Altering cannabinoid signaling during development disrupts neuronal activity
Altering cannabinoid signaling during development disrupts neuronal activity
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DOI：
10.1073/pnas.0409641102
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发表时间：
2005-06-28
影响因子：
11.1
通讯作者：
Gozlan, H
中科院分区：
文献类型：
--
作者：
Bernard, C;Milh, M;Gozlan, H
在成人皮质组织中，GABA能抑制的募集阻止同步群体放电发展为癫痫活动。然而，在早期发育阶段，GABA是兴奋性的，因此无法发挥这一作用。在这里，我们报告说，逆行信号涉及内源性大麻素是负责突触传递的稳态控制和由此产生的网络模式在未成熟的海马。大麻素1型（CB1）受体的阻断导致癫痫放电，而CB1的过度激活降低了体内网络活动。因此，内源性大麻素信号能够将群体放电模式保持在狭窄的生理时间窗内，在一侧的癫痫和另一侧的稀疏活动之间保持平衡，这可能导致发育可塑性受损。在怀孕期间，在任何一个方向上扰乱这种微妙的平衡，例如，大麻作为CB1激动剂或作为抗肥胖药物销售的拮抗剂，即使在人类胚胎中也会对大脑成熟产生深远的影响。
In adult cortical tissue, recruitment of GABAergic inhibition prevents the progression of synchronous population discharges to epileptic activity. However, at early developmental stages, GABA is excitatory and thus unable to fulfill this role. Here,we report that retrograde signaling involving endocannabinoids is responsible for the homeostatic control of synaptic transmission and the resulting network patterns in the immature hippocampus. Blockade of cannabinoid type 1 (CB1) receptor led to epileptic discharges, whereas overactivation of CB1 reduced network activity in vivo. Endocannabinoid signaling thus is able to keep population discharge patterns within a narrow physiological time window, balancing between epilepsy on one side and sparse activity on the other, which may result in impaired developmental plasticity. Disturbing this delicate balance during pregnancy in either direction, e.g., with marijuana as a CB1 agonist or with an antagonist marketed as an antiobesity drug, can have profound consequences for brain maturation even in human embryos.