Related Experiment Video
Updated: May 17, 2026
An Appetitive Spatial Working Memory Task for Mice in a Semi-Automated 8-Arm Radial Maze, Reducing Fearful Memory Association in the Maze
Published on: July 29, 2025
LRRTM1-deficient mice show a rare phenotype of avoiding small enclosures--a tentative mouse model for
V Voikar1,2, N Kulesskaya1,2, T Laakso1
1Neuroscience Center, University of Helsinki, Finland.
Abstract:
The LRRTM family proteins have been shown to act as synaptogenic cell adhesion molecules via interaction with presynaptic neurexins and are associated with neuropsychiatric disorders. LRRTM1-knockout mice have subtle morphological deficits in excitatory hippocampal synapses and were suggested to have impaired cognitive function. Here we report that LRRTM1-knockout mice exhibit an extraordinary phenotype of avoiding small enclosures. In the light-dark box, the knockout mice escape to dark through a standard opening as quickly as wild-type littermates but avoid escaping through a small doorway. While all wild-type mice spontaneously enter a small tube, most knockout mice do not. This apparent aversion to enter narrow space may explain other abnormalities such as increased time in open arms in the elevated plus maze and less visits through a tunnel in the IntelliCage. Moreover, LRRTM1-knockout mice show increased social interaction, reduced nest building and MK801-induced locomotion, and slower swim speed but normal water maze learning. Since LRRTM1 is predominantly expressed in thalamus, hippocampus and limbic cortex, specific synaptic defects in those areas presumably cause these behavioural abnormalities.
Insights
Mice lacking the LRRTM1 protein avoid small spaces, indicating a novel behavioral abnormality. This finding may link LRRTM1 to neuropsychiatric disorders and spatial cognition.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Genetics
Background:
- Leucine-rich repeat transmembrane protein 1 (LRRTM1) is implicated in synaptogenesis and neuropsychiatric disorders.
- LRRTM1-knockout mice previously showed subtle synaptic deficits and potential cognitive impairments.
Purpose of the Study:
- To investigate the behavioral phenotype of LRRTM1-knockout mice.
- To explore the role of LRRTM1 in spatial behavior and anxiety-related responses.
Main Methods:
- Behavioral testing in LRRTM1-knockout and wild-type mice using light-dark box, elevated plus maze, IntelliCage, and open field tests.
- Assessment of social interaction, nest building, and response to MK801 (a NMDA receptor antagonist).
Main Results:
- LRRTM1-knockout mice exhibited a strong aversion to small enclosures, avoiding narrow doorways and tunnels.
- These mice showed increased social interaction, reduced nest building, and altered MK801-induced locomotion.
- Swim speed was slower, but water maze learning remained normal, suggesting specific behavioral deficits.
Conclusions:
- LRRTM1 deficiency leads to a distinct phenotype of spatial aversion, particularly in confined spaces.
- These behavioral abnormalities are likely linked to LRRTM1's expression in the thalamus, hippocampus, and limbic cortex.
- The findings highlight LRRTM1's crucial role in regulating specific behaviors relevant to neuropsychiatric conditions.
