Deficient NRG1-ERBB signaling alters social approach: Relevance to genetic mouse models of schizophrenia

Sheryl S. Moy; H. Troy Ghashghaei; Randal J. Nonneman; Jill M. Weimer; Yukako Yokota; Daekee Lee; Cary Lai; David W. Threadgill; E. S. Anton

doi:10.1007/s11689-009-9017-8

Deficient NRG1-ERBB signaling alters social approach: Relevance to genetic mouse models of schizophrenia

Sheryl S. Moy, H. Troy Ghashghaei, Randal J. Nonneman, Jill M. Weimer, Yukako Yokota, Daekee Lee, Cary Lai, David W. Threadgill, E. S. Anton

Department of Life Science

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/-), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/- pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling.

Original language	English
Pages (from-to)	302-312
Number of pages	11
Journal	Journal of Neurodevelopmental Disorders
Volume	1
Issue number	4
DOIs	https://doi.org/10.1007/s11689-009-9017-8
State	Published - 2009

Bibliographical note

Funding Information:
Acknowledgements The authors would like to thank Dr. Ralf S. Schmid for his assistance with the Nrg1 mice. This research was supported by National Institutes for Mental Health Silvio O. Conte Center for Neuroscience of Mental Disorders grant P50 MH064065 (Project 5) to E.A., National Alliance for Research on Schizophrenia and Depression (Staglin Music Festival NARSAD Award) to E.A., National Cancer Institute grant CA092479 to D.T., National Science Foundation grant MCB-9729645 to D.T., and National Institute of Child Health and Human Development grant P30 HD03110 to Dr. Joseph Piven.

Keywords

Grin1
Growth factor
NMDA receptor
Schizophrenia
Sociability
Social novelty

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10.1007/s11689-009-9017-8

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title = "Deficient NRG1-ERBB signaling alters social approach: Relevance to genetic mouse models of schizophrenia",

abstract = "Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/-), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/- pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling.",

keywords = "Grin1, Growth factor, NMDA receptor, Schizophrenia, Sociability, Social novelty",

author = "Moy, {Sheryl S.} and Ghashghaei, {H. Troy} and Nonneman, {Randal J.} and Weimer, {Jill M.} and Yukako Yokota and Daekee Lee and Cary Lai and Threadgill, {David W.} and Anton, {E. S.}",

note = "Funding Information: Acknowledgements The authors would like to thank Dr. Ralf S. Schmid for his assistance with the Nrg1 mice. This research was supported by National Institutes for Mental Health Silvio O. Conte Center for Neuroscience of Mental Disorders grant P50 MH064065 (Project 5) to E.A., National Alliance for Research on Schizophrenia and Depression (Staglin Music Festival NARSAD Award) to E.A., National Cancer Institute grant CA092479 to D.T., National Science Foundation grant MCB-9729645 to D.T., and National Institute of Child Health and Human Development grant P30 HD03110 to Dr. Joseph Piven.",

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doi = "10.1007/s11689-009-9017-8",

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journal = "Journal of Neurodevelopmental Disorders",

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T2 - Relevance to genetic mouse models of schizophrenia

AU - Moy, Sheryl S.

AU - Ghashghaei, H. Troy

AU - Nonneman, Randal J.

AU - Weimer, Jill M.

AU - Yokota, Yukako

AU - Lee, Daekee

AU - Lai, Cary

AU - Threadgill, David W.

AU - Anton, E. S.

N1 - Funding Information: Acknowledgements The authors would like to thank Dr. Ralf S. Schmid for his assistance with the Nrg1 mice. This research was supported by National Institutes for Mental Health Silvio O. Conte Center for Neuroscience of Mental Disorders grant P50 MH064065 (Project 5) to E.A., National Alliance for Research on Schizophrenia and Depression (Staglin Music Festival NARSAD Award) to E.A., National Cancer Institute grant CA092479 to D.T., National Science Foundation grant MCB-9729645 to D.T., and National Institute of Child Health and Human Development grant P30 HD03110 to Dr. Joseph Piven.

PY - 2009

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N2 - Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/-), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/- pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling.

AB - Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/-), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/- pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling.

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IS - 4

ER -

Deficient NRG1-ERBB signaling alters social approach: Relevance to genetic mouse models of schizophrenia

Abstract

Bibliographical note

Keywords

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