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.
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.
|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