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Loss of EphA4 impairs short-term spatial recognition memory performance and locomotor habituation


Willi, R; Winter, C; Wieske, F; Kempf, A; Yee, B; Schwab, M E; Singer, P (2012). Loss of EphA4 impairs short-term spatial recognition memory performance and locomotor habituation. Genes, Brain and Behavior, 11(8):1020-1031.

Abstract

EphA4 receptor (EphA4) tyrosine kinase is an important regulator of central nervous system development and synaptic plasticity in the mature brain, but its relevance to the control of normal behavior remains largely unexplored. This study is the first attempt to obtain a behavioral profile of constitutive homozygous and heterozygous EphA4 knockout mice. A deficit in locomotor habituation in the open field, impairment in spatial recognition in the Y-maze and reduced probability of spatial spontaneous alternation in the T-maze were identified in homozygous EphA4(-/-) mice, while heterozygo us EphA4(+/-) mice appeared normal on these tests in comparison with wild-type (WT) controls. The multiple phenotypes observed in EphA4(-/-) mice might stem from an underlying deficit in habituation learning, reflecting an elementary form of nonassociative learning that is in contrast to Pavlovian associative learning, which appeared unaffected by EphA4 disruption. A deficit in motor coordination on the accelerating rotarod was also demonstrated only in EphA4(-/-) mice - a finding in keeping with the presence of abnormal gait in EphA4(-/-) mice - although they were able to improve performance over training. There was no evidence for substantial changes in major neurochemical markers in various brain regions rich in EphA4 as shown by post-mortem analysis. This excludes the possibility of major neurochemical compensation in the brain of EphA4(-/-) mice. In summary, we have demonstrated for the first time the behavioral significance of EphA4 disruption, supporting further investigation of EphA4 as a possible target for behavioral interventions where habituation deficits are prominent.

Abstract

EphA4 receptor (EphA4) tyrosine kinase is an important regulator of central nervous system development and synaptic plasticity in the mature brain, but its relevance to the control of normal behavior remains largely unexplored. This study is the first attempt to obtain a behavioral profile of constitutive homozygous and heterozygous EphA4 knockout mice. A deficit in locomotor habituation in the open field, impairment in spatial recognition in the Y-maze and reduced probability of spatial spontaneous alternation in the T-maze were identified in homozygous EphA4(-/-) mice, while heterozygo us EphA4(+/-) mice appeared normal on these tests in comparison with wild-type (WT) controls. The multiple phenotypes observed in EphA4(-/-) mice might stem from an underlying deficit in habituation learning, reflecting an elementary form of nonassociative learning that is in contrast to Pavlovian associative learning, which appeared unaffected by EphA4 disruption. A deficit in motor coordination on the accelerating rotarod was also demonstrated only in EphA4(-/-) mice - a finding in keeping with the presence of abnormal gait in EphA4(-/-) mice - although they were able to improve performance over training. There was no evidence for substantial changes in major neurochemical markers in various brain regions rich in EphA4 as shown by post-mortem analysis. This excludes the possibility of major neurochemical compensation in the brain of EphA4(-/-) mice. In summary, we have demonstrated for the first time the behavioral significance of EphA4 disruption, supporting further investigation of EphA4 as a possible target for behavioral interventions where habituation deficits are prominent.

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7 citations in Web of Science®
5 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:06 Feb 2013 16:38
Last Modified:18 Apr 2016 07:01
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1601-183X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/j.1601-183X.2012.00842.x
PubMed ID:22938696

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