Absence of Ca2+-stimulated adenylyl cyclases leads to reduced synaptic plasticity and impaired experience-dependent fear memory.
Absence of Ca2+-stimulated adenylyl cyclases leads to reduced synaptic plasticity and impaired experience-dependent fear memory.
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缺乏Ca2+刺激的腺苷循环酶会导致突触可塑性降低和经验依赖性的恐惧记忆。
DOI：
10.1038/tp.2012.50
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发表时间：
2012-05-29
影响因子：
6.8
通讯作者：
Muglia LJ
中科院分区：
文献类型：
--
作者：
Wieczorek L;Majumdar D;Wills TA;Hu L;Winder DG;Webb DJ;Muglia LJ
Ca2+-stimulated adenylyl cyclase (AC) 1 and 8 are two genes that have been shown to play critical roles in fear memory. AC1 and AC8 couple neuronal activity and intracellular Ca2+ increases to the production of cyclic adenosine monophosphate and are localized synaptically, suggesting that Ca2+-stimulated ACs may modulate synaptic plasticity. Here, we first established that Ca2+-stimulated ACs modulate protein markers of synaptic activity at baseline and after learning. Primary hippocampal cell cultures showed that AC1/AC8 double-knockout (DKO) mice have reduced SV2, a synaptic vesicle protein, abundance along their dendritic processes, and this reduction can be rescued through lentivirus delivery of AC8 to the DKO cells. Additionally, phospho-synapsin, a protein implicated in the regulation of neurotransmitter release at the synapse, is decreased in vivo 1 h after conditioned fear (CF) training in DKO mice. Importantly, additional experiments showed that long-term potentiation deficits present in DKO mice are rescued by acutely replacing AC8 in the forebrain, further supporting the idea that Ca2+-stimulated AC activity is a crucial modulator of synaptic plasticity. Previous studies have demonstrated that memory is continually modulated by gene–environment interactions. The last set of experiments evaluated the effects of knocking out AC1 and AC8 genes on experience-dependent changes in CF memory. We showed that the strength of CF memory in wild-type mice is determined by previous environment, minimal or enriched, whereas memory in DKO mice is unaffected. Thus, overall these results show that AC1 and AC8 modulate markers of synaptic activity and help integrate environmental information to modulate fear memory.
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影响因子：
25
作者：
Imayoshi, Itaru;Sakamoto, Masayuki;Kageyama, Ryoichiro
通讯作者：
Kageyama, Ryoichiro
影响因子：
5.3
作者：
Arruda-Carvalho, Maithe;Sakaguchi, Masanori;Frankland, Paul W.
通讯作者：
Frankland, Paul W.
影响因子：
64.8
作者：
Kempermann, G;Kuhn, HG;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1073/pnas.93.26.15451
发表时间：
1996-12-24
影响因子：
11.1
作者：
Nayak, AS;Moore, CI;Browning, MD
通讯作者：
Browning, MD
影响因子：
5.3
作者：
Jankowsky, JL;Melnikova, T;Savonenko, AV
通讯作者：
Savonenko, AV