目前的9号癫痫网络理论提出了另一种观点(2)。他们发现，患有海马区硬化症的TLE患者表现出MS体积和MS与海马区之间的神经纤维连接减少。这一发现并不完全出乎意料，因为TLE患者的脑核萎缩12和异常纤维连接之前已经在几个成像研究中报道过13个，包括下丘脑丘脑和14个内嗅觉皮质通路(3)。有趣的是，据报道，在没有海马硬化的TLE患者中，MS体积增加了15个(4)，而在有海马硬化症的TLE患者中，MS体积减少了16个，这一发现反映了Ms17在TLE患者中的不同作用。它还指出，MS中胆碱能神经元对TLE调制的作用可能发生了18个变化。这些报告共同提供了令人信服的证据，进一步探讨了MS 20在TLE的发生和随后的病理变化中的潜在作用。MS是一个富含胆碱能、GABA能和谷氨酸能神经元的核团。22
Temporal lobe epilepsy (TLE) is a common and drug-resistant form of adult focal 1 epilepsy, typically originating from the hippocampus. Given the critical role of the 2 imbalance between neuronal excitation and inhibition in epileptic seizures, most 3 clinical antiepileptic drugs work on ion channels or regulate synaptic function of 4 excitatory glutamatergic and/or inhibitory GABAergic neurons (1). However, more 5 than 70% of TLE patients are not able to achieve adequate control with current 6 antiepileptic drugs. Recently, in the issue of Biological Psychiatry, Ying and 7 colleagues identified the specific role of the medial septum (MS)-hippocampus 8 cholinergic circuit in seizures of TLE, and provided an alternative view of current 9 epileptic network theory (2). They found that TLE patients with hippocampal 10 sclerosis showed a decrease of the volume of MS and neuronal fiber connectivity 11 between the MS and hippocampus. This finding is not totally unexpected as atrophy 12 of brain nuclei and dysmorphic fiber connectivity in TLE patients has been previously 13 reported in several imaging studies, including those on the subiculum, thalamus, and 14 the entorhinal cortex pathways (3). It is intriguing that MS volume was reported to be 15 increased in TLE patients without hippocampal sclerosis (4) but decreased in TLE 16 patients with hippocampal sclerosis, a finding that reflects differential roles of the MS 17 in TLE patients with or without hippocampal sclerosis. It also points to possible 18 changes in the effects of cholinergic neurons in MS on modulation of TLE. Together 19 these reports provide compelling evidence to further pursue the potential role of MS 20 in development of TLE and examination of ensuing pathological changes. 21 The MS is a nucleus rich in cholinergic, GABAergic and glutamatergic neurons. 22