The endocannabinoid system controls key epileptogenic circuits in the hippocampus
The endocannabinoid system controls key epileptogenic circuits in the hippocampus
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DOI：
10.1016/j.neuron.2006.07.006
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发表时间：
2006-08-17
期刊：
影响因子：
16.2
通讯作者：
Lutz, Beat
中科院分区：
文献类型：
--
作者：
Monory, Krisztina;Massa, Federico;Lutz, Beat
神经元活动的平衡控制在维持神经元回路的功能和活力中是中心的。内源性大麻素系统严格控制神经元的兴奋性。在这里，我们表明，内源性大麻素直接靶向海马神经元，以提供对小鼠急性癫痫样发作的保护。功能性CB1大麻素受体存在于海马结构的谷氨酸能末端，与囊泡谷氨酸转运体1（VGluT1）共定位。皮质海马能神经元或前脑GABA能神经元中CB1基因的条件性缺失，以及海马中CB1基因的病毒诱导的缺失，证明海马能神经元中CB1受体的存在对于提供针对红藻氨酸（KA）诱导的癫痫发作的实质性内源性保护是必要且充分的。直接内源性大麻素介导的控制海马神经递质的神经传递可能构成一个有前途的治疗靶点，用于治疗与过度兴奋性神经元活动相关的疾病。
Balanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate that the presence of CB1 receptors in glutamatergic hippocampal neurons is both necessary and sufficient to provide substantial endogenous protection against kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity.