Southern California Conferences for Undergraduate Research

Southern California Conferences for Undergraduate Research

MicroRNA124-Mediated Regulation of GluA2 in Mouse Hippocampal Neurons and its Role in Basal Synaptic Transmission


Liane Dallalzadeh, Victoria M Ho, Nestoras Karathanasis, Panayiota Poirazi


Kelsey C Martin, Professor and Chair of Biological Chemistry , University of California Los Angeles

Neurons are able to modify the strength of their synapses in response to the environment through a process called synaptic plasticity. Long-lasting forms of synaptic plasticity require new protein synthesis and can occur in a synapse-specific manner. We are interested in how neurons restrict gene expression to a subset of synapses and focus on the role of localized messenger RNAs (mRNAs) and their regulated translation. Based on computational predictions and previous studies, we hypothesized that translation of the AMPA receptor subunit GluA2 is inhibited by microRNA124 (miR-124) at distal subcellular regions. We have validated the GluA2 mRNA/miR-124 interaction via luciferase assays in 293T cells. Co-transfection of a GluA2 3’ UTR reporter with miR-124 resulted in a 50% knockdown of luciferase signal compared to control. Co-transfection with mutant reporters did not produce significant knockdown, indicating the repression of GluA2 mRNA by miR-124 is sequence-specific. We have also used fluorescence in situ hybridization to visualize GluA2 mRNA in dissociated mouse hippocampal neurons. The distribution of GluA2 mRNA puncta in dendrites was found to be significantly different (p<0.001) from that of Camk2α mRNA, a dendritically-localized control. Instead, the GluA2 mRNA distribution more closely followed that of somatically-restricted cFOS mRNA. These findings are consistent with our quantitative PCR studies on synaptosome preparations. Our results suggest that miR-124 and GluA2 mRNA may interact in the cell body, and not distally as originally hypothesized. Next, we will use gain and loss of function studies to determine if miR-124 inhibits GluA2 protein levels endogenously in neurons, and the effect of this interaction on basal transmission. We hope these studies will further our understanding of the mechanisms of long-lasting changes in synaptic strength that contribute to both learning and memory.

Presented by:

Liane Dallalzadeh


Saturday, November 17, 2012




Broome Library

Presentation Type:

Poster Presentation