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Topographical memory analyzed in mice using the Hamlet test, a novel complex maze.
Lucie Crouzier1, Damien Gilabert1, Mireille Rossel1
1MMDN, Univ. Montpellier, EPHE, INSERM, UMR-S1198, PSL Research University, Montpellier F-34095, France.
Neurobiology of Learning and Memory
|February 20, 2018
Summary
The Hamlet test assesses topographical memory in mice using a complex village environment. This innovative tool reveals how training impacts memory and identifies potential therapeutic targets for conditions like Alzheimer's disease.
Area of Science:
- Neuroscience
- Animal Behavior
- Cognitive Science
Background:
- Topographical memory is crucial for spatial navigation.
- Disorientation is an early symptom of Alzheimer's disease.
- Existing models for studying topographical memory are limited.
Purpose of the Study:
- To introduce and validate the Hamlet test, a novel apparatus for assessing topographical memory in mice.
- To investigate the neural and molecular mechanisms underlying topographical memory formation and retrieval.
- To explore the utility of the Hamlet test in modeling Alzheimer's disease-related memory deficits.
Main Methods:
- Mice were trained in a complex, multi-house environment (Hamlet test) to locate reward-associated houses.
- Behavioral analysis assessed exploration patterns, memory recall after water/food deprivation, and effects of training duration/delay.
- Neuroanatomical mapping using FosB/ΔFosB immunolabelling identified activated brain regions.
- Hippocampal neurogenesis was quantified, and the effects of cholinergic antagonists were evaluated.
- Alzheimer's disease was modeled using intracerebroventricular amyloid-beta (Aβ25-35) peptide injection in trained mice.
Main Results:
- Training enhanced memory recall, with significant differences observed between mouse strains but not genders.
- The hippocampus-subiculum-parahippocampal gyrus axis and dopaminergic structures were activated during training.
- Training increased hippocampal neurogenesis and altered the effects of muscarinic/nicotinic cholinergic antagonists.
- Aβ25-35 peptide injection induced topographical memory impairment in trained mice.
Conclusions:
- The Hamlet test provides a robust platform for studying topographical memory in mice.
- The study elucidates key neural circuits and neuroplastic changes involved in spatial memory.
- The Hamlet test effectively models topographical disorientation observed in Alzheimer's disease, offering a valuable research tool.
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