Insulin-like growth factor-I (IGF-I) signalling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signalling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTP, here called LTPIGFI) of the postsynaptic potentials that is caused by a long-term depression (LTD) of inhibitory synaptic transmission in mice. We have demonstrated that this long-lasting decrease in the inhibitory transmission is evoked by astrocytic activation through its IGF-IRs. We show that LTPIGFI not only increases the output of pyramidal neurons, but also favours the N-methyl-D-aspartate (NMDAR) dependent LTP, resulting in the crucial information processing at the Barrel cortex since specific deletion of IGF-IR in cortical astrocytes (IGF-IR-/-) impairs the whisker discrimination task. Our work reveals a novel mechanism and functional consequenc...