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Biomedical subjects

Elena Putignano

Publications and source records attributed to Elena Putignano.

3 recordsLinked to original sources

Acceleration of visual system development by environmental enrichment.

Thus far, the developmental plasticity of the visual system has been studied by altering or reducing visual experience. Here, we investigated whether a complex sensory-motor stimulation, provided by rearing animals in an enriched environment, affects visual system development. We found that raising mice in this condition causes an earlier eye opening, a precocious development of visual acuity, and an accelerated decline of white matter-induced long-term potentiation. These effects are accompanied by a precocious cAMP response element-mediated gene expression and a significant increase of BDNF protein and GAD65/67 expression in enriched pups. In addition, we showed that enriched pups experienced higher levels of licking behavior provided by adult females. Thus, rearing mice from birth in an enriched environment leads to a conspicuous acceleration of visual system development as ascertained at behavioral, electrophysiological, and molecular level.

Animals↗

Enriched environment and acceleration of visual system development.

Rearing mice from birth in an enriched environment leads to a conspicuous acceleration of visual system development appreciable at behavioral, electrophysiological and molecular level. Little is known about the possible mechanisms of action through which enriched environment affects visual system development. It has been suggested that differences in maternal behavior between enriched and non-enriched conditions could contribute to the earliest effects of enriched environment on visual development and that neurotrophins, BDNF in particular, might be involved. Here, we examined Brain Derived Neurotrophic Factor (BDNF) levels in the visual cortex during development and showed that an increase occurs in the first week of life in enriched pups compared to standard reared pups; BDNF levels at birth were equal in the two groups. This suggests a postnatal rather than a prenatal effect of environment on BDNF. A detailed analysis of maternal care behavior showed that pups raised in a condition of social and physical enrichment experienced higher levels of licking behavior and physical contact compared to standard reared pups and that enhanced levels of licking were also provided to pups in an enriched environment where no adult females other than the mother were present. Thus, different levels of maternal care in different environmental conditions could act as indirect mediator for the earliest effects of enrichment on visual system development. Some of the effects of different levels of maternal care on the offspring behavior are long lasting. We measured the visual acuity of differentially reared mice at the end of the period of visual acuity development (postnatal day 45) and at 12 months of age, using a behavioral discrimination task. We found better learning abilities and higher visual acuity in enriched compared to standard reared mice at both ages.

Aging↗

Patterned vision causes CRE-mediated gene expression in the visual cortex through PKA and ERK.

Normal visual experience during postnatal development is necessary for the maturation of visual cortical circuits and acts through molecular mechanisms that are still poorly understood. Recently, it has been shown that ERK (extracellular signal-regulated kinase) 1/2, protein kinase A (PKA), and CREB (cAMP response element-binding protein) are crucial factors for experience-dependent development of the visual cortex, but very little is known about the role of visual experience in their activation. Here, we show that visual stimulation after a brief period of dark rearing caused a transient ERK activation in the visual cortex. Visually induced ERK activation occurred primarily in excitatory neurons of layers II-III and VI and was prevented by binocular lid suture. ERK phosphorylation was strongly reduced by cortical infusion with the cAMP-PKA inhibitor Rp-8-Cl-cAMPS, thus establishing a link between PKA and ERK activation. To analyze the downstream consequences of ERK and PKA signaling, we studied the action of visual stimulation on transcription of genes controlled by CREB in transgenic mice carrying the LacZ reporter gene under the control of the CRE (cAMP response element) promoter. Visual stimulation triggered a prolonged episode of CRE-mediated gene expression in the visual cortex that was suppressed by infusion with the ERK inhibitor U0126. Cortical administration of Rp-8-Cl-cAMPS attenuated the experience-dependent activation of CRE-mediated gene transcription. These results show that ERK phosphorylation in visual cortical neurons represents a molecular readout of patterned visual stimuli and that visual activation of ERK involves the cAMP-PKA system. Finally, because CRE-mediated gene expression was totally dependent on ERK activation, we suggest that PKA action on CRE-mediated gene expression is mediated by ERK.

Anesthetics, Intravenous↗