Experience-dependent expression of NPAS4 regulates plasticity in adult visual cortex.
There is evidence that developmental-like plasticity can be reactivated in the adult visual cortex. Although activity-dependent transcription factors underlying the process of plasticity reactivation are currently unknown, recent studies point towards NPAS4 as a candidate gene for the occurrence of plasticity in the adult visual system. Here, we addressed whether NPAS4 is involved in the reinstatement of plasticity by using the monocular deprivation protocol and long-term fluoxetine treatment as a pharmacological strategy that restores plasticity in adulthood. A combination of molecular assays for gene expression and epigenetic analysis, gene delivery by lentiviral infection, shRNA interference and electrophysiology as a functional read-out, revealed a previously unknown role for the transcription factor NPAS4 in the regulation of adult visual cortical plasticity. We found that NPAS4 overexpression restores ocular dominance plasticity in adult naıve animals whereas NPAS4 down-regulation prevents the plastic outcome caused by fluoxetine in adulthood.Our findings lead the way to the identification of novel therapeutic targets for pathological conditions where reorganization of neuronal networks would be beneficial in adult life.
Scuola Normale Superiore, Neurobiology Laboratory, Piazza dei Cavalieri Pisa 56100 Italy. j.maya@sns.it
José Fernando
JF
Maya-Vetencourt
Ettore
E
Tiraboschi
Dario
D
Greco
Laura
L
Restani
Chiara
C
Cerri
Petri
P
Auvinen
Lamberto
L
Maffei
Eero
E
Castrén
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D019175:DNA Methylation; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D020318:Rats, Long-Evans; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; C516513:Npas4 protein, rat