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.
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