MicroRNAs (miRNAs) are small evolutionary conserved non-coding RNAs that have been shown to play an important role in brain development and synaptic plasticity. Brain expressed miRNAs are predicted to regulate at a posttranscriptional level the expression of multiple genes important for cortical plasticity. Deprivation of visual input from one or two eyes is a classical paradigm for studying experience-dependent cortical plasticity. However, the effect of sensory deprivation in miRNA expression in mouse visual cortex has not yet been investigated. This proposal focuses on elucidating the role of miRNAs in synaptic changes following dark rearing (DR) and monocular deprivation (MD) in mouse visual cortex. Specifically, we will first use microarrays to determine which miRNAs are altered in mouse primary visual cortex following dark rearing or monocular deprivation. We will then apply Locked nucleic acid- in situ hybridization and qRT-PCR to verify the changes in these experience-dependent miRNAs and more importantly determine their potential laminar or cellular specificity. Lentiviral induced overexpression of miRNAs that are reduced following monocular deprivation or dark rearing in mouse visual cortex will then be utilized. Following in vivo manipulation of MD-related miRNAs, electrophysiological recordings and optical imaging of intrinsic signals will first be used to study their effect on experience-dependent cortical plasticity. Lastly, in-vivo two-photon imaging will be carried out to determine if overexpression of both MD and DR related miRNAs has an effect in dendritic spine dynamics of primary visual cortex. This proposal will identify miRNAs that are altered in mouse visual cortex following monocular deprivation or dark rearing and explore their role in experience-dependent synaptic plasticity. My focus is to elucidate the importance of these novel small non coding RNAs that have already been linked to neuropsychiatric disease for mammalian cortical synaptic plasticity by using visual cortex development as a paradigm.
|Mellios, Nikolaos; Woodson, Jonathan; Garcia, Rodrigo I et al. (2014) ?2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A 111:9947-52|
|Mellios, Nikolaos; Sugihara, Hiroki; Castro, Jorge et al. (2011) miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. Nat Neurosci 14:1240-2|