» Articles » PMID: 23911793

Molecular Mechanisms Underlying Activity-dependent AMPA Receptor Cycling in Retinal Ganglion Cells

Overview
Date 2013 Aug 6
PMID 23911793
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

On retinal ganglion cells (RGCs) transmit light encoded information to the brain and receive excitatory input from On cone bipolar cells (CBPs). The synaptic CBP input onto On RGCs is mediated by AMPA-type glutamate receptors (AMPARs) that include both those lacking a GluA2 subunit, and are therefore permeable to Ca(2+), and those that possess at least one GluA2 subunit and are Ca(2+)-impermeable. We have previously demonstrated in electrophysiological studies that periods of low synaptic activity, brought about by housing animals in darkness, enhance the proportion of GluA2-lacking AMPARs at the On CBP-On RGC synapse by mobilizing surface GluA2 containing receptors into a receptor pool that rapidly cycles in and out of the membrane. AMPAR cycling induction by reduced synaptic activity takes several hours. This delay suggests that changes in expression of proteins which regulate AMPAR trafficking may mediate the altered mobility of GluA2 AMPARs in RGCs. In this study, we test the hypothesis that AMPAR trafficking proteins couple synaptic activity to AMPAR cycling in RGCs. Immunocytochemical and biochemical analyses confirmed that darkness decreases surface GluA2 in RGCs and changed the expression levels of three proteins associated with GluA2 trafficking. GRIP was decreased, while PICK1 and Arc were increased. Knockdown of GRIP with siRNA elevated constitutive AMPAR cycling, mimicking effects of reduced synaptic activity, while knockdown of PICK1 and Arc blocked increases in constitutive GluA2 trafficking. Our results support a role for correlated, activity-driven changes in multiple AMPAR trafficking proteins that modulate GluA2 cycling which can in turn affect synaptic AMPAR composition in RGCs.

Citing Articles

Light-Modulated Circadian Synaptic Plasticity in the Somatosensory Cortex: Link to Locomotor Activity.

Jasinska M, Jasek-Gajda E, Ziaja M, Litwin J, Lis G, Pyza E Int J Mol Sci. 2024; 25(23).

PMID: 39684579 PMC: 11641775. DOI: 10.3390/ijms252312870.


A circuit motif for color in the human foveal retina.

Kim Y, Packer O, Dacey D Proc Natl Acad Sci U S A. 2024; 121(36):e2405138121.

PMID: 39190352 PMC: 11388358. DOI: 10.1073/pnas.2405138121.


Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration.

Boccuni I, Fairless R Life (Basel). 2022; 12(5).

PMID: 35629305 PMC: 9147752. DOI: 10.3390/life12050638.


Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues.

Ang G, Brown L, Tam S, Davies K, Foster R, Harrison P Transl Psychiatry. 2021; 11(1):588.

PMID: 34782594 PMC: 8593011. DOI: 10.1038/s41398-021-01690-3.


Expression of GluA2-containing calcium-impermeable AMPA receptors on dopaminergic amacrine cells in the mouse retina.

Liu L, Alessio E, Spix N, Zhang D Mol Vis. 2019; 25:780-790.

PMID: 31819340 PMC: 6882663.


References
1.
Hill M, Froc D, Fox C, Gorzalka B, Christie B . Prolonged cannabinoid treatment results in spatial working memory deficits and impaired long-term potentiation in the CA1 region of the hippocampus in vivo. Eur J Neurosci. 2004; 20(3):859-63. DOI: 10.1111/j.1460-9568.2004.03522.x. View

2.
Braithwaite S, Xia H, Malenka R . Differential roles for NSF and GRIP/ABP in AMPA receptor cycling. Proc Natl Acad Sci U S A. 2002; 99(10):7096-101. PMC: 124534. DOI: 10.1073/pnas.102156099. View

3.
Clem R, Barth A . Pathway-specific trafficking of native AMPARs by in vivo experience. Neuron. 2006; 49(5):663-70. DOI: 10.1016/j.neuron.2006.01.019. View

4.
Sutton M, Ito H, Cressy P, Kempf C, Woo J, Schuman E . Miniature neurotransmission stabilizes synaptic function via tonic suppression of local dendritic protein synthesis. Cell. 2006; 125(4):785-99. DOI: 10.1016/j.cell.2006.03.040. View

5.
Demb J . Functional circuitry of visual adaptation in the retina. J Physiol. 2008; 586(18):4377-84. PMC: 2614018. DOI: 10.1113/jphysiol.2008.156638. View