Visual experience can produce long-lasting changes in the function of the primary visual cortex (V1), especially during a critical period early in postnatal life. There are two forms of functional plasticity that occur at V1 synapses: one that is input-specific and the other that is global across all synapses. The former is thought to be critical for the formation and/or maintenance of proper connectivity, while the latter provides homeostasis and stability. We found that a few days of binocular visual deprivation (i.e. dark-rearing) following normal development globally increases the strength of excitatory synaptic transmission in the superficial layers of V1, which was rapidly reversed by re-exposure to light. These changes followed the rules of a homeostatic plasticity mechanism termed synaptic scaling. We found that AMPA receptor (AMPAR) regulation plays a central role in the visual experience-induced homeostatic synaptic changes. Specifically, we observed an increase in phosphorylation of AMPAR subunit GluR1 (or GluA1) and appearance of Ca2+permeable AMPARs (CP-AMPARs) at synapses, which correlated with the increase in excitatory synaptic strength observed in dark-reared mice. On the other hand, an immediate early gene product Arc (activity-regulated cytoskeletal protein) was involved in scaling down excitatory synapses with light exposure. Our results provide a molecular framework to understand homeostatic plasticity at excitatory synapses in V1. However, there are several questions that remain unanswered: The molecular events that trigger synaptic scaling, whether inhibitory synapses undergo homeostatic synaptic plasticity, and how synaptic scaling interacts with input-specific plasticity are unknown. We will attempt to investigate these in the current proposal. Because of the central role AMPAR regulation and Arc play in visual experience-induced homeostatic synaptic plasticity, we will examine their upstream signals, specifically signaling through metabotropic glutamate receptors (mGluRs), to determine the molecular events that trigger this form of plasticity (Aim 1). We recently found that a brief dark-rearing triggers global changes in inhibitory synaptic function, which was independent of the mechanisms recruited for excitatory synapse regulation. Hence, we will examine the mechanisms of homeostatic regulation of inhibitory synapses in V1 (Aim 2). Global homeostatic synaptic changes are expected to alter the rules of input-specific synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). In line with this, we found that visual deprivation reveals a novel NMDAR-independent form of synaptic plasticity, which will be investigated in this proposal (Aim 3). Understanding how excitatory and inhibitory synaptic function is globally adjusted by visual experience is critical, because it impacts the rules of input-specific synaptic modification. Our finding that homeostatic synaptic plasticity in the superficial layers of V1 can result from a few days of visual deprivation, even in adults, suggest that elucidating the underlying molecular mechanisms will provide valuable tools to either enhance or restrict plasticity in V1.
Loss of vision early in life causes blindness even if the optics of the eye is restored later, because it permanently changes the function of the brain. Therefore, understanding how the brain function changes by visual experience is critical in developing ways to recover vision.
|Lee, Hey-Kyoung; Whitt, Jessica L (2015) Cross-modal synaptic plasticity in adult primary sensory cortices. Curr Opin Neurobiol 35:119-26|
|Whitt, Jessica L; Petrus, Emily; Lee, Hey-Kyoung (2014) Experience-dependent homeostatic synaptic plasticity in neocortex. Neuropharmacology 78:45-54|
|Gao, Ming; Maynard, Kristen R; Chokshi, Varun et al. (2014) Rebound potentiation of inhibition in juvenile visual cortex requires vision-induced BDNF expression. J Neurosci 34:10770-9|
|Petrus, Emily; Lee, Hey-Kyoung (2014) BACE1 is necessary for experience-dependent homeostatic synaptic plasticity in visual cortex. Neural Plast 2014:128631|
|Huang, Shiyong; Rozas, Carlos; TreviÃ±o, Mario et al. (2014) Associative Hebbian synaptic plasticity in primate visual cortex. J Neurosci 34:7575-9|
|Ikrar, Taruna; Guo, Nannan; He, Kaiwen et al. (2013) Adult neurogenesis modifies excitability of the dentate gyrus. Front Neural Circuits 7:204|
|Guo, Yatu; Huang, Shiyong; de Pasquale, Roberto et al. (2012) Dark exposure extends the integration window for spike-timing-dependent plasticity. J Neurosci 32:15027-35|
|Lee, Hey-Kyoung (2012) Ca-permeable AMPA receptors in homeostatic synaptic plasticity. Front Mol Neurosci 5:17|
|He, Kaiwen; Petrus, Emily; Gammon, Nicholas et al. (2012) Distinct sensory requirements for unimodal and cross-modal homeostatic synaptic plasticity. J Neurosci 32:8469-74|
|Qian, Hai; Matt, Lucas; Zhang, Mingxu et al. (2012) Ã½Ã½2-Adrenergic receptor supports prolonged theta tetanus-induced LTP. J Neurophysiol 107:2703-12|
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