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)
Project #
Application #
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Steinmetz, Michael A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Fu, Yu; Tucciarone, Jason M; Espinosa, J Sebastian et al. (2014) A cortical circuit for gain control by behavioral state. Cell 156:1139-52
Toyoizumi, Taro; Kaneko, Megumi; Stryker, Michael P et al. (2014) Modeling the dynamic interaction of Hebbian and homeostatic plasticity. Neuron 84:497-510
Southwell, Derek G; Nicholas, Cory R; Basbaum, Allan I et al. (2014) Interneurons from embryonic development to cell-based therapy. Science 344:1240622
Lee, A Moses; Hoy, Jennifer L; Bonci, Antonello et al. (2014) Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion. Neuron 83:455-66
Kaneko, Megumi; Xie, Yuxiang; An, Juan Ji et al. (2012) Dendritic BDNF synthesis is required for late-phase spine maturation and recovery of cortical responses following sensory deprivation. J Neurosci 32:4790-802
Niell, Cristopher M; Stryker, Michael P (2010) Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65:472-9
Sato, Masaaki; Stryker, Michael P (2010) Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a. Proc Natl Acad Sci U S A 107:5611-6
Triplett, Jason W; Owens, Melinda T; Yamada, Jena et al. (2009) Retinal input instructs alignment of visual topographic maps. Cell 139:175-85
Kaneko, Megumi; Stellwagen, David; Malenka, Robert C et al. (2008) Tumor necrosis factor-alpha mediates one component of competitive, experience-dependent plasticity in developing visual cortex. Neuron 58:673-80
Cang, Jianhua; Wang, Lupeng; Stryker, Michael P et al. (2008) Roles of ephrin-as and structured activity in the development of functional maps in the superior colliculus. J Neurosci 28:11015-23

Showing the most recent 10 out of 32 publications