Muscarinic modulation of the oscillatory and repetitive firing properties of entorhinal cortex layer II neurons
Muscarinic modulation of the oscillatory and repetitive firing properties of entorhinal cortex layer II neurons
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DOI：
10.1152/jn.1997.77.4.1813
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发表时间：
1997-04-01
影响因子：
2.5
通讯作者：
Alonso, A
中科院分区：
文献类型：
--
作者：
Klink, R;Alonso, A
内嗅皮层(EC)第二层神经元是颞叶记忆系统的关键成分，因为它们整合并转移到海马结构，汇聚来自整个皮质外套膜的感觉输入。EC II层也从基底前脑接受丰富的胆碱能神经支配，促进EC网络的振荡动力学，也可能实现记忆功能。为了了解EC胆碱能作用的细胞基础，我们在体外大鼠脑片上用细胞内记录的方法，研究了毒碱对两类不同类型的EC内侧II层投射神经元：星状细胞(SCs)和非SCs的电反应特性的调制。在SCs和非SCs中，用氨基甲胆碱(CCH，10-50mM)激活M受体可引起阿托品敏感的(300 NM)膜去极化。在SCs中，CCH诱导的膜去极化与阈值下膜电位振荡和“棘丛”放电有关，这是这些细胞在去极化时典型的表现。然而，CCH使膜电位振荡的主频从9.2+/-1.1(SD)赫兹降至6.3+/-1.1赫兹，并使簇内放电频率从18.1+/-1.7赫兹降至13.6+/-1.3赫兹。此外，在CCH期间，棘丛放电不那么强烈，细胞倾向于转移到紧张性放电。与干细胞不同，在非干细胞中，CCH通过促进电压依赖性、长时程(S 1-5)慢爆发动作电位的形成而显著影响放电行为，这些动作电位可以在低频率(0.2-0.5赫兹)有节律性地重复。相应地，慢后超极化(SAHP)被长时间的平台后去极化所取代。在SCs和非SCs中，CCH还引起动作电位波形及其后电位的明显变化。值得注意的是，CCH显著降低了棘波幅度和上升速率。这表明毒鼠碱对电压依赖的Na+电导有调制作用。最后，我们还观察到，CCH可使SCs和非SCs的SAHP消失，而3‘，5’-环磷酸腺苷、8-(4-氯苯硫基)-环磷酸腺苷和8-溴腺苷-环磷酸的膜结构类似物可使SCs的SAHP消失，但不影响非SCs的SAHP。数据表明，胆碱能调制进一步区分了干细胞和非干细胞的内在电反应，并支持内侧EC层II存在两个并行处理系统，从而可能对它们的海马靶产生不同的影响。结果还表明，胆碱能系统在调节内嗅神经元的振荡动力学中起着重要作用。
Neurons in layer II of the entorhinal cortex (EC) are key elements in the temporal lobe memory system because they integrate and transfer into the hippocampal formation convergent sensory input from the entire cortical mantle. EC layer II also receives a profuse cholinergic innervation from the basal forebrain that promotes oscillatory dynamics in the EC network and may also implement memory function. To understand the cellular basis of cholinergic actions in EC, we investigated by intracellular recording in an in vitro rat brain slice preparation the muscarinic modulation of the electroresponsive properties of the two distinct classes of medial EC layer II projection neurons; the stellate cells (SCs) and non-SCs. Ln both SCs and non-SCs, muscarinic receptor activation with carbachol (CCh, 10-50 mu M) caused atropine-sensitive (300 nM) membrane depolarization. In SCs, the CCh-induced membrane depolarization was associated with subthreshold membrane potential oscillations and ''spike cluster'' discharge, which are typically expressed by these cells on depolarization. CCh, however, caused a decrease of the dominant frequency of the membrane potential oscillations from 9.2 +/- 1.1 (SD) Hz to 6.3 +/- 1.1 Hz, as well as a decrease of the intracluster firing frequency from 18.1 +/- 1.7 Hz to 13.6 +/- 1.3 Hz. In addition, spike cluster discharge was less robust, and the cells tended to shift into tonic firing during CCh. Ln contrast to SCs, in non-SCs, CCh drastically affected firing behavior by promoting the development of voltage-dependent, long-duration (1-5 s) slow bursts of action potentials that could repeat rhythmically at slow frequencies (0.2-0.5 Hz). Concomitantly, the slow afterhyperpolarization (sAHP) was replaced by long-lasting plateau postdepolarizations. In both SCs and non-SCs, CCh also produced conspicuous changes on the action potential waveform and its afterpotentials. Notably, CCh significantly decreased spike amplitude and rate of rise. which suggests muscarinic modulation of a voltage-dependent Na+ conductance. Finally, we also observed that whereas CCh abolished the sAHP in both SCs and non-SCs, the membrane-permeant analogues of adenosine 3',5'-cyclic monophosphate, 8-(4-chlorophenylthio)-adenosine-cyclic monophosphate and 8-bromo-adenosine-cyclic-monophosphate, abolished the sAHP in SCs but not in non-SCs. The data demonstrate that cholinergic modulation further differentiates the intrinsic electroresponsiveness of SCs and non-SCs, and add support to the presence of two parallel processing systems in medial EC layer II that could thereby differentially influence their hippocampal targets. The results also indicate an important role for the cholinergic system in tuning the oscillatory dynamics of entorhinal neurons.