Decision Making in Mice During an Optimized Touchscreen Spatial Working Memory Task Sensitive to Medial Prefrontal...

Area of Science:

• Neuroscience
• Cognitive Science
• Animal Behavior

Background:

• Working memory is crucial for decision-making and impaired in neurological diseases.
• Spatial working memory tasks in rodents help study the neurobiology of memory.
• The trial unique non-match to location (TUNL) task assesses spatial working memory and pattern separation.

Purpose of the Study:

• Optimize the TUNL task for mice to reduce training time and strategy development.
• Pharmacologically characterize the roles of the medial prefrontal cortex (mPFC) and N-methyl-D-aspartate receptors (NMDAr) in TUNL performance.

Main Methods:

• Optimized an automated touchscreen TUNL protocol for mice.
• Assessed the impact of medial prefrontal cortex (mPFC) inactivation using muscimol and baclofen.
• Administered ketamine to evaluate N-methyl-D-aspartate receptor (NMDAr) antagonist effects on working memory.

Main Results:

• Optimized TUNL protocol enabled mice to accurately perform the enhanced task.
• mPFC inactivation impaired TUNL performance in a delay-dependent manner and increased proactive interference.
• Ketamine administration caused dose- and delay-dependent working memory impairments.

Conclusions:

• The optimized TUNL task is a sensitive measure of spatial working memory in mice.
• Intact medial prefrontal cortex (mPFC) function and N-methyl-D-aspartate receptor (NMDAr) activity are essential for TUNL performance.
• This task is valuable for studying spatial working memory with genetic tools in mice.