Gioanni Y, Rougeot C, Clarke P B, Lepousé C, Thierry A M, Vidal C
INSERM U114, Collège de France, Paris, France.
Eur J Neurosci. 1999 Jan;11(1):18-30. doi: 10.1046/j.1460-9568.1999.00403.x.
The modulatory influence of nicotinic acetylcholine receptor (nAChRs) on thalamocortical transmission was characterized in the prelimbic area (PrL) of the rat prefrontal cortex. In the first experiment, rats received a unilateral excitotoxic lesion centred on the mediodorsal thalamic nucleus (MD), and were sacrificed 1 week later. The lesion resulted in a 40% reduction of 3H-nicotine autoradiographic labelling in the ipsilateral prefrontal cortex, particularly in areas that are innervated by the MD. Electrophysiological experiments were subsequently performed in non-lesioned anaesthetized animals, in order to study modulation of short- and long-latency responses of PrL neurons evoked by electrical stimulation of the MD. The short-latency responses result from activation of the MD-PrL pathway and are mediated via AMPA-type glutamatergic receptors, whereas the long-latency responses reflect activation of the recurrent collaterals of cortical pyramidal neurons, Iontophoretic application of nicotinic agonists (nicotine, DMPP) facilitated both types of response. Local application of the nAChR antagonists dihydro-beta-erythroidine, mecamylamine and methyllycaconitine, prevented both kinds of facilitation. Finally, intracerebral microdialysis experiments were performed in order to test for nicotinic modulation of extracellular glutamate concentrations in the PrL. Direct application of nicotine via the dialysis probe increased glutamate levels in a dose-dependent manner. This effect was blocked by local perfusion of dihydro-beta-erythroidine. These findings therefore provide anatomical and functional evidence for nAChR-mediated modulation of thalamocortical input to the prefrontal cortex. Such a mechanism may be relevant to the cognitive effects of nicotine and nicotinic antagonists.
在大鼠前额叶皮质的前边缘区（PrL）研究了烟碱型乙酰胆碱受体（nAChRs）对丘脑皮质投射的调节作用。在第一个实验中，大鼠接受以背内侧丘脑核（MD）为中心的单侧兴奋性毒性损伤，并在1周后处死。该损伤导致同侧前额叶皮质中3H-尼古丁放射自显影标记减少40%，特别是在接受MD神经支配的区域。随后在未损伤的麻醉动物中进行电生理实验，以研究电刺激MD诱发的PrL神经元短潜伏期和长潜伏期反应的调节。短潜伏期反应由MD-PrL通路激活引起，通过AMPA型谷氨酸能受体介导，而长潜伏期反应反映皮质锥体细胞的回返侧支激活。烟碱激动剂（尼古丁、二甲基苯基哌嗪）的离子电泳应用促进了这两种反应。局部应用nAChR拮抗剂二氢β-刺桐啶、美加明和甲基lycaconitine可阻止这两种促进作用。最后，进行脑内微透析实验，以检测PrL中细胞外谷氨酸浓度的烟碱调节作用。通过透析探针直接应用尼古丁以剂量依赖方式增加谷氨酸水平。这种作用被二氢β-刺桐啶的局部灌注所阻断。因此，这些发现为nAChR介导的对前额叶皮质丘脑皮质输入的调节提供了解剖学和功能证据。这种机制可能与尼古丁和烟碱拮抗剂的认知作用有关。
