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Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders

Grayton, Hannah Mary, Missler, Markus, Collier, David Andrew, Fernandes, Cathy·2013·PLoS ONE
DOI 10.1371/journal.pone.0067114PMC PMC3696036
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Figures

Figure 1 Deletion of Nrxn1α affects locomotor activity in females. Data shown are means (± sem) distance travelled by the Nrxn1α mice during the 3 one hour recordings in the homecage task. Data derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice. Activity is shown for the transfer hour (male A, female C) and dark hour (male B, female D). Data from each hour was split into six 10 min time bins. Levels of significance indicated by *** as p<0.001, compared to WT mice.
Figure 1 Deletion of Nrxn1α affects locomotor activity in females. Data shown are means (± sem) distance travelled by the Nrxn1α mice during the 3 one hour recordings in the homecage task. Data derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice. Activity is shown for the transfer hour (male A, female C) and dark hour (male B, female D). Data from each hour was split into six 10 min time bins. Levels of significance indicated by *** as p<0.001, compared to WT mice.CC BY · PubMed Central
Figure 2 Anxiety is elevated in male Nrxn1α mice. Data shown are anxiety measures taken from the open field, light/dark box and elevated plus maze. Panels are mean (± sem) time spent in the central area of the open field for male (A) and female (B) Nrxn1α mice, time spent in the light compartment of the light/dark box for male (C) and female (D) Nrxn1α mice and time spent in the open arms of the elevated plus maze for male (E) and female (F) Nrxn1α mice. Data derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice. Levels of significance indicated by *** as p<0.001, compared to WT mice, and ### as p<0.001, compared to HET mice.
Figure 2 Anxiety is elevated in male Nrxn1α mice. Data shown are anxiety measures taken from the open field, light/dark box and elevated plus maze. Panels are mean (± sem) time spent in the central area of the open field for male (A) and female (B) Nrxn1α mice, time spent in the light compartment of the light/dark box for male (C) and female (D) Nrxn1α mice and time spent in the open arms of the elevated plus maze for male (E) and female (F) Nrxn1α mice. Data derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice. Levels of significance indicated by *** as p<0.001, compared to WT mice, and ### as p<0.001, compared to HET mice.CC BY · PubMed Central
Figure 3 Deletion of Nrxn1α causes reduced locomotor activity in the light/dark box. Data shown are mean (± sem) number of transmissions between the light and dark compartments for male (A) and female (B) Nrxn1α mice. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by ** and *** as p<0.1 and p<0.001, respectively, compared to WT mice.
Figure 3 Deletion of Nrxn1α causes reduced locomotor activity in the light/dark box. Data shown are mean (± sem) number of transmissions between the light and dark compartments for male (A) and female (B) Nrxn1α mice. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by ** and *** as p<0.1 and p<0.001, respectively, compared to WT mice.CC BY · PubMed Central
Figure 4 Deletion of Nrxn1α affects the social approach behaviours in mice. Data shown are social approach behaviours of the Nrxn1α mice during the three-chamber social approach task. A – Trial 1 - Mean (± sem) time spent (s) in the chamber containing the mouse, the centre chamber or the chamber containing the object. B – Trial 2 - Mean (± sem) time spent (s) in the chamber containing the familiar mouse, the centre chamber or the chamber containing the novel mouse. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by ** and *** as p<0.01 and p<0.001, respectively, compared to WT mice, and ## and ### as p<0.01 and p<0.001, respectively, compared to HET mice.
Figure 4 Deletion of Nrxn1α affects the social approach behaviours in mice. Data shown are social approach behaviours of the Nrxn1α mice during the three-chamber social approach task. A – Trial 1 - Mean (± sem) time spent (s) in the chamber containing the mouse, the centre chamber or the chamber containing the object. B – Trial 2 - Mean (± sem) time spent (s) in the chamber containing the familiar mouse, the centre chamber or the chamber containing the novel mouse. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by ** and *** as p<0.01 and p<0.001, respectively, compared to WT mice, and ## and ### as p<0.01 and p<0.001, respectively, compared to HET mice.CC BY · PubMed Central
Figure 5 Male Nrxn1α mice show increased aggressive behaviours and social investigation towards a juvenile conspecific. Data shown are the mean (± sem) social investigation behaviours of the Nrxn1α mice. A - Time spent (s) carrying out aggressive behaviours towards the juvenile conspecific by the male Nrxn1α mice in the main study. B - Time spent (s) carrying out aggressive behaviours towards the juvenile conspecific by the male Nrxn1α mice in the replication study. Time spent (s) carrying out social sniffing of the juvenile conspecific mice by the male (C) and female (E) Nrxn1α mice in the main study. Time spent (s) carrying out social sniffing of the juvenile conspecific mice by the male (D) and female (F) Nrxn1α mice in the replication study. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice for the main study, and 16 WT (7M, 9F) 12 HET (6M, 6F) 13 KO (8M, 5F) mice in the replication study, and levels of significance indicated by * and ** as p<0.05 and p<0.01, respectively, compared to WT mice, and # and ## as p<0.05 and p<0.01, respectively, compared to HET mice.
Figure 5 Male Nrxn1α mice show increased aggressive behaviours and social investigation towards a juvenile conspecific. Data shown are the mean (± sem) social investigation behaviours of the Nrxn1α mice. A - Time spent (s) carrying out aggressive behaviours towards the juvenile conspecific by the male Nrxn1α mice in the main study. B - Time spent (s) carrying out aggressive behaviours towards the juvenile conspecific by the male Nrxn1α mice in the replication study. Time spent (s) carrying out social sniffing of the juvenile conspecific mice by the male (C) and female (E) Nrxn1α mice in the main study. Time spent (s) carrying out social sniffing of the juvenile conspecific mice by the male (D) and female (F) Nrxn1α mice in the replication study. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice for the main study, and 16 WT (7M, 9F) 12 HET (6M, 6F) 13 KO (8M, 5F) mice in the replication study, and levels of significance indicated by * and ** as p<0.05 and p<0.01, respectively, compared to WT mice, and # and ## as p<0.05 and p<0.01, respectively, compared to HET mice.CC BY · PubMed Central
Figure 6 Impairment in nest building behaviours in the Nrxn1α KO mouse. Data shown are the mean (± sem) weight (g) of the nests built by the mice over a 24 hour period. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by *** as p<0.0001, compared to WT mice, and ## and ### as p<0.01 and p<0.001, respectively, compared to HET mice.
Figure 6 Impairment in nest building behaviours in the Nrxn1α KO mouse. Data shown are the mean (± sem) weight (g) of the nests built by the mice over a 24 hour period. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by *** as p<0.0001, compared to WT mice, and ## and ### as p<0.01 and p<0.001, respectively, compared to HET mice.CC BY · PubMed Central
Figure 7 Nrxn1α mice show no impairment in spatial working. Data shown are mean (± sem) behaviours of the Nrxn1α mice during the Morris water maze. Latency to reach the platform for male (A) and female (B) mice, path length for male (C) and female (D) mice, and swim speed for male (E) and female (F) mice. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by ** and *** as p<0.01 and p<0.0001, respectably, compared to WT mice.
Figure 7 Nrxn1α mice show no impairment in spatial working. Data shown are mean (± sem) behaviours of the Nrxn1α mice during the Morris water maze. Latency to reach the platform for male (A) and female (B) mice, path length for male (C) and female (D) mice, and swim speed for male (E) and female (F) mice. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by ** and *** as p<0.01 and p<0.0001, respectably, compared to WT mice.CC BY · PubMed Central
Figure 8 Nrxn1α mice show no impairment in working/episodic memory. Data shown are mean (± sem) behaviours of the Nrxn1α mice during the delayed matching-to-place task. Latency to reach the platform for male (A) and female (B) mice, path length for male (C) and female (D) mice and swim speed for male (E) and female (F) mice. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by * as p<0.05, compared to WT mice, and # as p<0.05, compared to HET mice.
Figure 8 Nrxn1α mice show no impairment in working/episodic memory. Data shown are mean (± sem) behaviours of the Nrxn1α mice during the delayed matching-to-place task. Latency to reach the platform for male (A) and female (B) mice, path length for male (C) and female (D) mice and swim speed for male (E) and female (F) mice. Data is derived from 23 WT (12M, 11F) 29 HET (15M, 14F) 18 KO (9M, 9F) mice, and levels of significance indicated by * as p<0.05, compared to WT mice, and # as p<0.05, compared to HET mice.CC BY · PubMed Central

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Cites

Show all 17 references

Research works printed but not linked: 21

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  2. G Kattenstroth, 2004, Postsynaptic N-methyl-D-aspartate receptor function requires alpha-neurexins. Proceedings of the National Academy of Sciences of the United States of America, 101, 2607
  3. W Zhang, 2005, Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels. The Journal of neuroscience : the official journal of the Society for Neuroscience, 25, 4330
  4. I Dudanova, 2006, Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of secretory granules. The Journal of neuroscience : the official journal of the Society for Neuroscience, 26, 10599
  5. J Feng, 2006, High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neuroscience letters, 409, 10
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  18. Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, et al.. (2013) Deficiency of Schnurri-2, an MHC Enhancer Binding Protein, Induces Mild Chronic Inflammation in the Brain and Confers Molecular, Neuronal, and Behavioral Phenotypes Related to Schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. · DOI · Paper page
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Metadata

Authors
Grayton, H. M., Missler, M., Collier, D. A., & Fernandes, C.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-06-28
Volume
8
Issue
6
Pages
e67114
ISSN
1932-6203
DOI
10.1371/journal.pone.0067114
PMC
PMC3696036
Cited by
180
References
17
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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Grayton, H. M., Missler, M., Collier, D. A., & Fernandes, C. (2013). Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders. PLoS ONE. https://doi.org/10.1371/journal.pone.0067114

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