Molecular mechanisms at the basis of plasticity in the developing visual cortex: epigenetic processes and gene programs

Abstract

Neuronal circuitries in the mammalian visual system change as a function of experience. Sensory experience modifies neuronal networks connectivity via the activation of different physiological processes such as excitatory/inhibitory synaptic transmission, neurotrophins, and signaling of extracellular matrix molecules. Long-lasting phenomena of plasticity occur when intracellular signal transduction pathways promote epigenetic alterations of chromatin structure that regulate the induction of transcription factors that in turn drive the expression of downstream targets, the products of which then work via the activation of structural and functional mechanisms that modify synaptic connectivity. Here, we review recent findings in the field of visual cortical plasticity while focusing on how physiological mechanisms associated with experience promote structural changes that determine functional modifications of neural circuitries in V1. We revise the role of microRNAs as molecular transducers of environmental stimuli and the role of immediate early genes that control gene expression programs underlying plasticity in the developing visual cortex.

Keywords: GABAergic interneurons; Npas4; OTX2; chromatin remodeling; epigenetics; extracellular matrix; microRNAs; plasticity; visual cortex.

Figure 1

A two-threshold model for OTX2 in the regulation of visual cortical plasticity during early life. Visual experience drives the initial incorporation of the OTX2 protein into Pv+ GABAergic cells. This results in the initial functional maturation of inhibition and the CP onset. As development proceeds, PNNs condense around inhibitory interneurons, leading to higher levels of OTX2 accumulation that in turn promote inhibition and eventually reduce plasticity while causing neuronal circuitries consolidation and stability in V1. OTX2 is synthesized, secreted and maintained in Pv+ GABAergic cells in the mature brain.

Figure 2

Model for the vision responsive epigenetic regulation of miR132. Mir132 is produced by a bicistronic transcript containing also miR212 (primary-miR212/132). Visual experience enhances both the primary miR212/132 and mature miR132 transcript. Basal mature miR212 levels are much lower than miR132 levels due to a different processing and stability. Its regulation by visual experience has not been investigated. The miR212/132 gene is reported in dark green. Mature miR212 and miR132 sequence are reported in light green.