BDNF Regulates the Maturation of Inhibition and the Critical Period of Plasticity in Mouse Visual Cortex

Abstract

Maturation of the visual cortex is influenced by visual experience during an early postnatal period. The factors that regulate such a critical period remain unclear. We examined the maturation and plasticity of the visual cortex in transgenic mice in which the postnatal rise of brain-derived neurotrophic factor (BDNF) was accelerated. In these mice, the maturation of GABAergic innervation and inhibition was accelerated. Furthermore, the age-dependent decline of cortical long-term potentiation induced by white matter stimulation, a form of synaptic plasticity sensitive to cortical inhibition, occurred earlier. Finally, transgenic mice showed a precocious development of visual acuity and an earlier termination of the critical period for ocular dominance plasticity. We propose that BDNF promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity.

Food restriction enhances visual cortex plasticity in adulthood

“…Maturation of inhibition has been proposed to reduce synaptic plasticity in the visual cortex by acting as a gate, which filters the level and pattern of activity that layer IV, the major thalamo-recipient layer, is able to relay to supragranular layers [19][20][21] . Indeed, it has been demonstrated that the induction of long-term potentiation (LTP) in the layer II-III of the cortex through stimulation of the white matter (WM-LTP) declines with age and contrasting inhibition by acute application of GABA receptor antagonists on visual cortical slices in adulthood enhances WM-LTP 22 .…”

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

“…The magnitudes of observed expression changes were more prominent in the qPCR experiment than those reported by the GeneChips, confirming previous reports that RMA analysis may underestimate the expression differences in microarray experiments. 20,24 BDNF is required for maintenance of SST-NPY interneuronal phenotype in the frontal cortex Brain-derived neurotrophic factor is believed to be critical for the development of cortical interneurons, 4,6,[33][34][35] but the specificity of BDNF action for specific subclasses of interneurons is not known. Our previously published study suggested that the PARV containing interneuronal class is not affected in either one of these BDNF-ablated mice and that the overall GABA-ergic phenotype of the interneurons, judged by presence of GAD1 transcript levels, is preserved.…”

“…For example, the development of certain phenotypic features of cortical GABA neurons requires BDNF. [2][3][4][5][6] In addition, BDNF is produced and released in an activity-dependent fashion by pyramidal neurons, a major target of GABA neurons. Together, these data suggest that BDNF is a target-derived trophic factor for GABA interneurons.…”

Contrast gain control and cortical TrkB signaling shape visual acuity

“…During development, acuity and BDNF levels rise 6 , while both slowly decrease with age 4,7 . This relationship between BDNF and acuity also holds for experimentally induced amblyopia.…”

“…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.…”