IMPC: Cognitive and ethological characterisation of mice lacking melatonin MT2 receptors
Lead Research Organisation:
University of Glasgow
Department Name: School of Psychology
Abstract
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Technical Summary
Melatonin is a hormone made by a small gland at the base of the brain, which regulates sleep/wake patterns and circadian rhythms. Apart from these well-characterised roles, melatonin also acts in poorly-understood ways to affect cognitive processes such as alertness, and to modulate the brain circuitry underlying psychiatric diseases such as depression, schizophrenia and bipolar disorder. This project will perform an initial characterisation of mice lacking one of the proteins through which melatonin exerts its actions on brain cells, known as the melatonin MT2 receptor. Mice lacking the melatonin MT2 receptor appear perfectly normal, although there is some evidence to suggest that their sleeping patterns may be slightly disturbed, and that they may have some memory deficits in simple tests. The study will examine a) whether their daily activity and sleeping patterns differ from normal mice; b) the extent to which their brain chemistry is altered in the circuitry associated with psychiatric diseases such as depression, schizophrenia and bipolar disorder; and c) whether they have impaired performance in a cognitive task closely related to that used in human clinical studies - where the mice can select a series of responses using a touchscreen, and hence demonstrate their ability to sustain attention. The results will reveal the extent to which loss of melatonin's effects on the MT2 receptor may contribute to deficits in wakefulness and alertness, and to susceptibility to psychiatric disease. This will set the stage for future more detailed characterisation of the physiological and pathological function of MT2 receptors, and is likely to illuminate the exploitation of MT2 receptors as a target for current and future psychiatric drug development. In addition, if the specific circuitry associated with affective/psychotic diseases is compromised in these mice, the information will open a new avenue to studying treatment strategies aimed at normalising functional activity in this network.
People |
ORCID iD |
Brian Morris (Principal Investigator) | |
Judith Pratt (Co-Investigator) |
Publications
Thomson D
(2021)
Mice lacking melatonin MT2 receptors exhibit attentional deficits, anxiety and enhanced social interaction
in Journal of Psychopharmacology
Openshaw RL
(2019)
JNK signalling mediates aspects of maternal immune activation: importance of maternal genotype in relation to schizophrenia risk.
in Journal of neuroinflammation
Title | 24h home cage behavioural monitoring |
Description | Behavioural monitoring of mice is conducted over a 24h period in the home cage. A subcutaneous radiofrequency identification (RFID) transponder measures various parameters of activity and behaviour of group-housed mice. An infrared high-definition camera acquires video of the cage. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | The ability to conduct 24h home cage behavioural monitoring of mouse behaviour represents a substantial step forward in analysis of behaviours, both physiological and pathological. The use of the home cage reduces stress of the procedure, benefiting the animals and allowing otherwise undetectable normal behaviours to be monitored. The 24h monitoring provides a step change in sensitivity of the measurements, allowing a reduction in animal numbers. We hope to establish this technique at Glasgow University now, having performed through collaboration as part of this project. |
Title | MTNR1b knockout mice |
Description | Characterisation of mice with a genetic deletion of the type 2 melatonin receptor. Results are anticipated to reveal that this strain of mice has considerable impact for future studies on sleep regulation and psychiatric disease |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Results are anticipated to reveal that this strain of mice has considerable impact for future studies on sleep regulation and psychiatric disease |
URL | https://www.komp.org/geneinfo.php?geneid=69718 |
Description | Collaboration for behavioural testing |
Organisation | University of Strathclyde |
Department | Strathclyde Institute of Pharmacy & Biomedical Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Through a collaboration with the University of Strathclyde, we were able to conduct a series of behavioural tests that revealed some important new insights. The Institute at Strathclyde has state-of-the-art equipment for these studies, that would not have been possible at our own institution. |
Collaborator Contribution | They provided the equipment and the expertise to train the PhD student in the technques. |
Impact | Openshaw et al., Psychopharmacology, 2017, and further publications in preparation. |
Start Year | 2013 |
Description | Neurodome |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Public event at the Glasgow Science Centre planetarium, exploring and explaining the workings of the brain using the planetarium software Neurodome. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.glasgowsciencecentre.org/whats-on/question-perception-neurodome |
Description | Pint of Science |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Public event to increase awareness of recent advances in neuroscience |
Year(s) Of Engagement Activity | 2018 |
URL | https://pintofscience.co.uk/event/curing-the-brain |