Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2

J. Blundell, K. Tabuchi, M. F. Bolliger, C. A. Blaiss, N. Brose, X. Liu, T. C. Südhof, C. M. Powell

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Neuroligins (NL) are postsynaptic cell adhesion molecules that are thought to specify synapse properties. Previous studies showed that mutant mice carrying an autism-associated point mutation in NL3 exhibit social interaction deficits, enhanced inhibitory synaptic function and increased staining of inhibitory synaptic puncta without changes in overall inhibitory synapse numbers. In contrast, mutant mice lacking NL2 displayed decreased inhibitory synaptic function. These studies raised two relevant questions. First, does NL2 deletion impair inhibitory synaptic function by altering the number of inhibitory synapses, or by changing their efficacy? Second, does this effect of NL2 deletion on inhibition produce behavioral changes? We now show that although NL2-deficient mice exhibit an apparent decrease in number of inhibitory synaptic puncta, the number of symmetric synapses as determined by electron microscopy is unaltered, suggesting that NL2 deletion impairs the function of inhibitory synapses without decreasing their numbers. This decrease in inhibitory synaptic function in NL2-deficient mice correlates with a discrete behavioral phenotype that includes a marked increase in anxiety-like behavior, a decrease in pain sensitivity and a slight decrease in motor co-ordination. This work confirms that NL2 modulates inhibitory synaptic function and is the first demonstration that global deletion of NL2 can lead to a selective behavioral phenotype.

Original languageEnglish (US)
Pages (from-to)114-126
Number of pages13
JournalGenes, Brain and Behavior
Volume8
Issue number1
DOIs
StatePublished - Feb 2009

Fingerprint

Cell Adhesion Molecules
Synapses
Anxiety
Phenotype
Interpersonal Relations
Autistic Disorder
Point Mutation
Electron Microscopy
neuroligin 2
Staining and Labeling
Pain

Keywords

  • Anxiety
  • Autism
  • GABA
  • Inhibition
  • Neurexin
  • Neuroligin
  • Nociception
  • Pain
  • Social interaction

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Blundell, J., Tabuchi, K., Bolliger, M. F., Blaiss, C. A., Brose, N., Liu, X., ... Powell, C. M. (2009). Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2. Genes, Brain and Behavior, 8(1), 114-126. https://doi.org/10.1111/j.1601-183X.2008.00455.x

Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2. / Blundell, J.; Tabuchi, K.; Bolliger, M. F.; Blaiss, C. A.; Brose, N.; Liu, X.; Südhof, T. C.; Powell, C. M.

In: Genes, Brain and Behavior, Vol. 8, No. 1, 02.2009, p. 114-126.

Research output: Contribution to journalArticle

Blundell, J, Tabuchi, K, Bolliger, MF, Blaiss, CA, Brose, N, Liu, X, Südhof, TC & Powell, CM 2009, 'Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2', Genes, Brain and Behavior, vol. 8, no. 1, pp. 114-126. https://doi.org/10.1111/j.1601-183X.2008.00455.x
Blundell, J. ; Tabuchi, K. ; Bolliger, M. F. ; Blaiss, C. A. ; Brose, N. ; Liu, X. ; Südhof, T. C. ; Powell, C. M. / Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2. In: Genes, Brain and Behavior. 2009 ; Vol. 8, No. 1. pp. 114-126.
@article{0d017c3960ff459a8360898b5c313866,
title = "Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2",
abstract = "Neuroligins (NL) are postsynaptic cell adhesion molecules that are thought to specify synapse properties. Previous studies showed that mutant mice carrying an autism-associated point mutation in NL3 exhibit social interaction deficits, enhanced inhibitory synaptic function and increased staining of inhibitory synaptic puncta without changes in overall inhibitory synapse numbers. In contrast, mutant mice lacking NL2 displayed decreased inhibitory synaptic function. These studies raised two relevant questions. First, does NL2 deletion impair inhibitory synaptic function by altering the number of inhibitory synapses, or by changing their efficacy? Second, does this effect of NL2 deletion on inhibition produce behavioral changes? We now show that although NL2-deficient mice exhibit an apparent decrease in number of inhibitory synaptic puncta, the number of symmetric synapses as determined by electron microscopy is unaltered, suggesting that NL2 deletion impairs the function of inhibitory synapses without decreasing their numbers. This decrease in inhibitory synaptic function in NL2-deficient mice correlates with a discrete behavioral phenotype that includes a marked increase in anxiety-like behavior, a decrease in pain sensitivity and a slight decrease in motor co-ordination. This work confirms that NL2 modulates inhibitory synaptic function and is the first demonstration that global deletion of NL2 can lead to a selective behavioral phenotype.",
keywords = "Anxiety, Autism, GABA, Inhibition, Neurexin, Neuroligin, Nociception, Pain, Social interaction",
author = "J. Blundell and K. Tabuchi and Bolliger, {M. F.} and Blaiss, {C. A.} and N. Brose and X. Liu and S{\"u}dhof, {T. C.} and Powell, {C. M.}",
year = "2009",
month = "2",
doi = "10.1111/j.1601-183X.2008.00455.x",
language = "English (US)",
volume = "8",
pages = "114--126",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2

AU - Blundell, J.

AU - Tabuchi, K.

AU - Bolliger, M. F.

AU - Blaiss, C. A.

AU - Brose, N.

AU - Liu, X.

AU - Südhof, T. C.

AU - Powell, C. M.

PY - 2009/2

Y1 - 2009/2

N2 - Neuroligins (NL) are postsynaptic cell adhesion molecules that are thought to specify synapse properties. Previous studies showed that mutant mice carrying an autism-associated point mutation in NL3 exhibit social interaction deficits, enhanced inhibitory synaptic function and increased staining of inhibitory synaptic puncta without changes in overall inhibitory synapse numbers. In contrast, mutant mice lacking NL2 displayed decreased inhibitory synaptic function. These studies raised two relevant questions. First, does NL2 deletion impair inhibitory synaptic function by altering the number of inhibitory synapses, or by changing their efficacy? Second, does this effect of NL2 deletion on inhibition produce behavioral changes? We now show that although NL2-deficient mice exhibit an apparent decrease in number of inhibitory synaptic puncta, the number of symmetric synapses as determined by electron microscopy is unaltered, suggesting that NL2 deletion impairs the function of inhibitory synapses without decreasing their numbers. This decrease in inhibitory synaptic function in NL2-deficient mice correlates with a discrete behavioral phenotype that includes a marked increase in anxiety-like behavior, a decrease in pain sensitivity and a slight decrease in motor co-ordination. This work confirms that NL2 modulates inhibitory synaptic function and is the first demonstration that global deletion of NL2 can lead to a selective behavioral phenotype.

AB - Neuroligins (NL) are postsynaptic cell adhesion molecules that are thought to specify synapse properties. Previous studies showed that mutant mice carrying an autism-associated point mutation in NL3 exhibit social interaction deficits, enhanced inhibitory synaptic function and increased staining of inhibitory synaptic puncta without changes in overall inhibitory synapse numbers. In contrast, mutant mice lacking NL2 displayed decreased inhibitory synaptic function. These studies raised two relevant questions. First, does NL2 deletion impair inhibitory synaptic function by altering the number of inhibitory synapses, or by changing their efficacy? Second, does this effect of NL2 deletion on inhibition produce behavioral changes? We now show that although NL2-deficient mice exhibit an apparent decrease in number of inhibitory synaptic puncta, the number of symmetric synapses as determined by electron microscopy is unaltered, suggesting that NL2 deletion impairs the function of inhibitory synapses without decreasing their numbers. This decrease in inhibitory synaptic function in NL2-deficient mice correlates with a discrete behavioral phenotype that includes a marked increase in anxiety-like behavior, a decrease in pain sensitivity and a slight decrease in motor co-ordination. This work confirms that NL2 modulates inhibitory synaptic function and is the first demonstration that global deletion of NL2 can lead to a selective behavioral phenotype.

KW - Anxiety

KW - Autism

KW - GABA

KW - Inhibition

KW - Neurexin

KW - Neuroligin

KW - Nociception

KW - Pain

KW - Social interaction

UR - http://www.scopus.com/inward/record.url?scp=59149088359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59149088359&partnerID=8YFLogxK

U2 - 10.1111/j.1601-183X.2008.00455.x

DO - 10.1111/j.1601-183X.2008.00455.x

M3 - Article

C2 - 19016888

AN - SCOPUS:59149088359

VL - 8

SP - 114

EP - 126

JO - Genes, Brain and Behavior

JF - Genes, Brain and Behavior

SN - 1601-1848

IS - 1

ER -