%0 Journal Article %T Cortical nitric oxide required for presynaptic long-term potentiation in the insular cortex. %A Yamamoto K %A Chen QY %A Zhou Z %A Kobayashi M %A Zhuo M %J Philos Trans R Soc Lond B Biol Sci %V 379 %N 1906 %D 2024 Jul 29 %M 38853563 %F 6.671 %R 10.1098/rstb.2023.0475 %X Nitric oxide (NO) is a key diffusible messenger in the mammalian brain. It has been proposed that NO may diffuse retrogradely into presynaptic terminals, contributing to the induction of hippocampal long-term potentiation (LTP). Here, we present novel evidence that NO is required for kainate receptor (KAR)-dependent presynaptic form of LTP (pre-LTP) in the adult insular cortex (IC). In the IC, we found that inhibition of NO synthase erased the maintenance of pre-LTP, while the induction of pre-LTP required the activation of KAR. Furthermore, NO is essential for pre-LTP induced between two pyramidal cells in the IC using the double patch-clamp recording. These results suggest that NO is required for homosynaptic pre-LTP in the IC. Our results present strong evidence for the critical roles of NO in pre-LTP in the IC. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.