UMR5247 Institut des Biomolécules Max Mousseron - University of Montpellier-CNRS-ENSCM, Team 'Pharmacochemistry of Synaptic transmission and Neuroprotection', University of Montpellier-Sciences Faculty, Place E Bataillon, 34095, Montpellier Cedex 05, France.
Neurochem Res. 2019 Mar;44(3):609-616. doi: 10.1007/s11064-018-2476-0. Epub 2018 Jan 20.
Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the offspring. Cognitive/behavioral deficits are supported by changes in synaptic plasticity in different brain areas. We have reported previously that prenatal exposure to bacterial LPS could induce inhibition of hippocampal long-term potentiation (LTP) in the CA1 area of the juvenile/adult male offspring associated with spatial learning inabilities. Nevertheless, deficits in plasticity could be observed at earlier stages as shown by the early loss of long-term depression (LTD) in immature animals. Moreover, aberrant forms of plasticity were also evidenced such as the transient occurrence of LTP instead of LTD in 15-25 day-old animals. This switch from LTD to LTP seemed to involve the activation of metabotropic glutamate receptor subtype 1 and 5 (mGlu1/5). We have thus investigated here whether the long-term depression elicited by the direct activation of these receptors (mGlu-LTD) with a selective agonist was also disturbed after prenatal stress. We find that in prenatally stressed rats, mGlu1/5 stimulation elicits long-term potentiation (mGlu-LTP) independently of N-methyl-D-aspartate receptors. Both mGlu5 and mGlu1 receptors are involved in this switch of plasticity. Moreover, this mGlu-LTP is still observed at later developmental stages than previously reported, i.e. after 25 day-old. In addition, increasing synaptic GABA with tiagabine tends to inhibit mGlu-LTP occurrence. By contrast, long-term depression induced with the activation of CB1 cannabinoid receptor is unaffected by prenatal stress. Therefore, prenatal stress drastically alters mGlu1/5-associated plasticity throughout development. MGlu-mediated plasticity is an interesting parameter to probe the long-lasting deficits reported in this model.
母体免疫挑战已被证明会导致后代出现中度至重度的行为障碍。在不同的大脑区域，突触可塑性的变化支持认知/行为缺陷。我们之前曾报道过，产前暴露于细菌 LPS 可诱导幼年期/成年雄性后代 CA1 区海马长时程增强（LTP）抑制，与空间学习能力下降有关。然而，如在未成熟动物中早期失去长时程抑制（LTD）所表明的那样，在早期阶段就可以观察到可塑性的缺陷。此外，还出现了异常形式的可塑性，例如在 15-25 日龄的动物中短暂出现 LTP 而不是 LTD。这种从 LTD 到 LTP 的转变似乎涉及代谢型谷氨酸受体 1 和 5（mGlu1/5）亚型的激活。因此，我们在这里研究了直接激活这些受体（mGlu-LTD）的选择性激动剂是否也会在产前应激后引起长时程抑制的改变。我们发现，在产前应激的大鼠中，mGlu1/5 的刺激会引发长时程增强（mGlu-LTP），而不依赖于 N-甲基-D-天冬氨酸受体。mGlu5 和 mGlu1 受体都参与了这种可塑性的转变。此外，与之前报道的相比，这种 mGlu-LTP 发生在更晚的发育阶段，即在 25 日龄后。此外，用噻加宾增加突触 GABA 会抑制 mGlu-LTP 的发生。相反，用 CB1 大麻素受体的激活诱导的长时程抑制不受产前应激的影响。因此，产前应激在整个发育过程中强烈改变了 mGlu1/5 相关的可塑性。MGlu 介导的可塑性是一个有趣的参数，可以探测到该模型中报道的持久缺陷。
