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Analysis of the roles of NO-cGMP signaling cascade for long-term memory formation in an insect.

分析 NO-cGMP 信号级联对昆虫长期记忆形成的作用。

基本信息

批准号：
15370031
负责人：
MIZUNAMI Makoto
金额：
$ 8.38万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15370031/
关键词：
Cricket Olfactory learning Nitric oxide Long-term memory Cyclic GMP Insect Cyclic AMP カルモジュリンタンパク合成阻害剤

项目摘要

Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. The aim of this study was to clarify the roles of the NO-cGMP pathway for the LTM formation. We have studied the signaling cascade underlying LTM formation by systematically co-injecting various 'LTM-inducing' and 'LTM-blocking' drugs in crickets. Multiple-trial olfactory conditioning led to LTM that lasted for several days, while memory induced by single-trial conditioning decayed away within several hours. Injection of inhibitors of the enzyme forming NO, cGMP or cAMP into the hemolymph prior to multiple-trial conditioning blocked LTM, whereas injection of an NO donor, cGMP analogue or cAMP analogue prior to single-trial conditioning induced LTM. Induction of LTM by injection of an NO donor or cGMP analogue paired with single-trial conditioning was blocked by inhibitors of the cAMP pathway, but induction of LTM by a cAMP analogue was unaffected by inhibitors of the NO-cGMP pathway. Inhibitors of cyclic nucleotide gated channel (CNG channel) or calmodulin blocked induction of LTM by cGMP analogue paired with single-trial conditioning, but they did not affect induction of LTM by cAMP analogue. This study suggests, for the first time, that the cAMP pathway is a downstream target of the NO-cGMP pathway for the formation of LTM and that the CNG channel and calcium-calmodulin intervene between the NO-cGMP pathway and the cAMP pathway.

环磷酸腺苷通路在长时记忆的形成中起着至关重要的作用。在一些物种中，一氧化氮(NO)-环状GMP途径被发现在LTM形成过程中与cAMP途径平行和互补。本研究的目的是阐明NO-cGMP途径在LTM形成中的作用。我们通过系统地在蟋蟀体内注射不同的“LTM诱导”和“LTM阻断”药物来研究LTM形成的信号级联。多次尝试的嗅觉调节导致LTM持续数天，而单次尝试的条件反射诱导的记忆在几个小时内衰退。在多次条件作用前向血淋巴中注射形成NO、cGMP或cAMP的酶抑制剂可阻断LTM，而在单次条件作用前注射NO供体、cGMP类似物或cAMP类似物则可诱导LTM。注射NO供体或cGMP类似物结合单次条件作用可被cAMP途径的抑制剂阻断，但cAMP类似物诱导的LTM不受NO-cGMP途径抑制剂的影响。环核苷酸门控通道(CNG通道)或钙调素拮抗剂可阻断cGMP类似物结合单次条件反射诱导的LTM，但不影响cAMP类似物对LTM的诱导。本研究首次表明，cAMP途径是NO-cGMP途径下游形成LTM的靶点，CNG通道和钙-钙调蛋白参与了NO-cGMP途径和cAMP途径之间的相互作用。