We have previously characterized the highly specific responses of neurons in the primary visual cortex (V1) of anesthetized mice and found those properties to be preserved in alert mice. Recordings in V1 of alert adult mice revealed a dramatic, cortical-specific enhancement of visual responses by locomotion constituting a change in the gain of cortical responses, while preserving their specificity, resembling but much greater than the gain change produced by focal attention in higher visual areas of the primate. This proposal seeks to determine whether these enhanced responses can facilitate adult recovery of visual function in a mouse model of amblyopia, as suggested by preliminary findings, and if so by what means. It also seeks to determine the neural circuit substrates for the enhancement of visual responses by locomotion. . Understanding this circuit may guide therapeutic efforts directed to enhancing plasticity after trauma or injury.

Public Health Relevance

This proposal starts from an appreciation of the differences between the dramatic capacity of the young mammalian brain to alter its connections and function as a result of experience and the slower and more limited plasticity in adult life, and it seeks to enhance adult plasticity. We have previously found that visual cortical responses are increased during locomotion. We will investigate the neural circuits that produce this enhancement of neural activity and will use it to increase adult plasticity. Understanding the processes responsible for brain plasticity in adult life will guide the restoration of normal functon after visual deprivation, injury, or other neurological disorders involving aberrant neuronal connections and processing, such as generalized seizures, autism and mental retardation.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Greenwell, Thomas
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University of California San Francisco
Schools of Medicine
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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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