Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF

Abstract

Visual deprivation such as dark rearing (DR) prolongs the critical period for ocular dominance plasticity and retards the maturation of ␥-aminobutyric acid (GABA)ergic inhibition in visual cortex. The molecular signals that mediate the effects of DR on the development of visual cortex are not well defined. To test the role of brain-derived neurotrophic factor (BDNF), we examined the effects of DR in transgenic mice in which BDNF expression in visual cortex was uncoupled from visual experience and remained elevated during DR. In dark-reared transgenic mice, visual acuity, receptive field size of visual cortical neurons, critical period for ocular dominance plasticity, and intracortical inhibition were indistinguishable from those observed in light-reared mice. Therefore, BDNF overexpression is sufficient for the development of aspects of visual cortex in the absence of visual experience. These results suggest that reduced BDNF expression contributes to retarded maturation of GABAergic inhibition and delayed development of visual cortex during visual deprivation.

Contrast gain control and cortical TrkB signaling shape visual acuity

“…Our results are interesting in the context of previous work showing that forebrain overexpression of BDNF induces an earlier rise of acuity during development 6 which does not require visual experience 13 . Possibly, a BDNF-mediated increase in synaptic strength and contrast gain explains part of this experience-independent increase in acuity in addition to the observed reduction of receptive field sizes in these animals.…”

“…In amblyopic rats receiving environmental enrichment 11 or antidepressant treatment 12 , increased BDNF expression in the cortex was seen in parallel to the restoration of visual acuity. Moreover, transgenic mice overexpressing BDNF in the forebrain show a faster rise of cortical acuity 6 even when reared in darkness 13 . Although there is a wealth of data on the involvement of BDNF and its main receptor TrkB in neuronal development 14 , synaptic efficacy 15 , -morphology 16 and -plasticity 17,18 , it has remained unknown how BDNF promotes visual acuity at the coding level and whether BDNF signaling plays a role in acuity in the mature cortex.…”

Nurturing brain plasticity: impact of environmental enrichment

“…40,41 Indeed, mice raised in EE show increased levels of the BDNF protein in their visual cortex at P7, 34,35 revealing the fact that neurotrophin BDNF is one of the crucial factors that underlie EE effects on V1 maturation. In both BDNF overexpressing mice and EE pups, higher BDNF levels were also shown to trigger the maturation of the inhibitory GABAergic system, which, by affecting receptive field development and synaptic plasticity, could determine both the accelerated maturation of VA and the decline of cortical plasticity.…”

Visual Acuity Development and Plasticity in the Absence of Sensory Experience

“…Imbalance of visual inputs between the two eyes, such as with monocular deprivation (MD), for example, shifts the spiking response of visual cortical neurons in favor of the open eye and it is accompanied by an enduring loss of visual acuity or amblyopia in the deprived eye (Wiesel and Hubel, 1963;Dews and Wiesel, 1970;Hubel and Wiesel, 1970;Movshon and Dürsteler, 1977;Blakemore et al, 1978;Dräger, 1978;Giffin and Mitchell, 1978;Olson and Freeman, 1980;Fagiolini et al, 1994;Gordon and Stryker, 1996;Daw, 1998;Kiorpes et al, 1998;Issa et al, 1999;Fagiolini and Hensch, 2000;Prusky et al, 2000). Complete removal of sensory experience by dark-rearing from birth (chronic dark rearing; CDR), affects the general maturation of several RF properties and the expression of their respective CP plasticity (Regal et al, 1976;Teller et al, 1978;Cynader and Mitchell, 1980;Mower, 1991;Fagiolini et al, 1994;Crair et al, 1998;Gianfranceschi et al, 2003). To identify the underlying molecular and cellular mechanisms of circuit refinement, the effects of different manipulations of sensory experience have been extensively studied in the rodent visual system due to its rapid postnatal development and the power of genetic manipulations (Valverde, 1971;Fagiolini et al, 1994Fagiolini et al, , 2000Gordon and Stryker, 1996;Gianfranceschi et al, 2003;Tropea et al, 2006Tropea et al, , 2010.…”

“…Complete removal of sensory experience by dark-rearing from birth (chronic dark rearing; CDR), affects the general maturation of several RF properties and the expression of their respective CP plasticity (Regal et al, 1976;Teller et al, 1978;Cynader and Mitchell, 1980;Mower, 1991;Fagiolini et al, 1994;Crair et al, 1998;Gianfranceschi et al, 2003). To identify the underlying molecular and cellular mechanisms of circuit refinement, the effects of different manipulations of sensory experience have been extensively studied in the rodent visual system due to its rapid postnatal development and the power of genetic manipulations (Valverde, 1971;Fagiolini et al, 1994Fagiolini et al, , 2000Gordon and Stryker, 1996;Gianfranceschi et al, 2003;Tropea et al, 2006Tropea et al, , 2010. Similar to higher mammals, rodent visual system develops in an experiencedependent manner (Regal et al, 1976;Teller et al, 1978;Cynader and Mitchell, 1980;Mower, 1991;Fagiolini et al, 1994;Crair et al, 1998;Gianfranceschi et al, 2003).…”