Loss of CELF6 RNA binding protein impairs cocaine conditioned place preference and contextual fear conditioning. (19th June 2019)

• Record Type: Journal Article
• Authors: Maloney, Susan E.; Rieger, Michael A.; Al‐Hasani, Ream; Bruchas, Michael R.; Wozniak, David F.; Dougherty, Joseph D.
• Is Part Of: Genes, brain, and behavior. Volume 18:Number 7(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-06-19
• Subjects: behavior -- Celf6 -- cocaine -- conditioned place preference -- fear conditioning -- holeboard -- mouse -- resistance to change -- reward -- RNA binding protein; Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12593
• Languages: English
• ISSNs: 1601-1848

Abstract

Abstract: In addition to gene expression differences in distinct cell types, there is substantial post‐transcriptional regulation driven in part by RNA binding proteins (RBPs). Loss‐of‐function RBP mutations have been associated with neurodevelopmental disorders, such as Fragile‐X syndrome and syndromic autism. Work performed in animal models to elucidate the influence of neurodevelopmental disorder‐associated RBPs on distinct behaviors has showed a connection between normal post‐transcriptional regulation and conditioned learning. We previously reported cognitive inflexibility in a mouse model null for the RBP CUG‐BP, Elav‐like factor 6 (CELF6), which we also found to be associated with human autism. Specifically, these mice failed to potentiate exploratory hole‐poking behavior in response to familiarization to a rewarding stimuli. Characterization of Celf6 gene expression showed high levels in monoaminergic populations such as the dopaminergic midbrain populations. To better understand the underlying behavioral disruption mediating the resistance to change exploratory behavior in the holeboard task, we tested three hypotheses: Does Celf6 loss lead to global restricted patterns of behavior, failure of immediate response to reward or failure to alter behavior in response to reward (conditioning). We found the acute response to reward was intact, yet Celf6 mutant mice exhibited impaired conditioned learning to both reward and aversive stimuli. Thus, we found that the resistance to change by the Celf6 mutant in the holeboard was most parsimoniously explained as a failure of conditioning, as the mice had blunted responses even to potent rewarding stimuli such as cocaine. These findings further support the role of RBPs in conditioned learning. Abstract : Mice lacking of the RNA binding protein Celf6 do not condition to the rewarding substance cocaine and show deficits to fear conditioning.