Developmental excitation of corticothalamic neurons by nicotinic acetylcholine receptors
Developmental excitation of corticothalamic neurons by nicotinic acetylcholine receptors
复制标题
DOI：
10.1523/jneurosci.2645-08.2008
复制
发表时间：
2008-08-27
影响因子：
5.3
通讯作者：
Lambe, Evelyn K.
中科院分区：
文献类型：
--
作者：
Kassam, Sameera M.;Herman, Patrick M.;Lambe, Evelyn K.
在这项研究中，我们展示了前额皮质第六层锥体神经元的强烈烟碱兴奋。该层包含皮质丘脑神经元，控制丘脑活动并在注意力方面发挥关键作用。我们的实验使用大鼠前额叶脑切片的全细胞记录来测试整个出生后发育过程中的烟碱兴奋。这些实验表明，第六层神经元在出生后第一个月（啮齿类动物皮质强烈发育的时期）具有峰值烟碱电流。我们证明这些电流是由突触后烟碱受体直接介导的，并且可以被α(4)β(2)*烟碱受体的竞争性拮抗剂抑制。为了记录已识别的皮质丘脑神经元，我们进行了立体定位手术来标记投射到内侧背侧丘脑的神经元。正如假设的那样，第六层中这些逆行标记神经元的记录显示出显着的烟碱电流。最后，我们检查了药物尼古丁对第六层神经元的影响，并探讨了辅助亚基 α(5) 在其受体中的潜在参与。尼古丁水平与吸烟者血液中的尼古丁水平相似，会在第 VI 层神经元中引发稳定的内向电流，但这种暴露会导致与乙酰胆碱引发的后续电流的 50% 类似的脱敏。 α(4)β(2)α(5) 受体的变构调节剂导致次最大烟碱电流增强 2.5 倍。该结果与VI层中相对罕见的α(5)烟碱亚基的表达一致。总之，我们表明第六层皮质丘脑神经元在发育过程中可以被烟碱受体的不寻常亚型强烈兴奋。
In this study, we show robust nicotinic excitation of pyramidal neurons in layer VI of prefrontal cortex. This layer contains the corticothalamic neurons, which gate thalamic activity and play a critical role in attention. Our experiments tested nicotinic excitation across postnatal development, using whole-cell recordings in prefrontal brain slices from rats. These experiments showed that layer VI neurons have peak nicotinic currents during the first postnatal month, a time period of intensive cortical development in rodents. Wedemonstrate that these currents are mediated directly by postsynaptic nicotinic receptors and can be suppressed by a competitive antagonist of alpha(4)beta(2)* nicotinic receptors. To record from identified corticothalamic neurons, we performed stereotaxic surgery to label the neurons projecting to medial dorsal thalamus. As hypothesized, recordings from these retrogradely labeled neurons in layer VI showed prominent nicotinic currents. Finally, we examined the effects of the drug nicotine on layer VI neurons and probed for the potential involvement of the accessory subunit, alpha(5), in their receptors. A level of nicotine similar to that found in the blood of smokers elicits a stable inward current in layer VI neurons, yet this exposure desensitizes similar to 50% of the subsequent current elicited by acetylcholine. An allosteric modulator of alpha(4)beta(2)alpha(5) receptors resulted in a 2.5-fold potentiation of submaximal nicotinic currents. This result is consistent with the expression of the relatively rare alpha(5) nicotinic subunit in layer VI. In summary, we show that layer VI corticothalamic neurons can be strongly excited during development by an unusual subtype of nicotinic receptor.