Activation of Rho GTPases triggers structural remodeling and functional plasticity in the adult rat visual cortex.
A classical example of age-dependent plasticity is ocular dominance (OD) plasticity, triggered by monocular deprivation (MD). Sensitivity of cortical circuits to a brief period of MD is maximal in juvenile animals and downregulated in adult age. It remains unclear whether a reduced potential for morphological remodeling underlies this downregulation of physiological plasticity in adulthood. Here we have tested whether stimulation of structural rearrangements is effective in promoting experience-dependent plasticity in adult age. We have exploited a bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), that regulates actin dynamics and structure of neuronal processes via a persistent activation of Rho GTPases. Injection of CNF1 into the adult rat visual cortex triggered a long-lasting activation of the Rho GTPase Rac1, with a consequent increase in spine density and length in pyramidal neurons. Adult rats treated with CNF1, but not controls, showed an OD shift toward the open eye after MD. CNF1-mediated OD plasticity was selectively attributable to the enhancement of open-eye responses, whereas closed-eye inputs were unaffected. This effect correlated with an increased density of geniculocortical terminals in layer IV of monocularly deprived, CNF1-treated rats. Thus, Rho GTPase activation reinstates OD plasticity in the adult cortex via the potentiation of more active inputs from the open eye. These data establish a direct link between structural remodeling and functional plasticity and demonstrate a role for Rho GTPases in brain plasticity in vivo. The plasticizing effects of Rho GTPase activation may be exploited to promote brain repair.
CNR Neuroscience Institute, 56124 Pisa, Italy.
Chiara
C
Cerri
Alessia
A
Fabbri
Eleonora
E
Vannini
Maria
M
Spolidoro
Mario
M
Costa
Lamberto
L
Maffei
Carla
C
Fiorentini
Matteo
M
Caleo
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000201:enzymology; D023882:Dominance, Ocular / Q000187:drug effects / Q000502:physiology; D029968:Escherichia coli Proteins / Q000494:pharmacology; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D034781:Receptors, N-Acetylglucosamine / Q000378:metabolism; D012683:Sensory Deprivation / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D014793:Visual Cortex / Q000166:cytology* / Q000201:enzymology*; D014795:Visual Pathways / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D001427:Bacterial Toxins; D039481:CD11b Antigen; D029968:Escherichia coli Proteins; D004676:Myelin Basic Protein; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; C040129:wisteria lectin; C060296:cytotoxic necrotizing factor type 1; D020741:rho GTP-Binding Proteins; D010751:Phosphopyruvate Hydratase