Novel players in activity-dependent neuronal plasticity in the visual cortex

Abstract

Activity-dependent neuronal plasticity is an essential process for the brain to change in response to its surroundings, both during development and in adulthood. This plasticity underlies every event of learning and memory that is crucial to our daily lives. Despite decades of research, we have yet to understand how the brain coordinates plasticity mechanisms to adapt to constantly changing environmental conditions. Ocular dominance plasticity is a model of activity-dependent plasticity in the visual cortex that has been extensively used to investigate the mechanisms underlying neuronal plasticity. Identifying the specific proteins involved in these mechanisms is the first step to finding viable therapeutic targets in disorders like Fragile X syndrome, autism spectrum disorder and major depressive disorder, where plasticity is disrupted. I used in vivo electrophysiology as well as microscopy and biochemistry techniques to identify novel players in activity-dependent plasticity in the visual cortex. My results reveal that the astrocyte-secreted, trans-synaptic bridging protein hevin, as well as three nuclear transcription factors CREB, SRF and MEF2, are indispensable to ocular dominance plasticity. Additionally, I found that the activation of CREB via phosphorylation at serine 142 and 143 is required for ocular dominance plasticity. These findings further our knowledge about the regulation of neuronal plasticity by astrocytes outside the neuron, as well as the regulation of plasticity from within the nuclei of the neurons themselves.