Operant Assessment of DMTP Spatial Working Memory in Mice

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Cognitive Science

Background:

• Working memory (WM) is crucial for linking perception to action.
• Impaired WM is common in mental health disorders, necessitating better rodent models.
• Existing rodent WM tests can be confounded by attention or strategy confounds.

Purpose of the Study:

• To develop and validate a novel operant spatial working memory (SWM) paradigm for mice.
• To assess the feasibility of back-translating human WM tests into mouse models.
• To investigate the effects of modafinil and guanfacine on SWM performance in mice.

Main Methods:

• Mice were trained on a 5-choice based operant testing of SWM (5-CSWM) task, a delayed-matching-to-position (DMTP) paradigm.
• Training involved approximately 3 months in a non-illuminated operant box.
• Performance was assessed across varying delay intervals, and drug effects (modafinil, guanfacine) were evaluated.

Main Results:

• Mice successfully acquired the DMTP 5-CSWM task, achieving over 70% accuracy with short (2s) delays.
• Performance declined with longer delays, consistent with WM principles.
• Modafinil and guanfacine did not consistently enhance task performance.
• Mice did not improve beyond chance in a delayed non-matching-to-position (DNMTP) version of the task.

Conclusions:

• The DMTP 5-CSWM paradigm is a viable method for assessing spatial WM in mice.
• This paradigm offers high control over confounding factors like attention and motivation.
• Further research is needed to understand WM deficits and potential therapeutic targets in mouse models.