CELLULAR MECHANISMS UNDERLYING HOMEOSTATIC AND CROSS-MODAL PLASTICITY IN MOUSE PRIMARY VISUAL CORTEX

The brain has an essential ability to modify and reorganize synaptic connections according to experience. Sensory experience, in particular, is required for the formation of cortical circuits during early postnatal development and for their regulation throughout life. Synaptic connections are modified according to experience through two mechanisms, synapse-specific (Hebbian) and global (homeostatic) plasticity, which must work in harmony to achieve optimal processing. Sensory loss causes brain-wide adaptations that engage both types of synaptic plasticity. In the deprived cortex, homeostatic mechanisms of plasticity regulate synaptic function after prolonged periods of sensory loss, whereas spared cortical areas undergo compensatory cross-modal synaptic plasticity. We have utilized rodent primary visual cortex (V1) to investigate the mechanisms that mediate these compensatory changes after sensory loss. Here, we demonstrate the indispensable role of NMDARs in both types of plasticity. First, we provide evidence for the requirement of NMDARs in homeostatic synaptic plasticity after uni-modal sensory loss (dark exposure). In parallel, we induced cross-modal plasticity in V1 of adult mice by deafening animals older than 3 months (P90-120). Inspired by previous work showing synaptic strengthening in the feedforward thalamic input after cross-modal sensory deprivation (Petrus et al., 2014), we investigated the molecular mechanisms underlying this post- critical period plasticity. We show that cross-modal TC plasticity in the adult brain is driven mainly by the resurgence of NMDAR-dependent LTP at TC synapses, with no modulation on feedforward inhibition. Moreover, we demonstrate in vivo functional consequences of deafening on V1 by using ocular dominance plasticity (ODP) as a model. Briefly, we show that deafening accelerates ODP in adult V1 by promoting open-eye potentiation during monocular deprivation (MD). Taken together, our results indicate that both uni-modal and cross-modal plasticity rely on similar molecular mechanisms to adapt to changes in the environment. They also provide insights into the brain’s ability to adapt beyond the critical period and suggest cross-modal sensory deprivation may be an effective way to re-engage plasticity in the adult brain