Local autocrine plasticity signaling in single dendritic spines by insulin-like growth factors

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.