Sensory experience is required for the development of the visual system, however the direct effects of visual experience on the development of the neural circuits in visual centers have been difficult to determine. Development of neural circuits requires that neurons extend axons and dendrites into regions of the brain where they then form and maintain synaptic connections. In order to understand mechanisms controlling circuit development, it is essential to determine the mechanisms that control both the structural development of neurons and the formation of synaptic connections. The primary goal of the experiments in this proposal is to determine the activity-dependent mechanisms that govern the formation of visual system circuits. We address this question by studying the mechanisms that control the development of synaptic connections and neuronal structure in the retinotectal system of Xenopus, using imaging, electrophysiology and molecular biology methods. During the last funding period, we found that a relatively brief period of visual stimulation leads to a significant increase in growth of dendritic arbors of neurons in the optic tectum and that the increased growth of the optic tectal neurons requires glutamatergic synaptic transmission. We now have the unique opportunity to determine direct consequences of sensory experience on the structural and functional development of the visual system. We will express fluorescent proteins in presynaptic retinal axons and postsynaptic optic tectal neurons which allow us to visualize the development of neuronal structures and synapse formation in the intact brain. We propose to determine how visual stimulation and activation of postsynaptic glutamate receptors regulates growth of presynaptic retinal axons, tectal cell dendrites and formation of synaptic connections from the eye into the brain. In addition to addressing fundamental questions regarding mechanisms of synaptogenesis and stabilization, we will determine the effects of visual stimulation, synaptic transmission and glutamate receptor function on visual system development.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Steinmetz, Michael A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cold Spring Harbor Laboratory
Cold Spring Harbor
United States
Zip Code
He, Hai-Yan; Shen, Wanhua; Zheng, Lijun et al. (2018) Excitatory synaptic dysfunction cell-autonomously decreases inhibitory inputs and disrupts structural and functional plasticity. Nat Commun 9:2893
Liu, Han-Hsuan; McClatchy, Daniel B; Schiapparelli, Lucio et al. (2018) Role of the visual experience-dependent nascent proteome in neuronal plasticity. Elife 7:
Gambrill, Abigail C; Faulkner, Regina L; McKeown, Caroline R et al. (2018) Enhanced visual experience rehabilitates the injured brain in Xenopus tadpoles in an NMDAR-dependent manner. J Neurophysiol :
Gambrill, Abigail C; Faulkner, Regina L; Cline, Hollis T (2018) Direct intertectal inputs are an integral component of the bilateral sensorimotor circuit for behavior in Xenopus tadpoles. J Neurophysiol 119:1947-1961
McKeown, C R; Thompson, C K; Cline, H T (2017) Reversible developmental stasis in response to nutrient availability in the Xenopus laevis central nervous system. J Exp Biol 220:358-368
Lau, Melissa; Li, Jianli; Cline, Hollis T (2017) In Vivo Analysis of the Neurovascular Niche in the Developing Xenopus Brain. eNeuro 4:
Pratt, Kara G; Hiramoto, Masaki; Cline, Hollis T (2016) An Evolutionarily Conserved Mechanism for Activity-Dependent Visual Circuit Development. Front Neural Circuits 10:79
He, Hai-Yan; Shen, Wanhua; Hiramoto, Masaki et al. (2016) Experience-Dependent Bimodal Plasticity of Inhibitory Neurons in Early Development. Neuron 90:1203-1214
Thompson, Christopher K; Cline, Hollis T (2016) Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation, and Dendritic Arbor Elaboration in the Tadpole Visual System. J Neurosci 36:10356-10375
Truszkowski, Torrey L S; James, Eric J; Hasan, Mashfiq et al. (2016) Fragile X mental retardation protein knockdown in the developing Xenopus tadpole optic tectum results in enhanced feedforward inhibition and behavioral deficits. Neural Dev 11:14

Showing the most recent 10 out of 39 publications