Deletion of Nrxn1α affects the social approach behaviours in mice.

<p>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.</p

Nrxn1α mice show no impairment in spatial working.

<p>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.</p

Anxiety is elevated in male Nrxn1α mice.

<p>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.</p

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

<div><p>Background</p><p>Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α) knockout (KO) mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism.</p><p>Methods</p><p>We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J<b>)</b> to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9–16 per genotype, per sex).</p><p>Results</p><p>In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours.</p><p>Conclusions</p><p>These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder.</p></div

Deletion of Nrxn1α causes reduced locomotor activity in the light/dark box.

<p>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.</p

Deletion of Nrxn1α affects locomotor activity in females.

<p>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.</p

Impairment in nest building behaviours in the Nrxn1α KO mouse.

<p>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.</p

Male Nrxn1α mice show increased aggressive behaviours and social investigation towards a juvenile conspecific.

<p>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.</p

Medical imaging training with eye movement modeling examples: A randomized controlled study

To determine whether ultrasound training in which the expert’s eye movements are superimposed to the underlying ultrasound video (eye movement modeling examples; EMMEs) leads to better learner outcomes than traditional eye movement-free instructions. 106 undergraduate medical students were randomized in two groups; 51 students in the EMME group watched 5-min ultrasound examination videos combined with the eye movements of an expert performing the task. The identical videos without the eye movements were shown to 55 students in the control group. Performance and behavioral parameters were compared prepost interventional using ANOVAs. Additionally, cognitive load, and prior knowledge in anatomy were surveyed. After training, the EMME group identified more sonoanatomical structures correctly, and completed the tasks faster than the control group. This effect was partly mediated by a reduction of extraneous cognitive load. Participants with greater prior anatomical knowledge benefited the most from the EMME training. Displaying experts’ eye movements in medical imaging training appears to be an effective way to foster medical interpretation skills of undergraduate medical students. One underlying mechanism might be that practicing with eye movements reduces cognitive load and helps learners activate their prior knowledge.</p