Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala
Abstract Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-10-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-13674-9 |
| _version_ | 1818844050282774528 |
|---|---|
| author | Aniruddha Das Monica Dines Jessica M. Alapin Raphael Lamprecht |
| author_facet | Aniruddha Das Monica Dines Jessica M. Alapin Raphael Lamprecht |
| author_sort | Aniruddha Das |
| collection | DOAJ |
| description | Abstract Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase (PAK) are involved in such key neuronal functions. Here we show that optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation. Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation. Inhibition of PAK in LA by microinjection of the PAK inhibitor IPA-3 30 minutes before fear conditioning enhanced long-term but not short-term fear memory formation. Our results demonstrate that photoactivation of Rac1 GTPase in lateral amygdala impairs fear memory formation. Moreover, Rac1 effector PAK activity during fear conditioning constrains the formation of fear memory in LA. Thus, Rac GTPase and PAK proteins may serve as targets for treatment of fear and anxiety disorders. |
| first_indexed | 2024-12-19T05:07:36Z |
| format | Article |
| id | doaj.art-19cb94cb09fd48dd8843c432138bdd00 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T05:07:36Z |
| publishDate | 2017-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-19cb94cb09fd48dd8843c432138bdd002022-12-21T20:34:53ZengNature PortfolioScientific Reports2045-23222017-10-01711910.1038/s41598-017-13674-9Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdalaAniruddha Das0Monica Dines1Jessica M. Alapin2Raphael Lamprecht3Sagol Department of Neurobiology, Faculty of Natural Sciences,Sagol Department of Neurobiology, Faculty of Natural Sciences,Sagol Department of Neurobiology, Faculty of Natural Sciences,Sagol Department of Neurobiology, Faculty of Natural Sciences,Abstract Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase (PAK) are involved in such key neuronal functions. Here we show that optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation. Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation. Inhibition of PAK in LA by microinjection of the PAK inhibitor IPA-3 30 minutes before fear conditioning enhanced long-term but not short-term fear memory formation. Our results demonstrate that photoactivation of Rac1 GTPase in lateral amygdala impairs fear memory formation. Moreover, Rac1 effector PAK activity during fear conditioning constrains the formation of fear memory in LA. Thus, Rac GTPase and PAK proteins may serve as targets for treatment of fear and anxiety disorders.https://doi.org/10.1038/s41598-017-13674-9 |
| spellingShingle | Aniruddha Das Monica Dines Jessica M. Alapin Raphael Lamprecht Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala Scientific Reports |
| title | Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala |
| title_full | Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala |
| title_fullStr | Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala |
| title_full_unstemmed | Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala |
| title_short | Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala |
| title_sort | affecting long term fear memory formation through optical control of rac1 gtpase and pak activity in lateral amygdala |
| url | https://doi.org/10.1038/s41598-017-13674-9 |
| work_keys_str_mv | AT aniruddhadas affectinglongtermfearmemoryformationthroughopticalcontrolofrac1gtpaseandpakactivityinlateralamygdala AT monicadines affectinglongtermfearmemoryformationthroughopticalcontrolofrac1gtpaseandpakactivityinlateralamygdala AT jessicamalapin affectinglongtermfearmemoryformationthroughopticalcontrolofrac1gtpaseandpakactivityinlateralamygdala AT raphaellamprecht affectinglongtermfearmemoryformationthroughopticalcontrolofrac1gtpaseandpakactivityinlateralamygdala |