An automated platform for Assessing Working Memory and prefrontal circuit function.

Area of Science:

• Neuroscience
• Cognitive Science
• Behavioral Science

Background:

• Working memory relies on prefrontal cortex circuits, involving pyramidal neurons and interneurons.
• Chronic stress impairs working memory, but underlying neural mechanisms remain unclear.
• Existing methods lack scalability and compatibility with advanced neural recording techniques.

Purpose of the Study:

• To develop and validate a novel, automated platform for high-throughput working memory assessment.
• To enable simultaneous two-photon calcium imaging during behavioral tasks in chronic stress models.
• To facilitate research on the neural circuit disruptions caused by chronic stress.

Main Methods:

• Designed and built an inexpensive, automated, and scalable behavioral platform.
• Validated the platform using a delayed response working memory task in mice.
• Integrated two-photon calcium imaging to record from large neuronal populations.
• Developed methods to mitigate stress associated with head-fixation during imaging.

Main Results:

• Mice were trained to perform a working memory task with high fidelity within approximately 15 days.
• The platform successfully enabled large-scale neural recordings during task performance.
• Over 70% of medial prefrontal cortical neurons showed task-related activity modulation.
• A majority of recorded neurons were engaged by multiple task features.

Conclusions:

• The developed platform is effective for high-throughput, automated working memory assessment and neural recording.
• It provides a valuable tool for investigating the neural circuit basis of working memory deficits under chronic stress.
• Future research can leverage this platform to explore circuit mechanisms and therapeutic strategies for stress-induced cognitive impairments.