Abstract

This application seeks to investigate synaptic transmission and neuromodulation in the vertebrate retina. The focus will be at the bipolar to ganglion cell synapse. Bipolar cells have been shown in some retinas to be glutamatergic. Specifically the role of the NMDA receptor on ganglion cell activity will be investigated. In recent years the NMDA receptor has been shown to be a complex neurotransmitter receptor subtype which is modulated by extracellular glycine concentration and magnesium in relation to membrane voltage. Experiments will be carried out in the retinal slice preparation of the tiger salamander. A limited number of experiments will also be done using isolated salamander retinal cells. Whole-cell patch clamp techniques will be used to determine if the NMDA receptor on ganglion cells is modulated by extracellular substances such as magnesium or by changes in membrane voltage. The ability of NMDA to modulate action potential generation as well as synaptic input will be investigated. The role of glycine in modulating the ganglion cell NMDA receptor will be studied in addition to the regulation of glycine levels in the retina. Non-NMDA receptors elicit a transient current response due to desensitization of the receptor. The role of this transient response in shaping ganglion cell responses will be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008922-02
Application #
3266314
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-05-01
Project End
1994-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Purgert, Robert J; Lukasiewicz, Peter D (2015) Differential encoding of spatial information among retinal on cone bipolar cells. J Neurophysiol 114:1757-72
Schubert, Timm; Hoon, Mrinalini; Euler, Thomas et al. (2013) Developmental regulation and activity-dependent maintenance of GABAergic presynaptic inhibition onto rod bipolar cell axonal terminals. Neuron 78:124-37
Ichinose, Tomomi; Lukasiewicz, Peter D (2012) The mode of retinal presynaptic inhibition switches with light intensity. J Neurosci 32:4360-71
Eggers, Erika D; Lukasiewicz, Peter D (2011) Multiple pathways of inhibition shape bipolar cell responses in the retina. Vis Neurosci 28:95-108
Sagdullaev, Botir T; Eggers, Erika D; Purgert, Robert et al. (2011) Nonlinear interactions between excitatory and inhibitory retinal synapses control visual output. J Neurosci 31:15102-12
Qiu, Xudong; Goz, Didem (2010) New clues suggest distinct functional roles for M1 and M2 intrinsically photosensitive retinal ganglion cells. J Neurosci 30:1580-1
Eggers, Erika D; Lukasiewicz, Peter D (2010) Interneuron circuits tune inhibition in retinal bipolar cells. J Neurophysiol 103:25-37
Ogilvie, Judith Mosinger; Ohlemiller, Kevin K; Shah, Gul N et al. (2007) Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response. Proc Natl Acad Sci U S A 104:8514-9
Eggers, Erika D; McCall, Maureen A; Lukasiewicz, Peter D (2007) Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina. J Physiol 582:569-82
Ichinose, Tomomi; Lukasiewicz, Peter D (2007) Ambient light regulates sodium channel activity to dynamically control retinal signaling. J Neurosci 27:4756-64

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