Many aspects of the later stages of neural development are guided by neuronal activity. Guidance is given both by intrinsic patterns of activity, before and after birth, and by activity resulting from experience after birth. Theoretical studies will address the role of activity-dependent mechanisms in the development of the mammalian primary visual cortex. Such cortical mechanisms appear to play an important role in many aspects of human health, including visual disorders such as strabismus and amblyopia, as well as recovery and reorganization of visual function after retinal lesions. The theoretical studies will address the following specific questions in the development of the primary visual cortex: (1) The relationships that may develop between the maps of retinotopy, ocular dominance, orientation, disparity, and other cortical receptive field properties such as preferred spatial frequency and spatial phase, and the relationships among these properties that develop in individual receptive fields, when inputs of four types (ON-center and OFF-center from the left and right eyes) compete to innervate a two-dimensional cortical layer representing layer 4 of primary visual cortex; (2) The relationships that develop between the receptive fields of excitatory and inhibitory neurons when both types of neurons are included, with realistic connectivity, in the model of the layer 4 circuit; (3) The effects on these relationships of simultaneous plasticity of intracortical, as well as, feedforward synapses, and of more realistic models of synaptic plasticity and competition motivated by recent experimental work. In all of these studies, the goal will be to characterize the different possible developmental outcomes that may result under activity-dependent, correlation-based mechanisms of synaptic plasticity, and to determine the experimentally measurable and manipulable factors that will determine the actual outcome, if such mechanisms underlie development. This will provide a basis for experimental tests of the hypothesis that such mechanisms underlie the studied phenomena, and ultimately for improvements of related human health problems, such as strabismus, amblyopia, and retinal lesions.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Cognitive Functional Neuroscience Review Committee (CFN)
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Broman, Sarah H
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University of California San Francisco
Schools of Medicine
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Liu, Liu D; Miller, Kenneth D; Pack, Christopher C (2018) A Unifying Motif for Spatial and Directional Surround Suppression. J Neurosci 38:989-999
Zhang, Wujie; Falkner, Annegret L; Krishna, B Suresh et al. (2017) Coupling between One-Dimensional Networks Reconciles Conflicting Dynamics in LIP and Reveals Its Recurrent Circuitry. Neuron 93:221-234
Miller, Kenneth D (2016) Canonical computations of cerebral cortex. Curr Opin Neurobiol 37:75-84
Ahmadian, Yashar; Fumarola, Francesco; Miller, Kenneth D (2015) Properties of networks with partially structured and partially random connectivity. Phys Rev E Stat Nonlin Soft Matter Phys 91:012820
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Rubin, Daniel B; Van Hooser, Stephen D; Miller, Kenneth D (2015) The stabilized supralinear network: a unifying circuit motif underlying multi-input integration in sensory cortex. Neuron 85:402-17
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Toyoizumi, Taro; Miyamoto, Hiroyuki; Yazaki-Sugiyama, Yoko et al. (2013) A theory of the transition to critical period plasticity: inhibition selectively suppresses spontaneous activity. Neuron 80:51-63

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