Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
Neurobiol Learn Mem. 2021 May;181:107445. doi: 10.1016/j.nlm.2021.107445. Epub 2021 Apr 22.
In rodent models of smoking during pregnancy, early postnatal nicotine exposure results in impaired hippocampus-dependent memory, but the underlying mechanism remains elusive. Given that hippocampal cholinergic systems modulate memory and rapid development of hippocampal cholinergic systems occurs during nicotine exposure, here we investigated its impacts on cholinergic function. Both nicotinic and muscarinic activation produce transient or long-lasting depression of excitatory synaptic transmission in the hippocampal CA1 region. We found that postnatal nicotine exposure impairs both the induction and nicotinic modulation of NMDAR-dependent long-term depression (LTD). Activation of muscarinic receptors decreases excitatory synaptic transmission and CA1 network activity in both wild-type and α2 knockout mice. These muscarinic effects are still observed in nicotine-exposed mice. M1 muscarinic receptor activity is required for mGluR-dependent LTD. Early postnatal nicotine exposure has no effect on mGluR-dependent LTD induction, suggesting that it has no effect on the function of m1 muscarinic receptors involved in this form of LTD. Our results demonstrate that early postnatal nicotine exposure has more pronounced effects on nicotinic function than muscarinic function in the hippocampal CA1 region. Thus, impaired hippocampus-dependent memory may arise from the developmental disruption of nicotinic cholinergic systems in the hippocampal CA1 region.
在孕期吸烟的啮齿动物模型中，早期产后尼古丁暴露会导致海马体依赖的记忆受损，但潜在的机制仍不清楚。鉴于海马胆碱能系统调节记忆，并且海马胆碱能系统在尼古丁暴露期间迅速发育，我们在这里研究了它对胆碱能功能的影响。烟碱型和毒蕈碱型受体的激活都会导致海马 CA1 区兴奋性突触传递产生短暂或持久的抑制。我们发现，产后尼古丁暴露会损害 NMDAR 依赖性长时程抑制（LTD）的诱导和烟碱调节。毒蕈碱受体的激活会降低野生型和α2 敲除小鼠中的兴奋性突触传递和 CA1 网络活动。在尼古丁暴露的小鼠中仍观察到这些毒蕈碱作用。M1 毒蕈碱受体活性是 mGluR 依赖性 LTD 所必需的。早期产后尼古丁暴露对 mGluR 依赖性 LTD 诱导没有影响，表明它对参与这种 LTD 形式的 m1 毒蕈碱受体的功能没有影响。我们的结果表明，早期产后尼古丁暴露对海马 CA1 区的烟碱功能的影响比毒蕈碱功能更为显著。因此，海马体依赖的记忆受损可能源于海马体 CA1 区烟碱胆碱能系统的发育障碍。
