A major and enduring question in neuroscience is to understand the cellular mechanisms underlying the establishment and refinement of synaptic connectivity between developing sense organs and their central targets. Over the past two decades, the mammalian retinogeniculate pathway has served as an important model for demonstrating how precise patterns of connectivity are formed and the manner in which patterned activity shapes them. Prior to eye opening, aggregates of retinal ganglion cells fire in a coordinated spatiotemporal manner. These impulses travel in waves across the retina, are then transmitted to LGN and cause relay cells to strongly discharge. It is widely believed that such activity is needed for the final sculpting of adult-like retinogeniculate connections. Moreover, associative synaptic processes such as long-term potentiation (LTP) and long-term depression (LTD) are thought to represent the Hebbian substrate by which co-active inputs are maintained and less active and/or asynchronous ones are pruned. Despite the overwhelming evidence underscoring the role of activity in shaping the refinement of retinogeniculate connections, it remains to be seen whether the coordinated discharge patterns of developing retinal ganglion cells can support Hebbian modifications in synaptic strength. The primary objectives of the present proposal are to ascertain whether the intrinsic activity of developing retinal ganglion cells can support long-term changes in synaptic efficacy (potentiation and depression) in LGN and then determine whether such associative changes underlie the activity-dependent refinement of retinogeniculate connections. The synaptic responses of LGN cells are studied by utilizing an isolated brainstem preparation where the dorsal thalamus and large segments of each optic nerve remain intact. Using in vitro recording techniques, the optic nerves are electrically shocked and the synaptic responses in IGN are recorded either in the form of whole-cell intracellular responses (EPSPs and EPSCs) or extracellular riled potentials. To determine whether the synaptic responses of LGN cells are subject to long-term modification, optic nerves are shocked by delivering repetitive shocks to retinal fibers in a manner that mimics the concerted discharge patterns of retinal ganglion cells or in a way that models reduced retinal activity. Specifically, we plan to test whether associative processes like long-term potentiation or depression exist at the retinogeniculate synapse, learn whether changes in synaptic strength are linked to the stabilization of retinogeniculate connections, and to elucidate the pharmacology underlying the induction and maintenance of such plasticity.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
6R01EY012716-02
Application #
6518644
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Oberdorfer, Michael
Project Start
2001-05-01
Project End
2004-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
2
Fiscal Year
2002
Total Cost
$178,750
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Tschetter, Wayne W; Govindaiah, Gubbi; Etherington, Ian M et al. (2018) Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling. J Neurosci 38:4531-4542
Kerschensteiner, Daniel; Guido, William (2017) Visual thalamus, ""it's complicated"". Vis Neurosci 34:E018
Kerschensteiner, Daniel; Guido, William (2017) Organization of the dorsal lateral geniculate nucleus in the mouse. Vis Neurosci 34:E008
Goldberg, Jeffrey L; Guido, William; Agi Workshop Participants (2016) Report on the National Eye Institute Audacious Goals Initiative: Regenerating the Optic Nerve. Invest Ophthalmol Vis Sci 57:1271-5
Bickford, Martha E; Zhou, Na; Krahe, Thomas E et al. (2015) Retinal and Tectal ""Driver-Like"" Inputs Converge in the Shell of the Mouse Dorsal Lateral Geniculate Nucleus. J Neurosci 35:10523-34
Dilger, Emily K; Krahe, Thomas E; Morhardt, Duncan R et al. (2015) Absence of plateau potentials in dLGN cells leads to a breakdown in retinogeniculate refinement. J Neurosci 35:3652-62
El-Danaf, Rana N; Krahe, Thomas E; Dilger, Emily K et al. (2015) Developmental remodeling of relay cells in the dorsal lateral geniculate nucleus in the absence of retinal input. Neural Dev 10:19
Hammer, Sarah; Carrillo, Gabriela L; Govindaiah, Gubbi et al. (2014) Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamus. Neural Dev 9:16
Brooks, Justin M; Su, Jianmin; Levy, Carl et al. (2013) A molecular mechanism regulating the timing of corticogeniculate innervation. Cell Rep 5:573-81
Chen, Shih-Kuo; Chew, Kylie S; McNeill, David S et al. (2013) Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron 77:503-15

Showing the most recent 10 out of 29 publications