Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of function of the Fragile X Mental Retardation Protein (FMRP). Studies of FXS patients and mouse models of FXS suggest that FMRP is critical for proper synaptic function and plasticity. I propose to investigate the role of FMRP in synaptic function through three major aims: 1) Electrophysiological measurements of synaptic function following transient alteration of FMRP expression levels in organotypic hippocampal slice cultures (OHSCs) and through the use of FMRP mutants; 2) Electrophysiological analysis of synaptic plasticity in FMRP-overexpressing mice and in OHSCs following transient overexpression of FMRP and FMRP mutants; and 3) Biochemical analysis of glutamate receptor expression and trafficking in FMRP-overexpressing and FMRP-knockout mice and in OHSCs following transient alterations in FMRP expression. This research should give substantial insight into the role of FMRP at the synapse and may provide impetus for the generation of a treatment for FXS. ? ?
| Pfeiffer, Brad E; Zang, Tong; Wilkerson, Julia R et al. (2010) Fragile X mental retardation protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron 66:191-7 |
| Pfeiffer, Brad E; Huber, Kimberly M (2009) The state of synapses in fragile X syndrome. Neuroscientist 15:549-67 |
| Waung, Maggie W; Pfeiffer, Brad E; Nosyreva, Elena D et al. (2008) Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron 59:84-97 |
| Volk, Lenora J; Pfeiffer, Brad E; Gibson, Jay R et al. (2007) Multiple Gq-coupled receptors converge on a common protein synthesis-dependent long-term depression that is affected in fragile X syndrome mental retardation. J Neurosci 27:11624-34 |
| Pfeiffer, Brad E; Huber, Kimberly M (2007) Fragile X mental retardation protein induces synapse loss through acute postsynaptic translational regulation. J Neurosci 27:3120-30 |
