GABAergic mechanisms regulated by MIR-33 encode state-dependent fear

Vladimir Jovasevic, Kevin A. Corcoran, Katherine Leaderbrand, Naoki Yamawaki, Anita L. Guedea, Helen J. Chen, Gordon M.G. Shepherd, Jelena Radulovic*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar. Restricted access to such memories can present a risk for psychiatric disorders and hamper their treatment. To better understand the mechanisms underlying state-dependent fear, we used a mouse model of contextual fear conditioning. We found that heightened activity of hippocampal extrasynaptic GABA A receptors, believed to impair fear and memory, actually enabled their state-dependent encoding and retrieval. This effect required protein kinase C-βII and was influenced by miR-33, a microRNA that regulates several GABA-related proteins. In the extended hippocampal circuit, extrasynaptic GABA A receptors promoted subcortical, but impaired cortical, activation during memory encoding of context fear. Moreover, suppression of retrosplenial cortical activity, which normally impairs retrieval, had an enhancing effect on the retrieval of state-dependent fear. These mechanisms can serve as treatment targets for managing access to state-dependent memories of stressful experiences.

Original languageEnglish (US)
Pages (from-to)1265-1271
Number of pages7
JournalNature neuroscience
Issue number9
StatePublished - Aug 26 2015

ASJC Scopus subject areas

  • General Neuroscience


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