Neuronal Signal Transduction Group, Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
International Max Planck Research School for Brain and Behavior, Jupiter, FL, USA.
Sci Adv. 2023 Aug 2;9(31):eadg0666. doi: 10.1126/sciadv.adg0666.
The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1 and 2 (IGF1 and IGF2) are differentially expressed in hippocampal neurons and released in an activity-dependent manner. Using a new fluorescence resonance energy transfer sensor for IGF1 receptor (IGF1R) with two-photon fluorescence lifetime imaging, we find that the release of IGF1 triggers rapid local autocrine IGF1R activation on the same spine and more than several micrometers along the stimulated dendrite, regulating the plasticity of the activated spine in CA1 pyramidal neurons. In CA3 neurons, IGF2, instead of IGF1, is responsible for IGF1R autocrine activation and synaptic plasticity. Thus, our study demonstrates the cell type-specific roles of IGF1 and IGF2 in hippocampal plasticity and a plasticity mechanism mediated by the synthesis and autocrine signaling of IGF peptides in pyramidal neurons.
胰岛素肽超级家族对于维持内环境稳态以及神经元的可塑性、学习和记忆至关重要。在这里，我们表明胰岛素样生长因子 1 和 2（IGF1 和 IGF2）在海马神经元中呈差异表达，并以活动依赖性方式释放。使用新的双光子荧光寿命成像荧光共振能量转移传感器用于 IGF1 受体（IGF1R），我们发现 IGF1 的释放会在同一棘突上触发快速的局部自分泌 IGF1R 激活，并且沿着受刺激的树突延伸超过几微米，调节 CA1 锥体神经元中激活棘突的可塑性。在 CA3 神经元中，IGF2 而不是 IGF1 负责 IGF1R 自分泌激活和突触可塑性。因此，我们的研究表明 IGF1 和 IGF2 在海马体可塑性中的细胞类型特异性作用，以及由 IGF 肽的合成和自分泌信号转导介导的可塑性机制在锥体神经元中。
