Developing successful treatments for cognitive disorders such as dementia is a major goal in neuroscience. Key to the development of novel therapeutics for cognitive disorders is the understanding of the molecular and cellular basis of how memories are encoded, maintained and eventually erased. Here we propose to study the contribution of a novel class of candidates, long-noncoding RNAs (lncRNAs), to contextual fear memory, a form of associative memory in which an animal forms strong association of a fearful experience to a context. Because of the potential roles of lncRNAs as regulators of transcription and translation, elucidating lncRNA function in neuronal communication and long-term memory (LTM) storage will facilitate identification of novel targets for developing therapeutics for cognitive disorders. The central hypothesis of this proposal, based on our own preliminary data, is that specific changes in the expression of lncRNAs in the hippocampus mediate the consolidation of contextual fear memories. To test this hypothesis, we will use the contextual fear-conditioning (CFC) paradigm that produces long-lasting fear memories in mice as a behavioral assay and then determine whether expression of specific lncRNAs in CA1, CA3 and dentate gyrus (DG) neurons of the hippocampus are critical for the consolidation of contextual fear memories. An anticipated outcome of this proposed research is that once the specific lncRNAs that are regulated during contextual fear memory storage are identified, they may be manipulated pharmacologically, producing new and innovative approaches to the treatment of disorders such as post-traumatic disorders.
Presently, there is no cure for mental illnesses such as post-traumatic disorders (PTSDs). This proposal outlines experiments designed to understand the role of long noncoding RNAs (lncRNAs) in the tri-synaptic circuitry of the hippocampus in the consolidation of contextual fear memories. Once key lncRNAs involved in contextual fear memories are identified, they may be manipulated pharmacologically, producing new and innovative approaches to the treatment of mental illnesses such as PTSDs.
| Raveendra, Bindu L; Swarnkar, Supriya; Avchalumov, Yosef et al. (2018) Long noncoding RNA GM12371 acts as a transcriptional regulator of synapse function. Proc Natl Acad Sci U S A 115:E10197-E10205 |
