Fernández de Sevilla David, Núñez Angel, Borde Michel, Malinow Roberto, Buño Washington
Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
J Neurosci. 2008 Feb 6;28(6):1469-78. doi: 10.1523/JNEUROSCI.2723-07.2008.
Cholinergic-glutamatergic interactions influence forms of synaptic plasticity that are thought to mediate memory and learning. We tested in vitro the induction of long-lasting synaptic enhancement at Schaffer collaterals by acetylcholine (ACh) at the apical dendrite of CA1 pyramidal neurons and in vivo by stimulation of cholinergic afferents. In vitro ACh induced a Ca2+ wave and synaptic enhancement mediated by insertion of AMPA receptors in spines. Activation of muscarinic ACh receptors (mAChRs) and Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores were required for this synaptic enhancement that was insensitive to blockade of NMDA receptors and also triggered by IP3 uncaging. Activation of cholinergic afferents in vivo induced an analogous atropine-sensitive synaptic enhancement. We describe a novel form of synaptic enhancement (LTP(IP3)) that is induced in vitro and in vivo by activation of mAChRs. We conclude that Ca2+ released from postsynaptic endoplasmic reticulum stores is the critical event in the induction of this unique form of long-lasting synaptic enhancement.
胆碱能 - 谷氨酸能相互作用影响被认为介导记忆和学习的突触可塑性形式。我们在体外测试了乙酰胆碱（ACh）在CA1锥体神经元顶端树突的Schaffer侧支诱导持久突触增强的情况，并在体内通过刺激胆碱能传入神经进行了测试。在体外，ACh诱导了一个Ca2+波以及由AMPA受体插入棘突介导的突触增强。毒蕈碱型ACh受体（mAChRs）的激活和从肌醇1,4,5 - 三磷酸（IP3）敏感储存库释放Ca2+是这种突触增强所必需的，这种增强对NMDA受体阻断不敏感，并且也可由IP3解笼触发。体内胆碱能传入神经的激活诱导了类似的对阿托品敏感的突触增强。我们描述了一种新型的突触增强形式（LTP(IP3)），它在体外和体内均可由mAChRs的激活诱导产生。我们得出结论，从突触后内质网储存库释放的Ca2+是诱导这种独特形式的持久突触增强的关键事件。
