Neonatal NMDA blockade alters the LTP, LTD and cognitive functions in male and female Wistar rats
Neonatal NMDA blockade alters the LTP, LTD and cognitive functions in male and female Wistar rats
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DOI：
10.1016/j.neuropharm.2021.108896
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发表时间：
2022-03-01
影响因子：
4.7
通讯作者：
Amani, Mohammad
中科院分区：
文献类型：
--
作者：
Golitabari, Nastaran;Mohammadian, Forouzan;Amani, Mohammad
有令人信服的证据表明，苯环利定(PCP)对新生儿NMDA受体的阻断与成年后的认知障碍有关，但对早期PCP治疗对晚年突触功能的影响知之甚少。在这里，我们试图确定早期接触五氯苯酚是否会改变成年大鼠海马CA1区神经元的电生理功能。为此，雄性和雌性Wistar大鼠在出生后第7天、第9天和第11天分别给予生理盐水或PCP(10 mg/kg)，然后在成年时分别进行行为和电生理测试。新生儿PCP治疗不改变基本的突触传递，仅对频率跟随(FF)能力有轻微影响，但显着降低Schaffer侧支(SC)-CA1通路的双脉冲促进(PPF)。我们发现，PCP处理显著减弱了成年大鼠CA1神经元的长时程增强(LTP)和长时程抑制(LTD)，并伴随着复杂反应谱的明显改变。电生理学数据在雄性和雌性大鼠中具有可比性，并且可靠地与这些动物的空间参考和工作记忆受损有关。总之，这项研究表明，在生命早期阻断NMDA受体降低了成年后CA1神经元的短期和长期突触可塑性和复杂的反应谱。
There is compelling evidence that neonatal blockade of NMDA receptors by phencyclidine (PCP) is associated with cognitive impairment in adulthood but little is known about the effects of early life PCP treatment on synaptic function later in life. Here, we sought to determine whether early life exposure to PCP alters the electrophysiologic function of hippocampal CA1 neurons in adult rats. To this end, male and female Wistar rats received either saline or PCP (10 mg/kg) on postnatal days (PND) 7, 9, and 11, and then underwent separate behavioral and electrophysiology tests in adulthood. Neonatal PCP treatment did not alter basic synaptic transmission and had only a modest effect on frequency following (FF) capacity but significantly decreased the paired-pulse facilitation (PPF) in the Schaffer collateral (SC)-CA1 pathway. We found that PCP treatment significantly attenuated the long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons accompanied by pronounced alteration in complex response profile in adult rats. The electrophysiology data were comparable in male and female rats and reliably associated with impaired spatial reference and working memories in these animals. Overall, this study suggests that blockade of NMDA receptors during early life de-teriorates the short-term and long-term synaptic plasticity and complex response profile of CA1 neurons in adulthood.