In the developing visual system, the spatiotemporal patterns of visual inputs play an important role in shaping the connections of developing circuits. Using the developing retinotectal system of Xenopus tadpoles and a combination of in vivo whole cell recording and optical imaging techniques, we proposed to examine the development and experience-dependent refinement of visual circuits at the cellular level. In particular, we will examine the potential link between activity-dependent persistent synaptic modifications known as long-term potentiation/depression (LTP/LTD) and developmental refinement of visual circuits. The proposal consists of four parts. In PART I, we will examine the time course of synaptogenesis in the tectum, developmental changes in the synaptic function and plasticity and in the receptive field properties of tectal neurons, using a whole-cell recording method that allows the selective assessment of changes in glutamatergic and GABAergic/glycinergic inputs to the tectal neuron. The modulatory influence of GABAergic/glycinergic inputs on the development of receptive field properties will also be studied. In PART II, we will examine the effects of visual experience-evoked activity on retinotectal synapses and on the development of retinotopic map and receptive field properties. We will also determine the role of spike-timing dependent plasticity in the activity-induced refinement of retinotectal connections. In PART III, we will examine the relationship between activity-induced LTP/LTD and the structural refinement at identified retinotectal connections and the role of cooperative and competitive interactions among converging retinal inputs on the dendrite of single tectal neurons. Finally, in PART IV, we will examine the process by which visual input-induced LTP/LTD and structural modifications of retinotectal connections can be consolidated and become resistant to disruption by subsequent spontaneous spiking activity in the retinotectal system. Taken together, these in vivo studies provide unique opportunities to address several fundamental issues concerning the instructive function of sensory inputs in the refinement of developing neural connections, and are likely to yield new information relevant to our basic understanding of physiology and pathology of the developing nervous system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014979-04
Application #
7125972
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Oberdorfer, Michael
Project Start
2003-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$364,270
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Park, Hyungju; Poo, Mu-ming (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14:7-23
Shelly, Maya; Cancedda, Laura; Lim, Byung Kook et al. (2011) Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth. Neuron 71:433-46
Gong, Li-Qin; He, Ling-Jie; Dong, Zhi-Yuan et al. (2011) Postinduction requirement of NMDA receptor activation for late-phase long-term potentiation of developing retinotectal synapses in vivo. J Neurosci 31:3328-35
Cheng, Pei-Lin; Song, Ai-Hong; Wong, Yu-Hui et al. (2011) Self-amplifying autocrine actions of BDNF in axon development. Proc Natl Acad Sci U S A 108:18430-5
Lim, Byung Kook; Cho, Sung-jin; Sumbre, German et al. (2010) Region-specific contribution of ephrin-B and Wnt signaling to receptive field plasticity in developing optic tectum. Neuron 65:899-911
Lu, Hui; Cheng, Pei-Lin; Lim, Byung Kook et al. (2010) Elevated BDNF after cocaine withdrawal facilitates LTP in medial prefrontal cortex by suppressing GABA inhibition. Neuron 67:821-33
Lim, Byung Kook; Matsuda, Naoto; Poo, Mu-ming (2008) Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo. Nat Neurosci 11:160-9
Smear, Matthew C; Tao, Huizhong W; Staub, Wendy et al. (2007) Vesicular glutamate transport at a central synapse limits the acuity of visual perception in zebrafish. Neuron 53:65-77
Mu, Yangling; Poo, Mu-Ming (2006) Spike timing-dependent LTP/LTD mediates visual experience-dependent plasticity in a developing retinotectal system. Neuron 50:115-25