SUMMARYInsulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, degenerative diseases, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal activity in many areas of the brain, its effect on synaptic plasticity and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the infralimbic cortex. Besides, IGF-1 mediates a long-term depression of both inhibitory and excitatory synaptic transmission that results in a longterm potentiation of the postsynaptic potentials. We demonstrate that these synaptic and intrinsic regulatory processes mediated by IGF-1 favor the fear extinction memory. These results show novel functional consequences of IGF-1 signaling on animal behavior tasks dependent on the prefrontal cortex, revealing IGF-1 as a key element in the control of the fear extinction memory.Impact StatementIGF-1 modulates the neuronal firing and synaptic plasticity in infralimbic cortex, favoring the extinction memory
Faculty Opinions recommendation of Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats.