Visual experience regulates transient expression and dendritic localization of fragile X mental retardation protein.
Fragile X syndrome is the most common form of inherited mental retardation and is caused by the loss of function of the Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein thought to play a key role in protein synthesis-dependent synaptic plasticity. The regulation of FMRP expression itself is also likely to be an important control point in this process. Here we used dark-reared/light-exposed rats to determine the role of experience in regulating FMRP levels in the visual cortex. We find that FMRP levels increase in the cell bodies and dendrites of visual cortical neurons after as little as 15 min of light exposure. Remarkably, FMRP expression in these neurons returns to baseline levels by 30 min of light exposure. These changes were post-transcriptional because the FMR1 mRNA levels remained constant over this time period. A transient increase in FMRP levels was also observed in synaptic fractions prepared from visual cortices of light-exposed animals. In contrast, alpha-calcium/calmodulin-dependent kinase II expression showed a sustained upregulation under these conditions. Finally, the increase in FMRP expression was inhibited by blockade of NMDA receptors. This tight temporal-spatial regulation suggests that FMRP plays a dynamic role in a distinct epoch of experience-dependent synaptic plasticity.
Gabel
Lisa A
LA
Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.
Won
Sandra
S
Kawai
Hideki
H
McKinney
Margaret
M
Tartakoff
Alan M
AM
Fallon
Justin R
JR
D000818:Animals; D003624:Darkness; D003712:Dendrites / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1; D007150:Immunohistochemistry; D008027:Light; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010775:Photic Stimulation; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014793:Visual Cortex / Q000166:cytology / Q000378:metabolism*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C497685:Fmr1 protein, rat