Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
J Neurosci. 2012 Aug 1;32(31):10484-93. doi: 10.1523/JNEUROSCI.5502-11.2012.
Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age can compromise the normal course of prefrontal development and lead to cognitive impairments in later life. Recently, we reported that nicotine exposure during adolescence results in a short-term increase and lasting reduction in synaptic mGluR2 levels in the rat mPFC, causing attention deficits during adulthood. It is unknown how changed synaptic mGluR2 levels after adolescent nicotine exposure affect the ability of mPFC synapses to undergo long-term synaptic plasticity. Here, we addressed this question. To model nicotine exposure, adolescent (P34-P43) or adult (P60-P69) rats were treated with nicotine injections three times per day for 10 d. We found that, both during acute activation of nicotinic receptors in the adolescent mPFC as well as immediately following nicotine treatment during adolescence, long-term plasticity in response to timed presynaptic and postsynaptic activity (tLTP) was strongly reduced. In contrast, in the mPFC of adult rats 5 weeks after they received nicotine treatment during adolescence, but not during adulthood, tLTP was increased. Short- and long-term adaptation of mPFC synaptic plasticity after adolescent nicotine exposure could be explained by changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, whereas activating mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure to nicotine during adolescence alters the rules for spike timing-dependent plasticity in prefrontal networks that may explain the observed deficits in cognitive performance in later life.
青春期是大脑发育的关键时期，在此期间，与认知功能相关的区域（如内侧前额叶皮质，mPFC）的成熟仍在继续。在此年龄段吸烟会损害前额叶发育的正常进程，并导致成年后认知障碍。最近，我们报道说，青春期暴露于尼古丁会导致大鼠 mPFC 中的突触 mGluR2 水平短期增加和持续减少，从而导致成年期注意力缺陷。目前尚不清楚青春期尼古丁暴露后改变的突触 mGluR2 水平如何影响 mPFC 突触发生长期突触可塑性的能力。在这里，我们解决了这个问题。为了模拟尼古丁暴露，青春期（P34-P43）或成年期（P60-P69）大鼠每天接受三次尼古丁注射，持续 10 天。我们发现，无论是在青春期 mPFC 中的烟碱型乙酰胆碱受体急性激活期间，还是在青春期期间进行尼古丁治疗后立即，针对定时的突触前和突触后活动的长期可塑性（tLTP）都明显减少。相比之下，在青春期接受尼古丁治疗后 5 周的成年大鼠的 mPFC 中，tLTP 增加，但在成年期没有增加。青春期尼古丁暴露后 mPFC 突触可塑性的短期和长期适应可以用改变的 mGluR2 信号来解释。阻断 mGluR2 增强了 tLTP，而激活 mGluR2 则降低了 tLTP。我们的研究结果表明，暴露于尼古丁会改变前额叶网络中与尖峰时间依赖性可塑性相关的规则的神经元机制，这可能解释了在以后的生活中观察到的认知表现缺陷。
