This proposal seeks to discover the intercellular signaling and specific neural circuit substrates of the loss and recovery of binocular responses in the visual cortex during the critical period of susceptibility to the effects of monocular visual deprivation. It also seeks to understand the differences between the high degree neural plasticity at the height of the critical period and reduced plasticity in the adult visual cortex. The methods to be used are efficient means of measuring visual responses and neural circuits longitudinally in individual mice, including transcranial intrinsic signal optical imaging, extracellular microelectrode recording, 2-photon laser scanning microscopy for longitudinal anatomical studies in vivo, and 2-photon laser scanning of multiple neurons bulk-filled with calcium indicators. The time course of visual cortical plasticity in response to monocular visual deprivation and recovery at the peak of the critical period consists of distinct temporal phases. Our preliminary results show these phases to be distinct in the molecular signals that operate in each phase, so that mice mutant in specific signaling pathways are deficient in only one of the three phases. We will determine in which cells of the upper cortical layers these mechanisms influence plasticity, and how these signaling pathways and neural plasticity in response to them change in adulthood.

Public Health Relevance

The long term goal of the proposed research is to understand the cellular mechanisms and changes in the circuitry of the visual cortex that are responsible for the loss of influence of the deprived eye in experimental models of amblyopia, and to determine what is the potential for recovery. Much of the basic science in this field has concentrated on animal models of deprivation amblyopia, of which there are many, in the hope that an understanding of the neural signaling and circuit bases of plasticity would enlighten further attempts at prevention and treatment in human patients. This proposal, by identifying mechanisms that operate in different phases of plasticity and by identifying the origins of the difference between the repair potential of juvenile and visual adult cortex, should be valuable in guiding future attempts at therapy for visual cortical abnormalities.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Steinmetz, Michael A
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Dyballa, Luciano; Hoseini, Mahmood S; Dadarlat, Maria C et al. (2018) Flow stimuli reveal ecologically appropriate responses in mouse visual cortex. Proc Natl Acad Sci U S A 115:11304-11309
Stryker, Michael P; Löwel, Siegrid (2018) Amblyopia: New molecular/pharmacological and environmental approaches. Vis Neurosci 35:E018
Kaneko, Megumi; Stryker, Michael P (2017) Homeostatic plasticity mechanisms in mouse V1. Philos Trans R Soc Lond B Biol Sci 372:
Fox, Kevin; Stryker, Michael (2017) Integrating Hebbian and homeostatic plasticity: introduction. Philos Trans R Soc Lond B Biol Sci 372:
Keck, Tara; Toyoizumi, Taro; Chen, Lu et al. (2017) Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions. Philos Trans R Soc Lond B Biol Sci 372:
Dadarlat, Maria C; Stryker, Michael P (2017) Locomotion Enhances Neural Encoding of Visual Stimuli in Mouse V1. J Neurosci 37:3764-3775
Kaneko, Megumi; Fu, Yu; Stryker, Michael P (2017) Locomotion Induces Stimulus-Specific Response Enhancement in Adult Visual Cortex. J Neurosci 37:3532-3543
Larimer, Phillip; Spatazza, Julien; Espinosa, Juan Sebastian et al. (2016) Caudal Ganglionic Eminence Precursor Transplants Disperse and Integrate as Lineage-Specific Interneurons but Do Not Induce Cortical Plasticity. Cell Rep 16:1391-1404
Owens, Melinda T; Feldheim, David A; Stryker, Michael P et al. (2015) Stochastic Interaction between Neural Activity and Molecular Cues in the Formation of Topographic Maps. Neuron 87:1261-1273
Fu, Yu; Kaneko, Megumi; Tang, Yunshuo et al. (2015) A cortical disinhibitory circuit for enhancing adult plasticity. Elife 4:e05558

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