Optimal functioning of the nervous system requires selective wiring of neural circuits, the precision of which is achieved through experience-dependent refinement after birth. A classical model system of the experience-dependent development is the ocular dominance plasticity in the visual system, where monocular eyelid closure in a """"""""critical period"""""""" of early life leads to a shift of cortical responses towards the non-deprived eye. Despite decades of work, it is still unknown what purpose the critical period serves during normal development, when the inputs from the two eyes are intact. In this grant, the proposed work aims to determine what cortical function is shaped by normal vision-induced plasticity during the critical period and to reveal its underlying molecular and synaptic mechanisms. First, the investigators will test whether the critical period plasticity drives the matching of binocular orientation preference during normal development. Both single unit recording and two-photon calcium imaging will be performed in the mouse visual cortex to determine the time course of binocular matching of orientation preference and its requirement of normal visual experience in the critical period. Second, with genetically or pharmacologically altered level of inhibition, which is known to shift the timing of the critical period of ocular dominance plasticity, the investigators will determine whether intracortical inhibition controls the timing of binocular matching by regulating the maturation of orientation selectivity. Intracellular whole cell recording will also be performed in vivo to reveal the spatiotemporal patterns of synaptic inhibition in mediating the binocular matching of orientation preference and in regulating the critical period timing. Finally, the receptive field structure of individual cortical neurons will be studied separately to the two eyes at different developmental stages to reveal how receptive fields change monocularly during the critical period to mediate binocular matching of orientation preference. Pharmacological experiments will also be carried out to determine if cortical activity and NMDA receptor activation are required for the binocular matching process. Together, these studies will reveal a physiological role for the critical period in normal development. Because ocular dominance plasticity and its critical period is a model system for human amblyopia and strabismus, a full understanding of cortical changes that normally take place during development will have important implications for the understanding and treatment of these diseases.
The long-term goal of our research is to reveal the function and development of precise connections between neurons in the nervous system. These studies are of great clinical importance, because many neurological and psychiatric disorders result from miswiring of synaptic connections, such as cortical blindness, seizure, and mental retardation. Our studies will thus contribute to the understanding and treatment of these disorders.
|Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron et al. (2017) Retinal origin of direction selectivity in the superior colliculus. Nat Neurosci 20:550-558|
|Levine, Jared N; Chen, Hui; Gu, Yu et al. (2017) Environmental Enrichment Rescues Binocular Matching of Orientation Preference in the Mouse Visual Cortex. J Neurosci 37:5822-5833|
|Gu, Yu; Cang, Jianhua (2016) Binocular matching of thalamocortical and intracortical circuits in the mouse visual cortex. Elife 5:|
|Levine, Jared N; Gu, Yu; Cang, Jianhua (2015) Seeing Anew through Interneuron Transplantation. Neuron 86:858-860|
|Krishnan, Keerthi; Wang, Bor-Shuen; Lu, Jiangteng et al. (2015) MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex. Proc Natl Acad Sci U S A 112:E4782-91|
|Inayat, Samsoon; Barchini, Jad; Chen, Hui et al. (2015) Neurons in the most superficial lamina of the mouse superior colliculus are highly selective for stimulus direction. J Neurosci 35:7992-8003|
|Wang, Lupeng; Liu, Mingna; Segraves, Mark A et al. (2015) Visual Experience Is Required for the Development of Eye Movement Maps in the Mouse Superior Colliculus. J Neurosci 35:12281-6|
|Chen, Hui; Zhao, Yan; Liu, Mingna et al. (2015) Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension. Invest Ophthalmol Vis Sci 56:1971-84|
|Zhao, Xinyu; Liu, Mingna; Cang, Jianhua (2014) Visual cortex modulates the magnitude but not the selectivity of looming-evoked responses in the superior colliculus of awake mice. Neuron 84:202-213|
|Sarnaik, Rashmi; Chen, Hui; Liu, Xiaorong et al. (2014) Genetic disruption of the On visual pathway affects cortical orientation selectivity and contrast sensitivity in mice. J Neurophysiol 111:2276-86|
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