Muscarinic suppression in stratum radiatum of CA1 shows dependence on presynaptic M1 receptors and is not dependent on effects at GABAB receptors
Muscarinic suppression in stratum radiatum of CA1 shows dependence on presynaptic M1 receptors and is not dependent on effects at GABAB receptors
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DOI：
10.1016/j.nlm.2005.09.005
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发表时间：
2006-03-01
影响因子：
2.7
通讯作者：
Hasselmo, ME
中科院分区：
文献类型：
--
作者：
Kremin, T;Gerber, D;Hasselmo, ME
胆碱能对突触传递的调节对记忆过程至关重要，可能负责在海马体中设置适合信息编码的网络动力学。Sheridan和Sutor(1990)发现证据表明M1受体导致谷氨酸能传递的突触前抑制，而Dutar和Nicoll(1988a)的研究支持M2受体的作用。与野生型(WT)对照相比，我们研究了M1亚型受体(KO)缺失的小鼠辐射层中fEPSP的毒碱抑制作用。与KO相比，WT小鼠表现出更大的剂量依赖性地抑制毒蛾碱的传播。而M1激动剂MCN-A-343对KO和KO的抑制作用有显著差异，KO无抑制作用。100微摩尔的选择性GABA拮抗剂SGS-742既不能影响WT或KO的正常传递，也不能影响毒碱抑制，这表明这两组之间的抑制差异不是由于GABA能中间神经元的毒碱激活导致的GABA(B)受体激活的差异。这些发现支持突触前nIL mAChRs在CA1区突触传递的调节中的作用，但也表明其他M受体亚型，如M2，也参与了突触电位的抑制。(C)2005 Elsevier Inc.保留所有权利。
Cholinergic modulation of synaptic transmission is vital to memory processes and may be responsible for setting network dynamics in the hippocampus appropriate for encoding of information. Sheridan and Sutor (1990) found evidence Suggesting M1 receptors cause presynaptic inhibition of glutamatergic transmission, while Dutar and Nicoll (1988a) research supports a role of the M2 receptor. We exarnined muscarinic inhibition of fEPSPs in stratum radiatum of mice lacking m1 subtype receptors (KO) compared to wild type (WT) controls. WT mice exhibit greater Suppression of transmission by muscarine as compared to KO in a dose dependent fashion. Oxotremorine shows no significant difference in suppression between WT and KO, while MCN-A-343, an M1 agonist, exhibits a significant difference between KO and WT, with KO showing no Suppression. One hundred micromolar SGS-742, a selective GABA, antagonist, fails to affect either normal transmission or muscarinic Suppression in either WT or KO suggesting that differences in Suppression between the groups is not attributable to differences in GABA(B) receptor activation due to muscarinic activation of GABAergic interneurons. These findings Support a role for presynaptic nil mAChRs in modulation of synaptic transmission in CA1, but indicate that other muscarinic receptor subtypes, Such as M2, are also involved in suppression of synaptic potentials. (c) 2005 Elsevier Inc. All rights reserved.