Presentation Title: Silencing of the neuronal nitric oxide synthase gene in the basolateral amygdala impairs cued fear memory consolidation
Author Name(s): Jheel Patel1,2,3, Erik T Dustrude2,3, Andrei I Molosh2,3, Anantha Shekhar1,2,3,4
Author Department and School Affiliation: 1Medical Neuroscience Graduate Program; 2Paul and Carole Stark Neurosciences Research Institute; 3Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN;4Indiana Clinical and Translation Sciences Institute, Indiana University School of Medicine, Indianapolis, IN
Abstract: Fear and anxiety are evolutionarily developed responses to perceived or anticipated threats. Normal learning can produce avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Involvement of the amygdala in fear acquisition is very well described and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process that is mediated by interaction between postsynaptic density protein 95 (PSD95) and nitric oxide synthase (nNOS). To further understand the role of the PSD95-nNOS-NO pathway in cued fear, we utilized an adeno-associated virus mediated knockdown of the nNos gene (or scrambled siRNA for control) in the basolateral amygdala (BLA) of Sprague-Dawley rats. We found no differences between control and nNos-knockdown rats in their locomotor activity, spatial memory, social interaction, anxiety-like behavior, and cued fear acquisition. However, cued fear consolidation was significantly attenuated in nNos-knockdown rats. Our results reveal that nNOS in the BLA is a novel genetic target underlying the mechanism of cued fear consolidation and can inform future therapeutic strategies for targeting fear and anxiety related disorders like PTSD.
Acknowledgements: This project was supported by the Indiana Clinical and Translational Sciences Institute funded, in part, by Grant Number TL1TR002531 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award; by the Paul and Carole Stark Fellowship to JP; and R21 MH104018, MH052619 and R44 MH103936 to AS.