Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11.
Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11.
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DOI：
10.1038/mp.2012.130
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发表时间：
2013-10
影响因子：
11
通讯作者：
Svenningsson, P.
中科院分区：
文献类型：
--
作者：
Eriksson, T. M.;Alvarsson, A.;Stan, T. L.;Zhang, X.;Hascup, K. N.;Hascup, E. R.;Kehr, J.;Gerhardt, G. A.;Warner-Schmidt, J.;Arango-Lievano, M.;Kaplitt, M. G.;Ogren, S. O.;Greengard, P.;Svenningsson, P.
认知障碍在抑郁症中很常见，涉及血清素神经传递功能障碍。5-HT 1B受体（5-HT 1BR）通过突触前受体调节5-羟色胺的传递，但也可以影响异突触部位的递质释放。本研究旨在通过使用p11基因敲除（p11 KO）小鼠（抑郁相关状态的遗传模型），研究5-HT 1BR及其衔接蛋白p11在情绪记忆和物体识别记忆过程中的作用。5-HT 1BR激动剂处理诱导了对野生型（WT）小鼠的情绪记忆的损害作用。相比之下，p11 KO小鼠表现出长期情绪记忆能力下降。出乎意料的是，5-HT 1BR激动剂刺激增强了p11 KO小鼠的记忆，并且在海马腺相关病毒介导的p11基因转移后，这种非典型开关被逆转。值得注意的是，5-HT 1BR刺激增加了p11 KO小鼠海马中的突触能神经传递，但在WT小鼠中没有，这是通过突触前和突触后标准测量的。磁共振波谱表明，全球海马减少抑制GABA，这可能有助于记忆增强和增强的前和突触后谷氨酸传输的措施，由5-HT 1BR激动剂在p11 KO小鼠。结论：海马p11的水平决定了5-HT 1BR作用于情绪记忆加工的方向性，并调节海马的功能。这些结果强调了使用相关的疾病模型时，评估5-羟色胺神经传递的作用，在认知功能障碍相关的精神疾病的重要性。
Cognitive impairments are common in depression and involve dysfunctional serotonin neurotransmission. The 5-HT1B receptor (5-HT1BR) regulates serotonin transmission, via presynaptic receptors, but can also affect transmitter release at heterosynaptic sites. This study aimed at investigating the roles of the 5-HT1BR, and its adapter protein p11, in emotional memory and object recognition memory processes by the use of p11 knockout (p11KO) mice, a genetic model for aspects of depression-related states. 5-HT1BR agonist treatment induced an impairing effect on emotional memory in wild type (WT) mice. In comparison, p11KO mice displayed reduced long-term emotional memory performance. Unexpectedly, 5-HT1BR agonist stimulation enhanced memory in p11KO mice, and this atypical switch was reversed after hippocampal adeno-associated virus mediated gene transfer of p11. Notably, 5-HT1BR stimulation increased glutamatergic neurotransmission in the hippocampus in p11KO mice, but not in WT mice, as measured by both pre- and postsynaptic criteria. Magnetic resonance spectroscopy demonstrated global hippocampal reductions of inhibitory GABA, which may contribute to the memory enhancement and potentiation of pre- and post-synaptic measures of glutamate transmission by a 5-HT1BR agonist in p11KO mice. It is concluded that the level of hippocampal p11 determines the directionality of 5-HT1BR action on emotional memory processing and modulates hippocampal functionality. These results emphasize the importance of using relevant disease models when evaluating the role of serotonin neurotransmission in cognitive deficits related to psychiatric disorders.
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影响因子：
7.6
作者：
Åhlander-Lüttgen, M;Madjid, N;Ögren, SO
通讯作者：
Ögren, SO
影响因子：
4.7
作者：
Harmer, Catherine J.
通讯作者：
Harmer, Catherine J.
DOI：
10.1073/pnas.0337481100
发表时间：
2003-02-04
影响因子：
11.1
作者：
MacQueen, GM;Campbell, S;Young, LT
通讯作者：
Young, LT
影响因子：
17.1
作者：
Alexander B;Warner-Schmidt J;Eriksson T;Tamminga C;Arango-Lievano M;Ghose S;Vernov M;Stavarache M;Musatov S;Flajolet M;Svenningsson P;Greengard P;Kaplitt MG
通讯作者：
Kaplitt MG
DOI：
10.1098/rstb.1997.0154
发表时间：
1997-11-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Ledoux, JE;Muller, J
通讯作者：
Muller, J