Molecular mechanisms underlying activity-dependent AMPA receptor cycling in retinal ganglion cells

Tanya M. Casimiro, Scott Nawy, Reed C. Carroll

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 Ca2+, and those that possess at least one GluA2 subunit and are Ca2+-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.

Original languageEnglish (US)
Pages (from-to)384-392
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume56
DOIs
StatePublished - Sep 1 2013

Fingerprint

AMPA Receptors
Retinal Ganglion Cells
Glutamate Receptors
Darkness
Protein Transport
Animal Housing
Synapses
Small Interfering RNA
Proteins
Light

Keywords

  • AMPA receptor
  • Arc
  • GRIP
  • PICK1
  • Plasticity
  • Retina

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Molecular mechanisms underlying activity-dependent AMPA receptor cycling in retinal ganglion cells. / Casimiro, Tanya M.; Nawy, Scott; Carroll, Reed C.

In: Molecular and Cellular Neuroscience, Vol. 56, 01.09.2013, p. 384-392.

Research output: Contribution to journalArticle

Casimiro, Tanya M. ; Nawy, Scott ; Carroll, Reed C. / Molecular mechanisms underlying activity-dependent AMPA receptor cycling in retinal ganglion cells. In: Molecular and Cellular Neuroscience. 2013 ; Vol. 56. pp. 384-392.
@article{9f9f138aa44c4ea4935ee34086d083ae,
title = "Molecular mechanisms underlying activity-dependent AMPA receptor cycling in retinal ganglion cells",
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 Ca2+, and those that possess at least one GluA2 subunit and are Ca2+-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.",
keywords = "AMPA receptor, Arc, GRIP, PICK1, Plasticity, Retina",
author = "Casimiro, {Tanya M.} and Scott Nawy and Carroll, {Reed C.}",
year = "2013",
month = "9",
day = "1",
doi = "10.1016/j.mcn.2013.07.010",
language = "English (US)",
volume = "56",
pages = "384--392",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Molecular mechanisms underlying activity-dependent AMPA receptor cycling in retinal ganglion cells

AU - Casimiro, Tanya M.

AU - Nawy, Scott

AU - Carroll, Reed C.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - 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 Ca2+, and those that possess at least one GluA2 subunit and are Ca2+-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.

AB - 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 Ca2+, and those that possess at least one GluA2 subunit and are Ca2+-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.

KW - AMPA receptor

KW - Arc

KW - GRIP

KW - PICK1

KW - Plasticity

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=84883220058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883220058&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2013.07.010

DO - 10.1016/j.mcn.2013.07.010

M3 - Article

C2 - 23911793

AN - SCOPUS:84883220058

VL - 56

SP - 384

EP - 392

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

SN - 1044-7431

ER -