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TARPγ2 Is Required for Normal AMPA Receptor Expression and Function in Direction-Selective Circuits of the Mammalian
Todd Stincic1, Jacqueline Gayet-Primo2,3,1, W Rowland Taylor2,3,1
1Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239.
Eneuro
|July 25, 2023
Summary
Transmembrane AMPA receptor regulatory proteins gamma2 (TARPγ2) are crucial for synaptic expression of AMPA receptors (AMPARs) in the retina. Loss of TARPγ2 in stargazer mice reduces AMPARs and alters retinal circuit function.
Area of Science:
- Neuroscience
- Retinal Physiology
- Molecular Biology
Background:
- AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the retina.
- Auxiliary subunits, including TARPs, modulate AMPAR function, but retinal TARP composition is unknown.
- Starburst amacrine cells (SACs) are key interneurons in retinal processing.
Purpose of the Study:
- To identify TARP subunits in the retina and their role in AMPAR regulation.
- To investigate the function of TARPγ2 (stargazin) in retinal synaptic transmission.
- To analyze the impact of TARPγ2 deficiency on retinal circuit function and visual processing.
Main Methods:
- Immunohistochemistry in mouse, rabbit, macaque, and human retina.
- Transcriptomic analysis of mouse and human SACs.
- Electrophysiology on retinal slices from stargazer (TARPγ2 knockout) mice.
- Analysis of light-evoked responses in ON-SACs and direction-selective ganglion cells.
Main Results:
- TARPγ2 is localized in the synaptic layers of mammalian retinas, particularly where SACs ramify.
- TARPγ2 deficiency in stargazer mice significantly reduces synaptic GluA2, GluA3, and GluA4 expression.
- ON-SACs in stargazer mice exhibit smaller AMPAR-mediated EPSCs and altered GABAergic input.
- Direction-selective ganglion cells show reduced surround inhibition in stargazer mice.
Conclusions:
- TARPγ2 is essential for the synaptic expression of specific AMPAR subunits (GluA2, GluA3, GluA4) in the inner retina.
- TARPγ2 deficiency impairs retinal circuit function, affecting SACs and visual spatial tuning.
- The residual AMPAR expression in stargazer mutants suggests potential compensatory roles for other TARP subunits.
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