Somatostatin Signaling in Neuronal Cilia Is Critical for Object Recognition Memory
Somatostatin Signaling in Neuronal Cilia Is Critical for Object Recognition Memory
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DOI：
10.1523/jneurosci.5295-09.2010
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发表时间：
2010-03-24
影响因子：
5.3
通讯作者：
Tallent, Melanie K.
中科院分区：
文献类型：
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作者：
Einstein, Emily B.;Patterson, Carlyn A.;Tallent, Melanie K.
大多数神经元具有从细胞表面突出的单个不动的纤毛。这些基于微管的细胞器在大脑发育和神经发生中很重要;然而，它们在成熟神经元中的功能尚不清楚。纤毛表达与其他神经元区室不同的蛋白质的补充，其中之一是生长抑素受体亚型SST 3。我们在这里表明，SST 3对小鼠的物体识别记忆至关重要。SST 3敲除小鼠在辨别新物体方面严重受损，而它们对物体位置保持正常记忆。此外，全身注射SST 3拮抗剂（ACQ 090）破坏了野生型小鼠对熟悉物体的回忆。为了研究SST 3的机制，我们测试了海马CA 1区的突触可塑性。电诱发的长时程增强（LTP）是正常的sst 3基因敲除小鼠，而腺苷酸环化酶/cAMP介导的LTP受损。SST 3拮抗剂也破坏cAMP介导的LTP。与野生型小鼠相比，sst 3基因敲除小鼠海马裂解物中的基础cAMP水平降低，而毛喉素诱导的cAMP水平升高是正常的。SST 3拮抗剂抑制毛喉素刺激的cAMP增加，而SST 3激动剂L-796，778增加海马切片中的基础cAMP水平，但不增加海马裂解物。我们的研究结果表明，生长抑素信号在神经元纤毛识别记忆是至关重要的，并建议cAMP途径是一个保守的纤毛信号基序。因此，神经元纤毛代表了一种新的非突触区室，对参与特定形式的突触可塑性和新奇检测的信号传导至关重要。
Most neurons possess a single, nonmotile cilium that projects out from the cell surface. These microtubule-based organelles are important in brain development and neurogenesis; however, their function in mature neurons is unknown. Cilia express a complement of proteins distinct from other neuronal compartments, one of which is the somatostatin receptor subtype SST3. We show here that SST3 is critical for object recognition memory in mice. sst3 knock-out mice are severely impaired in discriminating novel objects, whereas they retain normal memory for object location. Further, systemic injection of an SST3 antagonist (ACQ090) disrupts recall of familiar objects in wild-type mice. To examine mechanisms of SST3, we tested synaptic plasticity in CA1 hippocampus. Electrically evoked long-term potentiation (LTP) was normal in sst3 knock-out mice, while adenylyl cyclase/cAMP-mediated LTP was impaired. The SST3 antagonist also disrupted cAMP-mediated LTP. Basal cAMP levels in hippocampal lysate were reduced in sst3 knock-out mice compared with wild-type mice, while the forskolin-induced increase in cAMP levels was normal. The SST3 antagonist inhibited forskolin-stimulated cAMP increases, whereas the SST3 agonist L-796,778 increased basal cAMP levels in hippocampal slices but not hippocampal lysate. Our results show that somatostatin signaling in neuronal cilia is critical for recognition memory and suggest that the cAMP pathway is a conserved signaling motif in cilia. Neuronal cilia therefore represent a novel nonsynaptic compartment crucial for signaling involved in a specific form of synaptic plasticity and in novelty detection.