NMDA and AMPA receptors contribute to the nicotinic cholinergic excitation of CA1 Interneurons in the rat hippocampus
NMDA and AMPA receptors contribute to the nicotinic cholinergic excitation of CA1 Interneurons in the rat hippocampus
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DOI：
10.1152/jn.00214.2003
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发表时间：
2003-09-01
影响因子：
2.5
通讯作者：
Albuquerque, EX
中科院分区：
文献类型：
--
作者：
Alkondon, M;Pereira, EFR;Albuquerque, EX
在海马区，谷氨酸能神经元和中间神经元的谷氨酸能输入分别受谷氨酸能神经元上存在的α7*和α3β4*烟碱型乙酰胆碱受体(NAChRs)的调节。本研究探讨了烟碱型AMPA和NMDA受体nAChR活性如何整合来调节大鼠海马片CA1放射层(SR)中间神经元的兴奋性。在静止膜电位和细胞外镁离子(1 MM)存在下，烟碱能激动剂在SR神经元间兴奋性突触后电流(EPSCs)中被触发，该电流有两种成分：一种由AMPA受体介导，另一种由NMDA受体介导。如前所述，尼古丁激动剂触发的EPSCs是通过激活谷氨酸能神经元/纤维中的α3β4*nAChRs释放的谷氨酸引起的，这些神经元/纤维直接与被研究的神经元突触。通过阻断突触后AMPA受体，CNQX对尼古丁激动剂触发的EPSCs的抑制作用超过预期，表明这种尼古丁反应还依赖于突触到中间神经元的谷氨酸能神经元中AMPA受体的活性。烟碱激动剂总是触发CA1SR中间神经元的动作电位。在大多数中间神经元中，这些动作电位是由躯体树突状AMPA受体和α7*nAChRs激活引起的。在表达躯体树突状α4beta2*nAChRs的中间神经元中，这些受体的激活引起足够的膜去极化，以消除镁离子诱导的躯体树突状NMDA受体的阻断；在这些神经元中，尼古丁激动剂触发的动作电位部分依赖于NMDA受体的激活。清除细胞外的镁离子或以正的膜电位钳制神经元表明，SR中间神经元存在紧张性NMDA电流，该电流不受nAChR激活或抑制的影响。因此，nAChRs、NMDA和AMPA受体在CA1神经元不同区段的整合有助于提高CA1SR中间神经元的兴奋性。
In the hippocampus, glutamatergic inputs to pyramidal neurons and interneurons are modulated by alpha7* and alpha3beta4* nicotinic acetylcholine receptors (nAChRs), respectively, present in glutamatergic neurons. This study examines how nicotinic AMPA, and NMDA receptor nAChR activities are integrated to regulate the excitability of CA1 stratum radiatum (SR) interneurons in rat hippocampal slices. At resting membrane potentials and in the presence of extracellular Mg2+ ( 1 mM), nicotinic agonists triggered in SR interneurons excitatory postsynaptic currents (EPSCs) that had two components: one mediated by AMPA receptors, and the other by NMDA receptors. As previously shown, nicotinic agonist - triggered EPSCs resulted from glutamate released by activation of alpha3beta4* nAChRs in glutamatergic neurons/fibers synapsing directly onto the neurons under study. The finding that CNQX caused more inhibition of nicotinic agonist - triggered EPSCs than expected from the blockade of postsynaptic AMPA receptors indicated that this nicotinic response also depended on the AMPA receptor activity in the glutamatergic neurons synapsing onto the interneuron under study. Nicotinic agonists always triggered action potentials in CA1 SR interneurons. In most interneurons, these action potentials resulted from activation of somatodendritic AMPA receptors and alpha7* nAChRs. In interneurons expressing somatodendritic alpha4beta2* nAChRs, activation of these receptors caused sufficient membrane depolarization to remove the Mg2+-induced block of somatodendritic NMDA receptors; in these neurons, nicotinic agonist - triggered action potentials were partially dependent on NMDA receptor activation. Removing extracellular Mg2+ or clamping the neuron at positive membrane potentials revealed the existence of a tonic NMDA current in SR interneurons that was unaffected by nAChR activation or inhibition. Thus integration of the activities of nAChRs, NMDA, and AMPA receptors in different compartments of CA1 neurons contributes to the excitability of CA1 SR interneurons.