Abstract：
: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 GABAA 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 GABAA 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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Jovasevic V,Corcoran KA,Leaderbrand K,Yamawaki N,Guedea AL,Chen HJ,Shepherd GM,Radulovic Jdoi
10.1038/nn.4084subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1265-71issue
9eissn
1097-6256issn
1546-1726pii
nn.4084journal_volume
18pub_type
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