Overexpression of Serum Response Factor Restores Ocular Dominance Plasticity in a Model of Fetal Alcohol Spectrum Disorders

Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in fetal alcohol spectrum disorders (FASD). Recently, we showed that third trimester alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. For instance, a few days of monocular deprivatio...

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Bibliographic Details
Published in:The Journal of neuroscience 2010-02, Vol.30 (7), p.2513-2520
Main Authors: Paul, Arco P, Pohl-Guimaraes, Fernanda, Krahe, Thomas E, Filgueiras, Claudio C, Lantz, Crystal L, Colello, Raymond J, Wang, Weili, Medina, Alexandre E
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Animals, Newborn
Diagnostic Imaging - methods
Dominance, Ocular - physiology
Ethanol - pharmacology
Ferrets
Glial Fibrillary Acidic Protein - metabolism
Green Fluorescent Proteins - genetics
Male
Microscopy, Confocal - methods
Neuronal Plasticity - drug effects
Neuronal Plasticity - physiology
Neurons - drug effects
Neurons - physiology
Phosphopyruvate Hydratase - metabolism
Sensory Deprivation - physiology
Serum Response Factor - genetics
Serum Response Factor - metabolism
Sindbis Virus - genetics
Transduction, Genetic - methods
Visual Cortex - cytology
Visual Cortex - metabolism
Visual Pathways - metabolism
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Summary:Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in fetal alcohol spectrum disorders (FASD). Recently, we showed that third trimester alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. For instance, a few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors such as the cAMP response element binding protein (CREB) and the serum response factor (SRF). SRF is important for many plasticity processes such as LTP, LTD, spine motility, and axonal pathfinding. Here we attempt to rescue OD plasticity in alcohol-treated ferrets using a Sindbis viral vector to express a constitutively active form of SRF during the period of monocular deprivation. Using optical imaging of intrinsic signals and single-unit recordings, we observed that overexpression of a constitutively active form of SRF, but neither its dominant-negative nor GFP, restored OD plasticity in alcohol-treated animals. Surprisingly, this restoration was observed throughout the extent of the primary visual cortex and most cells infected by the virus were positive for GFAP rather than NeuN. This finding suggests that overexpression of SRF in astrocytes may reduce the deficits in neuronal plasticity seen in models of FASD.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5840-09.2010