SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

Lucas Matt, Lyndsey M. Kirk, George Chenaux, David J. Speca, Kyle R. Puhger, Michael C. Pride, Mohammad Qneibi, Tomer Haham, Kristopher E. Plambeck, Yael Stern-Bach, Jill L Silverman, Jacqueline Crawley, Johannes W Hell, Elva D Diaz

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity. Matt et al. show that mice lacking the AMPAR-associated protein SynDIG4/Prrt1 display deficits in synaptic plasticity and cognition. SynDIG4 modifies AMPAR biophysical properties in heterologous cells, but synaptic AMPAR kinetics are unchanged, suggesting that SynDIG4 establishes a pool of extrasynaptic AMPARs necessary for higher-order cognitive plasticity.

Original languageEnglish (US)
Pages (from-to)2455-2468
Number of pages14
JournalCell Reports
Volume22
Issue number9
DOIs
StatePublished - Feb 27 2018

Fingerprint

AMPA Receptors
Synapses
Cognition
Plasticity
Knockout Mice
Electrophysiology
Proteins
Neurotransmitter Receptor
Neuronal Plasticity
Long-Term Potentiation
Tetanus
Assays
Genes
Immunohistochemistry
Display devices
Learning
Data storage equipment
Kinetics

Keywords

  • auxiliary factor
  • excitatory synapse
  • extrasynaptic AMPARs
  • hippocampus
  • LTP
  • NG5
  • Prrt1
  • SynDIG family
  • SynDIG4

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function. / Matt, Lucas; Kirk, Lyndsey M.; Chenaux, George; Speca, David J.; Puhger, Kyle R.; Pride, Michael C.; Qneibi, Mohammad; Haham, Tomer; Plambeck, Kristopher E.; Stern-Bach, Yael; Silverman, Jill L; Crawley, Jacqueline; Hell, Johannes W; Diaz, Elva D.

In: Cell Reports, Vol. 22, No. 9, 27.02.2018, p. 2455-2468.

Research output: Contribution to journalArticle

Matt, L, Kirk, LM, Chenaux, G, Speca, DJ, Puhger, KR, Pride, MC, Qneibi, M, Haham, T, Plambeck, KE, Stern-Bach, Y, Silverman, JL, Crawley, J, Hell, JW & Diaz, ED 2018, 'SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function', Cell Reports, vol. 22, no. 9, pp. 2455-2468. https://doi.org/10.1016/j.celrep.2018.02.026
Matt, Lucas ; Kirk, Lyndsey M. ; Chenaux, George ; Speca, David J. ; Puhger, Kyle R. ; Pride, Michael C. ; Qneibi, Mohammad ; Haham, Tomer ; Plambeck, Kristopher E. ; Stern-Bach, Yael ; Silverman, Jill L ; Crawley, Jacqueline ; Hell, Johannes W ; Diaz, Elva D. / SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function. In: Cell Reports. 2018 ; Vol. 22, No. 9. pp. 2455-2468.
@article{50ec356436fb438ba863ac582d0674e6,
title = "SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function",
abstract = "Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25{\%}. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity. Matt et al. show that mice lacking the AMPAR-associated protein SynDIG4/Prrt1 display deficits in synaptic plasticity and cognition. SynDIG4 modifies AMPAR biophysical properties in heterologous cells, but synaptic AMPAR kinetics are unchanged, suggesting that SynDIG4 establishes a pool of extrasynaptic AMPARs necessary for higher-order cognitive plasticity.",
keywords = "auxiliary factor, excitatory synapse, extrasynaptic AMPARs, hippocampus, LTP, NG5, Prrt1, SynDIG family, SynDIG4",
author = "Lucas Matt and Kirk, {Lyndsey M.} and George Chenaux and Speca, {David J.} and Puhger, {Kyle R.} and Pride, {Michael C.} and Mohammad Qneibi and Tomer Haham and Plambeck, {Kristopher E.} and Yael Stern-Bach and Silverman, {Jill L} and Jacqueline Crawley and Hell, {Johannes W} and Diaz, {Elva D}",
year = "2018",
month = "2",
day = "27",
doi = "10.1016/j.celrep.2018.02.026",
language = "English (US)",
volume = "22",
pages = "2455--2468",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",

}

TY - JOUR

T1 - SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

AU - Matt, Lucas

AU - Kirk, Lyndsey M.

AU - Chenaux, George

AU - Speca, David J.

AU - Puhger, Kyle R.

AU - Pride, Michael C.

AU - Qneibi, Mohammad

AU - Haham, Tomer

AU - Plambeck, Kristopher E.

AU - Stern-Bach, Yael

AU - Silverman, Jill L

AU - Crawley, Jacqueline

AU - Hell, Johannes W

AU - Diaz, Elva D

PY - 2018/2/27

Y1 - 2018/2/27

N2 - Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity. Matt et al. show that mice lacking the AMPAR-associated protein SynDIG4/Prrt1 display deficits in synaptic plasticity and cognition. SynDIG4 modifies AMPAR biophysical properties in heterologous cells, but synaptic AMPAR kinetics are unchanged, suggesting that SynDIG4 establishes a pool of extrasynaptic AMPARs necessary for higher-order cognitive plasticity.

AB - Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity. Matt et al. show that mice lacking the AMPAR-associated protein SynDIG4/Prrt1 display deficits in synaptic plasticity and cognition. SynDIG4 modifies AMPAR biophysical properties in heterologous cells, but synaptic AMPAR kinetics are unchanged, suggesting that SynDIG4 establishes a pool of extrasynaptic AMPARs necessary for higher-order cognitive plasticity.

KW - auxiliary factor

KW - excitatory synapse

KW - extrasynaptic AMPARs

KW - hippocampus

KW - LTP

KW - NG5

KW - Prrt1

KW - SynDIG family

KW - SynDIG4

UR - http://www.scopus.com/inward/record.url?scp=85042590707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042590707&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.02.026

DO - 10.1016/j.celrep.2018.02.026

M3 - Article

C2 - 29490264

AN - SCOPUS:85042590707

VL - 22

SP - 2455

EP - 2468

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 9

ER -