This application proposes neurophysiological studies to elucidate the mechanisms by which patterns of neural activity may guide or affect the development and plasticity of the mammalian visual cortex. Our previous research has shown that spontaneous neural activity in the visual system is require for the development of ocular dominance columns in the visual cortex, an event that begins in utero in higher primates. Our more recent experiments have demonstrated a similar requirement for neural activity for the development of eye-specific laminae in the lateral geniculate nucleus; this process is essentially complete before the time of birth even in our feline model. The findings suggest that abnormalities in the spontaneous patterns of neural activity in utero may be a hitherto unsuspected cause of birth defects. In addition, and understanding in detail of the mechanisms of plasticity in the developing visual system should provide a rational basis to therapy for ambloyopia, a clinical disorder affecting as many as 2% of all children.
The specific aim of this proposal is to explore in detail the synaptic plasticity in the developing visual cortex produced by pharmacologically inhibiting the postsynaptic cortical cells. Our recent work has demonstrated that infusion of the GABA-A agonist muscimol into kitten visual cortex causes plasticity in favor of the less-active input when one eye is deprived of vision. The implications of this unprecedented phenomenon will be explored by determining the necessary does of a variety of inhibitory Agents, be delineating the period of susceptibility to the effects of these agents on cortical plasticity, by making quantitative measurements of visual responses following such plasticity, by conducting longer-term physiological experiments and anatomical studies of transneuronally labelled ocular dominance columns, and by pharmacological studies of effects on various receptor types.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY002874-10A1
Application #
3257169
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1978-12-01
Project End
1994-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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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