Identification of cofilin 1 as a candidate protein associated to mouse visual cortex plasticity.

In order to characterize the mechanisms controlling plasticity in the mouse visual cortex, we used, for the first time on brain samples, an unconventional proteomic approach to separate acid-extracted proteins by bi-dimensional electrophoresis (AUT/SDS or AUT/AU gels). The analysis was performed on high plasticity critical period young vs. low plasticity adult, and on fluoxetine-induced high plasticity vs. low plasticity untreated adult mice. Mass spectrometry allowed for the identification of 11 proteins that are differentially expressed between critical period and adult mice, and 5 between fluoxetine-treated and control adult mice. We then focused on cofilin 1, as the intensity level of the corresponding spot on 2D gels was higher in both high plasticity conditions. Western blot showed that cofilin 1 expression is dynamically regulated during postnatal life, reaching a peak at the critical period, and decreasing at adult stage, and that it increases in fluoxetine-treated vs. untreated adult mice. In summary, by using a 2D gel electrophoresis differential approach on basic proteins followed by mass spectrometry and immunoblot analysis, we identified cofilin 1 as a potential candidate controlling plasticity levels of the mouse visual cortex.

H3 and H4 Lysine Acetylation Correlates with Developmental and Experimentally Induced Adult Experience-Dependent Plasticity in the Mouse Visual Cortex.

Histone posttranslational modifications play a fundamental role in orchestrating gene expression. In this work, we analyzed the acetylation of H3 and H4 histones (AcH3-AcH4) and its modulation by visual experience in the mouse visual cortex (VC) during normal development and in two experimental conditions that restore juvenile-like plasticity levels in adults (fluoxetine treatment and enriched environment). We found that AcH3-AcH4 declines with age and is upregulated by treatments restoring plasticity in the adult. We also found that visual experience modulates AcH3-AcH4 in young and adult plasticity-restored mice but not in untreated ones. Finally, we showed that the transporter vGAT is downregulated in adult plasticity-restored models. In summary, we identified a dynamic regulation of AcH3-AcH4, which is associated with high plasticity levels and enhanced by visual experience. These data, along with recent ones, indicate H3-H4 acetylation as a central hub in the control of experience-dependent plasticity in the VC.

Creb is modulated in the mouse superior colliculus in developmental and experimentally-induced models of plasticity.

In the central nervous system long-term plastic processes need the activation of specific gene expression programs and the synthesis of new protein in order to occur. A transcription factor fundamental for several plasticity mechanisms in various CNS areas is the cAMP response element-binding protein, CREB. This factor is activated through phosphorylation at its Serine 133 residue by multiple signaling pathways. Little is known about CREB role in the superior colliculus, a midbrain area considered an experimentally useful model for the study of neuronal plasticity processes. In the present work we studied by Western blot analysis the modulation of CREB expression and activation in the mouse superior colliculus in three models of neuronal plasticity: (1) developmental plasticity; (2) lesion-induced plasticity; (3) and fluoxetine-induced restored plasticity. We used an antibody that detects endogenous level of the total CREB protein (anti-TCREB) to identify possible modulations at CREB expression level, and a second antibody (anti-PCREB) that detects endogenous level of CREB only when it is phosphorylated at Ser133, to identify modifications of CREB activation state. The results showed that: (1) the expression and activation of CREB increase during the development of the superior colliculus in temporal correlation with the plastic process of refinement of retino-collicular projections; (2) the activation of CREB is induced by a monocular lesion performed during the critical period for plasticity in young animals but not when performed in less plastic juvenile mice; (3) the expression and activation of CREB increase in adult animals treated with fluoxetine, known to restore high levels of plasticity in adult animals. These results suggest that CREB transcription factor plays a fundamental role in plasticity processes also at the level of the mouse superior colliculus.