Orderly neural circuits underlie processing of information in the nervous system: our perceptions, decisions and behaviors. A main goal of neurobiology is to understand how the circuits form. We use the retina to address this issue. Distinct types of retinal ganglion cells respond to different visual features, based on which inputs they receive from retinal interneurons. Several types are direction selective, responding best to objects moving in a particular direction. The mammalian retina contains at least 3 types of direction selective ganglion cells (DSGCs). However, the lack of molecular markers to selectively identify DSGCs has impeded analysis of their development, synaptic inputs in the retina, and targets in the brain. We have now found markers for 3 types of DSGCs and developed transgenic approaches to label each type in vivo. This method allows us to elucidate molecular mechanisms that regulate differentiation of these neurons, and to trace the neuronal circuits that initiate responses to moving objects.
In specific aims 1 -3, we will characterize mice in which each DSGC type is specifically labeled. We will analyze the morphological and functional development of each DSGC type, and seek roles of the subtype specific genes (an adhesion molecule, JAM-B and two secreted molecules, FSTL4 and SPIG1/FSTL5) in these processes.
In specific aim 4, we will use transsynaptic tracers to define the connections of each DSGC type. Finally (specific aim 5), we will seek new molecules that regulate diverse aspects of DSGC development. Together, these studies will provide novel insights into the cellular basis of visual processing. Following the mentored period in the Center for Brain Science at Harvard University, I will start my own lab as an independent investigator at an academic institution. My long-term goal is to study how neural circuits are formed and modified by experience. I hope that my work will provide insights in studying how neural circuit fails in psychiatric diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Career Transition Award (K99)
Project #
1K99EY019355-01
Application #
7569088
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Greenwell, Thomas
Project Start
2009-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$90,001
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
De la Huerta, Irina; Kim, In-Jung; Voinescu, P Emanuela et al. (2012) Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors. Proc Natl Acad Sci U S A 109:17663-8
Zhang, Yifeng; Kim, In-Jung; Sanes, Joshua R et al. (2012) The most numerous ganglion cell type of the mouse retina is a selective feature detector. Proc Natl Acad Sci U S A 109:E2391-8
Kay, Jeremy N; De la Huerta, Irina; Kim, In-Jung et al. (2011) Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections. J Neurosci 31:7753-62
Hong, Y Kate; Kim, In-Jung; Sanes, Joshua R (2011) Stereotyped axonal arbors of retinal ganglion cell subsets in the mouse superior colliculus. J Comp Neurol 519:1691-711
Kim, In-Jung; Zhang, Yifeng; Meister, Markus et al. (2010) Laminar restriction of retinal ganglion cell dendrites and axons: subtype-specific developmental patterns revealed with transgenic markers. J Neurosci 30:1452-62